Patients with\u00a0<\/span>IDH<\/em>m R\/R AML are usually not eligible for intensive chemotherapy which was the only curative treatment until recently. The development of targeted therapies, such as IDH or FLT3 inhibitors, provides new therapeutic options for these patients.<\/p>\n

As a proof of concept, the inhibition of mIDH with small-molecule selective inhibitors decreases intracellular D-2HG levels, reverses epigenetic deregulation and releases the differentiation block\u00a0in vitro<\/em>\u00a0and\u00a0in vivo<\/em>\u00a0in preclinical studies, leading to the clinical development of mIDH inhibitors.^{37,56,90\u201395<\/sup><\/span><\/p>\n}

The first IDH1 inhibitor developed on a clinical level is ivosidenib^{<\/sup>. In the\u00a0AG120-C-001\u00a0<\/span><\/span>phase I study (Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation<\/span>; ClinicalTrials.gov identifier: NCT02074839), 125 patients with an R\/R AML received ivosidenib 500 mg daily.^{96<\/sup><\/span>\u00a0Overall response rate (ORR), CR\/complete remission with incomplete haematological recovery (CRh) and CR were, respectively, 41.6, 30.4 and 21.6%. The median time to CR was 2.8 months. The overall survival (OS) after a median follow-up of 14.8 months was 8.8 months (Table 1<\/em><\/span>).^{96\u201398<\/sup><\/span>\u00a0The\u00a0a<\/span>chievement of CR\/CRh was significantly associated with a lower co-mutational burden and the absence of mutations in signalling pathways. The D-2HG level has been normalized in almost all cases, consequently being unreliable as a surrogate marker of efficacy.^{99,100<\/sup><\/span>\u00a0Thirty-four patients with ND AML who were ineligible for standard induction chemotherapy also received ivosidenib monotherapy. Frontline treatment leads to ORR, CR and CR\/CRh of 54.5, 30.3 and 42.4%, respectively. With a median follow-up of 23.5 months, the median OS was 12.6 months with an estimated 1-year OS rate of 51.1%. Again, no single-gene mutation was significantly associated with CR\/CRh.^{101<\/sup><\/span>\u00a0In the phase III AGILE trial (Study of AG-120 (ivosidenib) vs. placebo in combination with azacitidine in participants with previously untreated acute myeloid leukemia with an IDH1 mutation<\/span>; ClinicalTrials.gov identifier: NCT03173248), patients with treatment-naive AML unfit for intensive induction chemotherapy were randomly assigned to receive azacitidine and ivosidenib or matched placebo.^{102\u2013104<\/sup><\/span>\u00a0The combination therapy with ivosidenib demonstrates a high ORR of 62.5%, including 47.2% of the CR rate, versus 18.9 and 14.9% in the placebo arm (p<\/span><\/span><\/span><\/em><0.0001 and\u00a0p<\/span><\/span><0.0001), respectively. Responses were seen across cytogenetic risk groups and mutations.^{105<\/sup><\/span>\u00a0The combination of ivosidenib and azacitidine had a favourable safety profile with fewer infections (28.2%) relative to the placebo plus azacitidine arm (49.3%). The median OS for responders was 29.3 versus 7.9 months in the placebo arm (p<\/span><\/span><\/span><\/em>=0.001). The combination is approved by the FDA and\u00a0European Medicines Agency<\/span>.<\/p>\n}}}}}}}

\n
Table 1: <\/span>Efficacy and safety data of phase I\/II trials of ivosidenib and olutasidenib in relapsed\/refractory acute myeloid leukaemia^{96\u201398<\/sup><\/span><\/p>\n}
\n\n\n\n\n\n\n\n\n\n
\n
Study details<\/b><\/p>\n<\/td>\n<\/tr>\n
\n
Author (year)<\/b><\/p>\n<\/td>\n
\n
Di Nardo (2018)^{96<\/sup><\/span><\/b><\/p>\n<\/td>\n}
\n
Watts, 2023^{97<\/sup><\/span><\/b><\/p>\n<\/td>\n}
\n
De Botton, 2023^{98<\/sup><\/span><\/b><\/p>\n<\/td>\n}
\n
Watts, 2023^{97<\/sup><\/span><\/b><\/p>\n<\/td>\n<\/tr>\n}
\n
Trial name<\/b><\/p>\n<\/td>\n
\n
AG120-C-001\u00a0<\/span><\/span>study<\/p>\n<\/td>\n
\n
2102-HEM-101 study<\/p>\n<\/td>\n
\n
2102-HEM-101 study<\/p>\n<\/td>\n
\n
2102-HEM-101 study<\/p>\n<\/td>\n<\/tr>\n
\n
ClinicalTrials.gov identifier<\/b><\/p>\n<\/td>\n
\n
NCT02074839<\/p>\n<\/td>\n
\n
NCT02719574<\/p>\n<\/td>\n
\n
NCT02719574<\/p>\n<\/td>\n
\n
NCT02719574<\/p>\n<\/td>\n<\/tr>\n
\n
Phase<\/b><\/p>\n<\/td>\n
\n
Phase I<\/p>\n<\/td>\n
\n
Phase I<\/p>\n<\/td>\n
\n
Phase II<\/p>\n<\/td>\n
\n
Phase I<\/p>\n<\/td>\n<\/tr>\n
\n
Treatment<\/b><\/p>\n<\/td>\n
\n
Ivosidenib<\/p>\n<\/td>\n
\n
Olutasidenib<\/p>\n<\/td>\n
\n
Olutasidenib<\/p>\n<\/td>\n
\n
Olutasidenib + AZA<\/p>\n<\/td>\n<\/tr>\n
\n
Number of patients<\/b><\/p>\n<\/td>\n
\n
125<\/p>\n<\/td>\n
\n
22<\/p>\n<\/td>\n
\n
147<\/p>\n<\/td>\n
\n
26<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n
\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n
Median age, years<\/b><\/p>\n<\/td>\n
\n
67<\/p>\n<\/td>\n
\n
72<\/p>\n<\/td>\n
\n
71<\/p>\n<\/td>\n
\n
67<\/p>\n<\/td>\n<\/tr>\n
\n
Efficacy<\/b><\/p>\n<\/td>\n<\/tr>\n
\n
\u2003CR, %<\/p>\n<\/td>\n
\n
21.6<\/p>\n<\/td>\n
\n
18<\/p>\n<\/td>\n
\n
32<\/p>\n<\/td>\n
\n
12<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Median time to CR, months<\/p>\n<\/td>\n
\n
2.8<\/p>\n<\/td>\n
\n
1.9<\/p>\n<\/td>\n
\n
1.9<\/p>\n<\/td>\n
\n
1.9<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003CR\/CRh, %<\/p>\n<\/td>\n
\n
30.4<\/p>\n<\/td>\n
\n
32<\/p>\n<\/td>\n
\n
35<\/p>\n<\/td>\n
\n
16<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003ORR, %<\/p>\n<\/td>\n
\n
41.6<\/p>\n<\/td>\n
\n
41<\/p>\n<\/td>\n
\n
48<\/p>\n<\/td>\n
\n
46<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Median duration of CR\/CRh, months<\/p>\n<\/td>\n
\n
8.2<\/p>\n<\/td>\n
\n
NA<\/p>\n<\/td>\n
\n
25.9<\/p>\n<\/td>\n
\n
NA<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Median DOR, months<\/p>\n<\/td>\n
\n
6.5<\/p>\n<\/td>\n
\n
NA<\/p>\n<\/td>\n
\n
11.7<\/p>\n<\/td>\n
\n
NA<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Median OS, months<\/p>\n<\/td>\n
\n
8.8<\/p>\n<\/td>\n
\n
8.7<\/p>\n<\/td>\n
\n
11.6<\/p>\n<\/td>\n
\n
12.1<\/p>\n<\/td>\n<\/tr>\n
\n
Safety: grade 3 or more AEs, %<\/b><\/p>\n<\/td>\n<\/tr>\n
\n
\u2003QT prolongation<\/p>\n<\/td>\n
\n
8.9<\/p>\n<\/td>\n
\n
0<\/p>\n<\/td>\n
\n
1*<\/span><\/span><\/p>\n<\/td>\n
\n
7^{\u2020<\/sup><\/p>\n<\/td>\n<\/tr>\n}
\n
\u2003DS<\/p>\n<\/td>\n
\n
5.4<\/p>\n<\/td>\n
\n
9<\/p>\n<\/td>\n
\n
8<\/p>\n<\/td>\n
\n
7<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Anaemia<\/p>\n<\/td>\n
\n
19<\/p>\n<\/td>\n
\n
22<\/p>\n<\/td>\n
\n
20<\/p>\n<\/td>\n
\n
20<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Thrombocytopaenia<\/p>\n<\/td>\n
\n
13.6<\/p>\n<\/td>\n
\n
28<\/p>\n<\/td>\n
\n
16<\/p>\n<\/td>\n
\n
41<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Febrile neutropaenia<\/p>\n<\/td>\n
\n
24.8<\/p>\n<\/td>\n
\n
22<\/p>\n<\/td>\n
\n
20<\/p>\n<\/td>\n
\n
28<\/p>\n<\/td>\n<\/tr>\n
\n
\u2003Hepatic enzyme increase<\/p>\n<\/td>\n
\n
NA<\/p>\n<\/td>\n
\n
16<\/p>\n<\/td>\n
\n
3<\/p>\n<\/td>\n
\n
11<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n
\n
\n
*<\/span>C<\/span>onsidered as unrelated to treatment.<\/em><\/p>\n<\/div>\n
\n
^{\u2020<\/sup>G<\/span>rade 2\u20133.<\/em><\/p>\n<\/div>\n}
\n
AE<\/span>\u00a0=\u00a0adverse event<\/span>; <\/span>AZA<\/span>\u00a0=\u00a05-azacytidine<\/span>; <\/span>CR<\/span>\u00a0=\u00a0complete response<\/span>; <\/span>CRh<\/span>\u00a0=\u00a0complete response with partial haematological recovery<\/span>; <\/span>DOR<\/span>\u00a0=\u00a0duration of response<\/span>; <\/span>DS<\/span>\u00a0=\u00a0differentiation syndrome<\/span>; <\/span>NA<\/span>\u00a0=\u00a0not available<\/span>; <\/span>ORR<\/span>\u00a0=\u00a0overall response rate<\/span>; <\/span>OS<\/span>\u00a0=\u00a0overall survival<\/span>.<\/span><\/em><\/p>\n<\/div>\n<\/div>\n<\/div>\n
A high-throughput screening led to the discovery of quinolinone derivatives as specific inhibitors of mIDH1.^{106<\/sup><\/span>\u00a0Structure-based design and optimization of candidate compounds generated olutasidenib (FT-2102), a brain-penetrant, potent, selective and orally bioavailable inhibitor of\u00a0IDH1<\/em>\u00a0R132 mutants. Olutasidenib efficiently inhibits D-2HG production in xenograft models, with no activity against wtIDH1. Olutasidenib is an allosteric inhibitor of mIDH1 and binds a hydrophobic pocket near the heterodimer interface and stabilizes the mutant enzyme in its open inactive conformation.^{107<\/sup><\/span>\u00a0Olutasidenib has a different structure and binding properties than ivosidenib, and an\u00a0in vitro<\/em>\u00a0study suggested that it could overcome the resistance to ivosidenib due to second-site mutations.^{108<\/sup><\/span><\/p>\n}}}
Efficacy of olutasidenib<\/h2>\n
The pivotal multicentre, open-label phase I\/II trial 2102-HEM-101 (Open-label study of FT-2102 with or without azacitidine or cytarabine in patients with AML or MDS with an\u00a0IDH1<\/em>\u00a0mutation<\/span>;\u00a0ClinicalTrials.gov identifier:\u00a0<\/span>NCT02719574) aimed to evaluate olutasidenib as a single agent or in combination with azacitidine in patients with AML and MDS with\u00a0IDH1<\/em>\u00a0mutations<\/em><\/span><\/span>.^{97<\/sup><\/span>\u00a0The FDA approved olutasidenib on 1 December 2022 for adult patients with R\/R AML with\u00a0IDH1<\/em>\u00a0mutations due to a high response rate, durability of the response and favourable safety profile.^{20<\/sup><\/span>\u00a0No dose-limiting toxicities were observed in the dose-escalation phase, and olutasidenib 150 mg twice daily in continuous 28-day cycles was identified as the recommended phase II dose.^{109<\/sup><\/span><\/p>\n}}}
Response and survival with olutasidenib as a single agent<\/h2>\n
The phase I study enrolled adult patients with AML and MDS who were R\/R or unfit for standard treatment (<\/em>Table 1<\/em><\/span>). The patients were allocated to receive olutasidenib as a single agent or in combination with azacitidine if they were eligible for hypomethylating agents. Between 2014 and 2016, 32 patients received olutasidenib as monotherapy, including 22 (69%) R\/R AML and 4 (15%) with treatment-naive AML. The\u00a0m<\/span>edian age was 72 years. Among patients with R\/R AML, CR, CR\/CRi and ORR were 18% (95%\u00a0confidence interval<\/span>\u00a0[CI], 5\u201340), 32% (95% CI, 14\u201355) and 41% (95% CI, 21\u201364), respectively. The median time to the first response was 1.9 months. The median OS was 8.7 months (95% CI, 2.5\u2013not estimable [NE]). The\u00a0e<\/span>stimated 12-month OS was 44% (95% CI, 23\u201364). Median progression-free survival (PFS) was 16.3 weeks (95% CI, 5.1\u201324.0). These results are similar to those reported for ivosidenib in a comparable population of patients with AML.^{99<\/sup><\/span>\u00a0Among treatment-naive patients, ORR was 25% (one of the four), median OS was 8.8 months (95% CI, 0.6\u201314.5) and the 12-month OS was 50% (95% CI, 6\u201385).^{109<\/sup><\/span><\/p>\n}}
A preplanned interim analysis in patients with mIDH1<\/em>\u00a0R\/R AML who received olutasidenib alone in the pivotal phase II cohort of the trial confirmed the encouraging results of the phase I study (Table 1<\/em><\/span>).^{98<\/sup><\/span>\u00a0Efficacy was evaluated in 147 patients who received the first dose of olutasidenib at least 6 months before data cut-off. CR, CR\/CRh (primary endpoint) and OR were achieved in 32% (95% CI, 24.5\u201340.2), 35% (95% CI, 27.0\u201343.0) and 48% (95% CI, 40.0\u201356.7), respectively. The\u00a0m<\/span>edian duration of response (DOR) was 11.7 months (95% CI, 6.9\u201325.9), the median duration of CR was 28.1 months (95% CI, 13.8\u2013NE) and the median duration of CR\/CRh was 25.9 months (95% CI, 13.5\u2013NE). The\u00a0m<\/span>edian OS was 11.6 months (95% CI, 8.9\u201315.5) and correlated to response: the median OS was not achieved in patients who reached CR\/CRh and was 4 months for non-responders. Responders had lower\u00a0IDH<\/em>\u00a0variant allele frequency (VAF) at diagnosis, fewer co-mutations, less\u00a0FLT3<\/em>\u00a0mutations and less receptor tyrosine kinase (RTK) pathway mutations. Of note, patients with\u00a0IDH1<\/em>\u00a0R132H mutation had a relatively lower CR\/CRh rate compared with other mutation subtypes and tended to have more co-mutations, particularly mutations in\u00a0NPM1<\/em>\u00a0and\u00a0RTK<\/em>\u00a0genes, including\u00a0FLT3<\/em>.<\/p>\n}
Response and survival with olutasidenib in combination with azacitidine<\/h2>\n
Among patients with R\/R AML treated in the combination therapy group of the phase I study, ORR was 46% (95% CI, 27\u201367). Twelve per cent (95% CI, 2\u201330) of patients achieved CR. The\u00a0m<\/span>edian time to the first response was 1.9 months, and the median DOR was 2.0 months (95% CI, 0.9\u20133.2). The\u00a0m<\/span>edian OS was 12.1 (95% CI, 4.2\u2013NE) months (Table 1<\/em><\/span>). The\u00a0e<\/span>stimated 12-month OS was 54% (95% CI, 32\u201371). The\u00a0m<\/span>edian PFS was 19.6 weeks (95% CI, 11.1\u201323.7). Among the 13 patients with treatment-naive AML treated in the combination arm, the ORR was 77%. The\u00a0m<\/span>edian DOR and median OS were not reached. The\u00a0e<\/span>stimated 12-month OS was 75% (95% CI, 41\u201391).^{109,110<\/sup><\/span><\/p>\n}
Haematological improvement<\/h2>\n
Red blood cell (RBC) and\/or platelet transfusion independence (TI) during any 56-day post-baseline period was achieved in patients treated with olutasidenib as a single agent as well as in patients treated with the olutasidenib\u2013azacitidine combination. Forty per cent and 34% of patients under olutasidenib alone achieved TI during the phase I and phase II parts of the trial, respectively. In the combination group of the phase I study, 33% of patients with AML achieved TI. TI was correlated to response, as 100% and 88% of patients achieving CR\/CRh in the phase II study reached platelet and RBC TI, respectively. Most patients with an abnormal absolute neutrophil count at baseline had improvement on treatment.^{98,109,110<\/sup><\/span><\/p>\n}
Molecular response<\/h2>\n
In the phase I study, a significant reduction in\u00a0IDH1<\/em>\u00a0VAF of <1% was observed in 40% of patients with AML who had a response. One patient in the olutasidenib group and one patient in the combination therapy group obtained molecular clearance by NGS.^{109<\/sup><\/span>\u00a0In the phase II study, molecular clearance was correlated to response with 28% of VAF clearance in patients with CR\/CRh, 8% of VAF clearance in other responders and 7% of VAF clearance in non-responders. After two cycles, the median D-2HG concentration was reduced by 82% in responders.^{98<\/sup><\/span><\/p>\n}}
Toxicity of olutasidenib<\/h2>\n
In the 2102-HEM-101 trial, olutasidenib had a favourable safety profile similar to that of ivosidenib (Table 1<\/em><\/span>).^{98,109,110<\/sup><\/span>\u00a0All patients reported at least one adverse event (AE) of any grade, irrespective of the relation to olutasidenib. In both phase I and II studies, the most frequent AEs of any grade (mostly grade 1\/2) were gastrointestinal disorders (nausea, constipation, diarrhoea and vomiting), pyrexia, fatigue, dyspnoea and hypokalaemia. Among grade 3\u20134 AEs, haematological AEs were the most frequent. Grade 3\u20134 thrombocytopaenia, febrile neutropaenia and anaemia occurred in around 20% of patients receiving olutasidenib as a single agent and neutropaenia in around 10% of them. Grade 3\u20134 thrombocytopaenia and febrile neutropaenia were more frequent in the combination therapy group (41 and 28%, respectively). Of note, other AEs were similar for olutasidenib given as monotherapy or in combination.<\/p>\n}
Around 75% of patients presented serious AEs, including disease progression, febrile neutropaenia, pneumonia and differentiation syndrome (DS). Thirteen per cent of patients in both arms of the phase I study and 14% of patients in the olutasidenib arm of the phase II study had DS of all grades. Grade 3\u20134 DS was reported in 9% of patients receiving olutasidenib as a single agent and in 7% of patients in the combination arm, mostly during cycle 1. Most of them were successfully managed with olutasidenib interruption or dose reduction, dexamethasone, hydroxycarbamide and diuretics. The rate of DS with olutasidenib is similar to that reported with ivosidenib.^{99<\/sup><\/span>\u00a0Grade 3\u20134 hepatic AEs of special interest occurred in around 15% treated with olutasidenib alone and in 11% of patients on combination treatment. The most frequent event was an increase in laboratory liver function parameters. None led to the criteria for Hy\u2019s law or liver failure. Fatal AEs were reported in 34% of patients treated in the olutasidenib arm of the phase I study, in 31% of patients treated in the olutasidenib arm of the phase II study and in 20% of patients in the phase I combination therapy. The most common fatal AEs were disease progression (in 9, 14 and 9% of patients, respectively) and infections. QT interval prolongation occurred in 7% of patients of the phase I cohort and 8% in the monotherapy arm of the phase II cohort. None of them was reported as serious, all were transient and no treatment interruption was required. Of note, these patients were frequently taking concomitant medications associated with QT prolongation. In conclusion, AEs were mostly expected and highly manageable with dose modification and standard-of-care measures. The toxicity profile of olutasidenib seems to be quite similar to that of ivosidenib.<\/p>\n}
Discussion<\/span><\/h1>\n
The discovery of\u00a0IDH<\/em>\u00a0mutations allowed the development of a new class of drugs, mIDH inhibitors. The\u00a0e<\/span>fficacy of these new molecules in preclinical studies and in clinical trials validated\u00a0mIDH<\/em>\u00a0targeting as an effective treatment strategy.<\/p>\n
The tolerance of mIDH inhibitors is excellent. Olutasidenib has a safety profile similar to that of ivosidenib (Table 1<\/em><\/span>). Their side effects are well characterized and easily manageable with dose modifications and standard-of-care measures, allowing their administration to patients unfit for standard therapies, even in the elderly.^{111<\/sup><\/span>\u00a0Ivosidenib as a single agent has proven its clinical efficacy in heavily pre-treated or unfit patients with AML with clinical benefits.^{99,101<\/sup><\/span>\u00a0Similar response rates are observed with olutasidenib in a similar population of patients treated in the 2102-HEM-101 trial (Table 1<\/em><\/span>). DOR with olutasidenib is promising.^{98,109<\/sup><\/span>\u00a0More interesting results are obtained with the combination of mIDH inhibitors with hypomethylating agents.^{112<\/sup><\/span>\u00a0In the phase III AGILE trial, a clear clinical benefit was observed in the ivosidenib arm with a significant survival improvement compared with the placebo arm.^{102<\/sup><\/span>\u00a0Results of the combination of olutasidenib and azacytidine in the phase I study of the 2102-HEM-101 trial are promising, especially in patients with ND AML,^{<\/sup>\u00a0and the data of the phase II part of the trial are eagerly awaited.^{109<\/sup><\/span><\/p>\n}}}}}}}
Moreover, the development of new molecules, such as the BCL2 inhibitor venetoclax, allows the administration of a triplet regimen, which appears well tolerated and could potentially overcome resistance to treatment.^{113<\/sup><\/span>\u00a0A phase I clinical trial showed the feasibility of the association of ivosidenib with intensive chemotherapy for ND patients with AML with encouraging clinical activity.^{114<\/sup><\/span>\u00a0A phase III randomized clinical trial is ongoing to evaluate the benefit of adding IDHm inhibitors to chemotherapy in frontline (<\/span>A study of ivosidenib or enasidenib in combination with induction therapy and consolidation therapy, followed by maintenance therapy in patients with newly diagnosed acute myeloid leukemia or myedysplastic syndrome EB2, with an IDH1 or IDH2 mutation, respectively, eligible for intensive chemotherapy [HOVON150AML]<\/span>, ClinicalTrials.gov identifier: NCT03839771). Of note, olutasidenib crossed the blood\u2013brain barrier and exerted clinical activity in a phase Ib\/II trial of R\/R mIDH1<\/em>\u00a0gliomas. It could, therefore, be of interest in patients with AML with central nervous system involvement.<\/p>\n}}
Conclusion<\/h1>\n
O<\/span>lutasidenib has encouraging clinical activity in the treatment of unfit patients with R\/R or AML allowing clinical improvement, with a safe toxicity profile. Only a direct comparison with ivosidenib could highlight the differences in the efficacy and safety of these drugs. However, DORs to olutasidenib seem particularly promising. The\u00a0e<\/span>fficacy data of olutasidenib in combination with azacytidine are awaited.<\/p>\n","protected":false},"excerpt":{"rendered":"
Key points Olutasidenib induces durable responses in patients with relapsed or refractory (R\/R) acute myeloid leukaemia (AML) with isocitrate dehydrogenase 1 (IDH1)\u00a0mutations in the phase I and II clinical trials. The\u00a0side effects of olutasidenib are well known and highly manageable. Olutasidenib represents a therapeutic advance for these patients with a poor prognosis. Olutasidenib received the […]<\/p>\n","protected":false},"author":142327,"featured_media":71442,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","rank_math_lock_modified_date":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-103887","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","vocabulary_1-leukaemia","journal-touchreviews-in-oncology-haematology"],"acf":{"wpcf-article_introduction":"","wpcf-article_abstract":"Management of patients with relapsed or refractory (R\/R) acute myeloid leukaemia (AML) is challenging, as their prognosis remains poor with conventional therapies, underlining the need for the development of new drugs. Isocitrate dehydrogenase (IDH) inhibitors are targeted therapies that have been developed over several years for the treatment of AML. This review will focus on olutasidenib, a selective, oral, small-molecule inhibitor of the mutant IDH1 enzyme, approved by the\u00a0US Food and Drug Administration<\/span>\u00a0(FDA) on 01 December 2022 for adult patients with R\/R AML with\u00a0IDH1<\/em>\u00a0mutation detected by an FDA-approved test. We will review the mechanisms of\u00a0IDH1<\/em>\u00a0mutations in AML, inhibition of mutations by olutasidenib and the clinical efficacy and safety of olutasidenib in R\/R AML.","wpcf-article_keywords":"Acute myeloid leukaemia<\/span>,\u00a0epigenetic<\/span>,\u00a02-hydroxyglutarate (2-HG)<\/span>,\u00a0isocitrate dehydrogenase 1 (IDH1), <\/span>olutasidenib, <\/span>targeted therapies<\/span>","wpcf-article_citation_override":"touchREVIEWS in Oncology & Haematology.<\/i> 2024;20(1):25\u201331","wpcf-compliance-with-ethics":"
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This article involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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Florence Pasquier has no financial or non-financial relationships or activities to declare in relation to this article. St\u00e9phane De Botton has received honoraria and research funding from Forma Therapeutics; has received honoraria and research funding from and is a consultant to Agios; has received honoraria from, is a consultant to and is on the speakers\u2019 bureau for Celgene; has received honoraria from and is a consult to Astellas, Daiichi Sankyo, Syros, AbbVie, Bayer and Janssen and has received honoraria from Seattle Genetics and is a consultant to Pierre Fabre, Novartis, Pfizer and Servier.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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Double-blind peer review.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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All named authors meet the criteria of the International Committee of Medical Journal Editors for authorship for this manuscript, take responsibility for the integrity of the work as a whole and have given final approval for the version to be published.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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Florence<\/span>\u00a0Pasquier<\/span><\/span>,\u00a0D\u00e9partement d\u2019H\u00e9matologie Clinique, Institut Gustave Roussy<\/span>,\u00a0114 rue Edouard Vaillant<\/span>,\u00a0948005 Villejuif Cedex, <\/span>France; <\/span><\/span>florence.pasquier@gustaveroussy.fr<\/span><\/p>\r\n\r\n
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No funding was received in the publication of this article.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>","wpcf-open_access":"
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This article is freely accessible at touchONCOLOGY.com \u00a9 Touch Medical Media 2024.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
<\/div>","wpcf-article_pdf":"https:\/\/touchoncology.com\/wp-content\/uploads\/sites\/2\/2024\/03\/7.-touchONC_20.1_Pasquier_25-31.pdf","wpcf-article_pdf-gated":true,"wpcf-article_doi":"https:\/\/doi.org\/10.17925\/OHR.2024.20.1.6","wpcf-old_nid":"","wpcf-article_image":"","wpcf-editor_choice":false,"wpcf-old_author_ids":"","wpcf-article_references":"
1.<\/span>\u00a0D\u00f6hner<\/span>\u00a0H<\/span><\/span>,\u00a0Weisdorf<\/span>\u00a0DJ<\/span><\/span>,\u00a0Bloomfield<\/span>\u00a0CD<\/span><\/span>.\u00a0Acute myeloid leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02015<\/span>;373<\/span>:1136<\/span>\u201352. <\/span>DOI<\/span>:\u00a010.1056\/NEJMra1406184<\/span>.<\/p>\r\n
2.<\/span>\u00a0Burnett<\/span>\u00a0AK<\/span><\/span>,\u00a0Goldstone<\/span>\u00a0A<\/span><\/span>,\u00a0Hills<\/span>\u00a0RK<\/span><\/span>,\u00a0et al<\/span>.\u00a0Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02013<\/span>;31<\/span>:1293<\/span>\u2013301<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2011.40.5977<\/span>.<\/p>\r\n
3.<\/span>\u00a0Shallis<\/span>\u00a0RM<\/span><\/span>,\u00a0Wang<\/span>\u00a0R<\/span><\/span>,\u00a0Davidoff<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges<\/span>.\u00a0Blood Rev<\/em><\/span>.\u00a02019<\/span>;36<\/span>:70<\/span>\u201387<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.blre.2019.04.005<\/span>.<\/p>\r\n
4.<\/span>\u00a0Derolf<\/span>\u00a0AR<\/span><\/span>,\u00a0Kristinsson<\/span>\u00a0SY<\/span><\/span>,\u00a0Andersson<\/span>\u00a0TM-L<\/span><\/span>,\u00a0et al<\/span>.\u00a0Improved patient survival for acute myeloid leukemia:\u00a0A<\/span>\u00a0population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005<\/span>.\u00a0Blood<\/em><\/span>.\u00a02009<\/span>;113<\/span>:3666<\/span>\u201372. <\/span>DOI<\/span>:\u00a010.1182\/blood-2008-09-179341<\/span>.<\/p>\r\n
5.<\/span>\u00a0\u00d8stg\u00e5rd<\/span>\u00a0LSG<\/span><\/span>,\u00a0N\u00f8rgaard<\/span>\u00a0M<\/span><\/span>,\u00a0N\u00f8rgaard<\/span>\u00a0JM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Data quality in the Danish National Acute Leukemia Registry: A hematological data resource<\/span>.\u00a0Clin Epidemiol<\/em><\/span>.\u00a02013<\/span>;335<\/span>:335<\/span>.\u00a0DOI<\/span>:\u00a010.2147\/CLEP.S48411<\/span>.<\/p>\r\n
6.<\/span>\u00a0National Cancer Institute Surveillance, Epidemiology, and End Results Program<\/span>.\u00a0Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia (AML)<\/span>.\u00a02023<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/seer.cancer.gov\/statfacts\/html\/amyl.html<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
7.<\/span>\u00a0Mardis<\/span>\u00a0ER<\/span><\/span>,\u00a0Ding<\/span>\u00a0L<\/span><\/span>,\u00a0Dooling<\/span>\u00a0DJ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Recurring mutations found by sequencing an acute myeloid leukemia genome<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02009<\/span>;361<\/span>:1058<\/span>\u201366<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa0903840<\/span>.<\/p>\r\n
8.<\/span>\u00a0Ley<\/span>\u00a0TJ<\/span><\/span>,\u00a0Miller<\/span>\u00a0C<\/span><\/span>,\u00a0Ding<\/span>\u00a0L<\/span><\/span>,\u00a0et al<\/span>.\u00a0Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02013<\/span>;368<\/span>:2059<\/span>\u201374<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1301689<\/span>.<\/p>\r\n
9.<\/span>\u00a0Kosmider<\/span>\u00a0O<\/span><\/span>,\u00a0Gelsi-Boyer<\/span>\u00a0V<\/span><\/span>,\u00a0Slama<\/span>\u00a0L<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS\/myeloproliferative\u00a0n<\/span>eoplasms<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02010<\/span>;24<\/span>:1094<\/span>\u20136. <\/span>DOI<\/span>:\u00a010.1038\/leu.2010.52<\/span>.<\/p>\r\n
10.<\/span>\u00a0Thol<\/span>\u00a0F<\/span><\/span>,\u00a0Weissinger<\/span>\u00a0EM<\/span><\/span>,\u00a0Krauter<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis<\/span>.\u00a0Haematologica<\/em><\/span>.\u00a02010<\/span>;95<\/span>:1668<\/span>\u201374<\/span>.\u00a0DOI<\/span>:\u00a010.3324\/haematol.2010.025494<\/span>.<\/p>\r\n
11.<\/span>\u00a0Tefferi<\/span>\u00a0A<\/span><\/span>,\u00a0Lasho<\/span>\u00a0TL<\/span><\/span>,\u00a0Abdel-Wahab<\/span>\u00a0O<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02010<\/span>;24<\/span>:1302<\/span>\u20139. <\/span>DOI<\/span>:\u00a010.1038\/leu.2010.113<\/span>.<\/p>\r\n
12.<\/span>\u00a0Parsons<\/span>\u00a0DW<\/span><\/span>,\u00a0Jones<\/span>\u00a0S<\/span><\/span>,\u00a0Zhang<\/span>\u00a0X<\/span><\/span>,\u00a0et al<\/span>.\u00a0An integrated genomic analysis of human glioblastoma multiforme. <\/span>Science<\/em><\/span>.\u00a02008<\/span>;321<\/span>:1807<\/span>\u201312<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1164382<\/span>.<\/p>\r\n
13.<\/span>\u00a0Yan<\/span>\u00a0H<\/span><\/span>,\u00a0Parsons<\/span>\u00a0DW<\/span><\/span>,\u00a0Jin<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 and IDH2 mutations in gliomas<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02009<\/span>;360<\/span>:765<\/span>\u201373. <\/span>DOI<\/span>:\u00a010.1056\/NEJMoa0808710<\/span>.<\/p>\r\n
14.<\/span>\u00a0Wang<\/span>\u00a0P<\/span><\/span>,\u00a0Dong<\/span>\u00a0Q<\/span><\/span>,\u00a0Zhang<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas<\/span>.\u00a0Oncogene<\/em><\/span>.\u00a02013<\/span>;32<\/span>:3091<\/span>\u2013100. <\/span>DOI<\/span>:\u00a010.1038\/onc.2012.315<\/span>.<\/p>\r\n
15.<\/span>\u00a0Genovese<\/span>\u00a0G<\/span><\/span>,\u00a0K\u00e4hler<\/span>\u00a0AK<\/span><\/span>,\u00a0Handsaker<\/span>\u00a0RE<\/span><\/span>,\u00a0et al<\/span>.\u00a0Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02014<\/span>;371<\/span>:2477<\/span>\u201387<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1409405<\/span>.<\/p>\r\n
16.<\/span>\u00a0Corces-Zimmerman<\/span>\u00a0MR<\/span><\/span>,\u00a0Hong<\/span>\u00a0W-J<\/span><\/span>,\u00a0Weissman<\/span>\u00a0IL<\/span><\/span>,\u00a0et al<\/span>.\u00a0Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission<\/span>.\u00a0Proc Natl Acad Sci U S A<\/em><\/span>.\u00a02014<\/span>;111<\/span>:2548<\/span>\u201353. <\/span>DOI<\/span>:\u00a010.1073\/pnas.1324297111<\/span>.<\/p>\r\n
17.<\/span>\u00a0US Food and Drug Administration<\/span>.\u00a0FDA approves first targeted treatment for patients with relapsed or refractory acute myeloid leukemia who have a certain genetic mutation [Press Release]<\/span>.\u00a02018<\/span>.\u00a0Available at<\/span>:\u00a0www.fda.gov\/news-events\/press-announcements\/fda-approves-first-targeted-treatment-patients-relapsed-or-refractory-acute-myeloid-leukemia-who<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
18.<\/span>\u00a0US Food and Drug Administration<\/span>.\u00a0FDA approves ivosidenib as first-line treatment for AML with IDH1 mutation FDA approves ivosidenib as first-line treatment for AML with IDH1 mutation [Press Release]<\/span>.\u00a02022<\/span>.\u00a0Available at<\/span>:\u00a0 www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ivosidenib-combination-azacitidine-newly-diagnosed-acute-myeloid-leukemia<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
19.<\/span>\u00a0US Food and Drug Administration<\/span>.\u00a0FDA approves ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia [Press Release]<\/span>.\u00a02022<\/span>.\u00a0Available at<\/span>:\u00a0 www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ivosidenib-combination-azacitidine-newly-diagnosed-acute-myeloid-leukemia<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
20.<\/span>\u00a0US Food and Drug Administration<\/span>.\u00a0FDA approves olutasidenib for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation [Press Release]<\/span>.\u00a02022<\/span>.\u00a0Available at<\/span>:\u00a0 www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-olutasidenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-idh1-mutation<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
21.<\/span>\u00a0Geisbrecht<\/span>\u00a0BV<\/span><\/span>,\u00a0Gould<\/span>\u00a0SJ<\/span><\/span>.\u00a0The human PICD gene encodes a cytoplasmic and peroxisomal NADP+-dependent isocitrate dehydrogenase<\/span>.\u00a0J Biol Chem<\/em><\/span>.\u00a01999<\/span>;274<\/span>:30527<\/span>\u201333<\/span>.\u00a0DOI<\/span>:\u00a010.1074\/jbc.274.43.30527<\/span>.<\/p>\r\n
22.<\/span>\u00a0Lee<\/span>\u00a0SM<\/span><\/span>,\u00a0Koh<\/span>\u00a0H-J<\/span><\/span>,\u00a0Park<\/span>\u00a0D-C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cytosolic NADP + -dependent isocitrate dehydrogenase status modulates oxidative damage to cells<\/span>.\u00a0Free Radic Biol Med<\/em><\/span>.\u00a02002<\/span>;32<\/span>:1185<\/span>\u201396<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/s0891-5849(02)00815-8<\/span>.<\/p>\r\n
23.<\/span>\u00a0Yen<\/span>\u00a0KE<\/span><\/span>,\u00a0Bittinger<\/span>\u00a0MA<\/span><\/span>,\u00a0Su<\/span>\u00a0SM<\/span><\/span>,\u00a0Fantin<\/span>\u00a0VR<\/span><\/span>.\u00a0Cancer-associated IDH mutations: Biomarker and therapeutic opportunities<\/span>.\u00a0Oncogene<\/em><\/span>.\u00a02010<\/span>;29<\/span>:6409<\/span>\u201317<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/onc.2010.444<\/span>.<\/p>\r\n
24.<\/span>\u00a0Cairns<\/span>\u00a0RA<\/span><\/span>,\u00a0Mak<\/span>\u00a0TW<\/span><\/span>.\u00a0Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and clinical opportunities<\/span>.\u00a0Cancer Discov<\/em><\/span>.\u00a02013<\/span>;3<\/span>:730<\/span>\u201341<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/2159-8290.CD-13-0083<\/span>.<\/p>\r\n
25.<\/span>\u00a0Tsukada<\/span>\u00a0Y<\/span><\/span>,\u00a0Fang<\/span>\u00a0J<\/span><\/span>,\u00a0Erdjument-Bromage<\/span>\u00a0H<\/span><\/span>,\u00a0et al<\/span>.\u00a0Histone demethylation by a family of JmjC domain-containing proteins<\/span>.\u00a0Nature<\/em><\/span>.\u00a02006<\/span>;439<\/span>:811<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature04433<\/span>.<\/p>\r\n
26.<\/span>\u00a0Loenarz<\/span>\u00a0C<\/span><\/span>,\u00a0Schofield<\/span>\u00a0CJ<\/span><\/span>.\u00a0Expanding chemical biology of 2-oxoglutarate oxygenases<\/span>.\u00a0Nat Chem Biol<\/em><\/span>.\u00a02008<\/span>;4<\/span>:152<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nchembio0308-152<\/span>.<\/p>\r\n
27.<\/span>\u00a0Mullen<\/span>\u00a0AR<\/span><\/span>,\u00a0Wheaton<\/span>\u00a0WW<\/span><\/span>,\u00a0Jin<\/span>\u00a0ES<\/span><\/span>,\u00a0et al<\/span>.\u00a0Reductive carboxylation supports growth in tumour cells with defective mitochondria<\/span>.\u00a0Nature<\/em><\/span>.\u00a02012<\/span>;481<\/span>:385<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature10642<\/span>.<\/p>\r\n
28.<\/span>\u00a0Mullen<\/span>\u00a0AR<\/span><\/span>,\u00a0Hu<\/span>\u00a0Z<\/span><\/span>,\u00a0Shi<\/span>\u00a0X<\/span><\/span>,\u00a0et al<\/span>.\u00a0Oxidation of alpha-k<\/span>etoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects<\/span>.\u00a0Cell Rep<\/em><\/span>.\u00a02014<\/span>;7<\/span>:1679<\/span>\u201390<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.celrep.2014.04.037<\/span>.<\/p>\r\n
29.<\/span>\u00a0Jiang<\/span>\u00a0L<\/span><\/span>,\u00a0Shestov<\/span>\u00a0AA<\/span><\/span>,\u00a0Swain<\/span>\u00a0P<\/span><\/span>,\u00a0et al<\/span>.\u00a0Reductive carboxylation supports redox homeostasis during anchorage-independent growth<\/span>.\u00a0Nature<\/em><\/span>.\u00a02016<\/span>;532<\/span>:255<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature17393<\/span>.<\/p>\r\n
30.<\/span>\u00a0Hiller<\/span>\u00a0K<\/span><\/span>,\u00a0Metallo<\/span>\u00a0CM<\/span><\/span>.\u00a0Profiling metabolic networks to study cancer metabolism<\/span>.\u00a0Curr Opin Biotechnol<\/em><\/span>.\u00a02013<\/span>;24<\/span>:60<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.copbio.2012.11.001<\/span>.<\/p>\r\n
31.<\/span>\u00a0Icard<\/span>\u00a0P<\/span><\/span>,\u00a0Poulain<\/span>\u00a0L<\/span><\/span>,\u00a0Lincet<\/span>\u00a0H<\/span><\/span>.\u00a0Understanding the central role of citrate in the metabolism of cancer cells<\/span>.\u00a0Biochim Biophys Acta<\/em><\/span>.\u00a02012<\/span>;1825<\/span>:111<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.bbcan.2011.10.007<\/span>.<\/p>\r\n
32.<\/span>\u00a0Icard<\/span>\u00a0P<\/span><\/span>,\u00a0Coquerel<\/span>\u00a0A<\/span><\/span>,\u00a0Wu<\/span>\u00a0Z<\/span><\/span>,\u00a0et al<\/span>.\u00a0Understanding the central role of citrate in the metabolism of cancer cells and tumors: An update<\/span>.\u00a0Int J Mol Sci<\/em><\/span>.\u00a02021<\/span>;22<\/span>:12<\/span>.\u00a0DOI<\/span>:\u00a010.3390\/ijms22126587<\/span>.<\/p>\r\n
33.<\/span>\u00a0Zhao<\/span>\u00a0S<\/span><\/span>,\u00a0Lin<\/span>\u00a0Y<\/span><\/span>,\u00a0Xu<\/span>\u00a0W<\/span><\/span>,\u00a0et al<\/span>.\u00a0Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1\u0391<\/span>.\u00a0Science<\/em><\/span>.\u00a02009<\/span>;324<\/span>:261<\/span>\u20135<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1170944<\/span>.<\/p>\r\n
34.<\/span>\u00a0Dang<\/span>\u00a0L<\/span><\/span>,\u00a0White<\/span>\u00a0DW<\/span><\/span>,\u00a0Gross<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. <\/span>Nature. <\/em><\/span>2009<\/span>;462<\/span>:739<\/span>\u201344. <\/span>DOI<\/span>:\u00a010.1038\/nature08617<\/span>.<\/p>\r\n
35.<\/span>\u00a0Gross<\/span>\u00a0S<\/span><\/span>,\u00a0Cairns<\/span>\u00a0RA<\/span><\/span>,\u00a0Minden<\/span>\u00a0MD<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations<\/span>.\u00a0J Exp Med<\/em><\/span>.\u00a02010<\/span>;207<\/span>:339<\/span>\u201344. <\/span>DOI<\/span>:\u00a010.1084\/jem.20092506<\/span>.<\/p>\r\n
36.<\/span>\u00a0Ward<\/span>\u00a0PS<\/span><\/span>,\u00a0Patel<\/span>\u00a0J<\/span><\/span>,\u00a0Wise<\/span>\u00a0DR<\/span><\/span>,\u00a0et al<\/span>.\u00a0The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting \u0391-Ketoglutarate to 2-hydroxyglutarate<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02010<\/span>;17<\/span>:225<\/span>\u201334<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccr.2010.01.020<\/span>.<\/p>\r\n
37.<\/span>\u00a0Losman<\/span>\u00a0J-A<\/span><\/span>,\u00a0Looper<\/span>\u00a0RE<\/span><\/span>,\u00a0Koivunen<\/span>\u00a0P<\/span><\/span>,\u00a0et al<\/span>.\u00a0(R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible<\/span>.\u00a0Science<\/em><\/span>.\u00a02013<\/span>;339<\/span>:1621<\/span>\u20135<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1231677<\/span>.<\/p>\r\n
38.<\/span>\u00a0Xu<\/span>\u00a0W<\/span><\/span>,\u00a0Yang<\/span>\u00a0H<\/span><\/span>,\u00a0Liu<\/span>\u00a0Y<\/span><\/span>,\u00a0et al<\/span>.\u00a0Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of \u0391-ketoglutarate-dependent dioxygenases<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02011<\/span>;19<\/span>:17<\/span>\u201330<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccr.2010.12.014<\/span>.<\/p>\r\n
39.<\/span>\u00a0Figueroa<\/span>\u00a0ME<\/span><\/span>,\u00a0Abdel-Wahab<\/span>\u00a0O<\/span><\/span>,\u00a0Lu<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02010<\/span>;18<\/span>:553<\/span>\u201367. <\/span>DOI<\/span>:\u00a010.1016\/j.ccr.2010.11.015<\/span>.<\/p>\r\n
40.<\/span>\u00a0Ito<\/span>\u00a0S<\/span><\/span>,\u00a0Shen<\/span>\u00a0L<\/span><\/span>,\u00a0Dai<\/span>\u00a0Q<\/span><\/span>,\u00a0et al<\/span>.\u00a0TET proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine<\/span>.\u00a0Science<\/em><\/span>.\u00a02011<\/span>;333<\/span>:1300<\/span>\u20133<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1210597<\/span>.<\/p>\r\n
41.<\/span>\u00a0Ko<\/span>\u00a0M<\/span><\/span>,\u00a0Huang<\/span>\u00a0Y<\/span><\/span>,\u00a0Jankowska<\/span>\u00a0AM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2<\/span>.\u00a0Nature<\/em><\/span>.\u00a02010<\/span>;468<\/span>:839<\/span>\u201343<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature09586<\/span>.<\/p>\r\n
42.<\/span>\u00a0Noushmehr<\/span>\u00a0H<\/span><\/span>,\u00a0Weisenberger<\/span>\u00a0DJ<\/span><\/span>,\u00a0Diefes<\/span>\u00a0K<\/span><\/span>,\u00a0et al<\/span>.\u00a0Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02010<\/span>;17<\/span>:510<\/span>\u201322<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccr.2010.03.017<\/span>.<\/p>\r\n
43.<\/span>\u00a0Turcan<\/span>\u00a0S<\/span><\/span>,\u00a0Rohle<\/span>\u00a0D<\/span><\/span>,\u00a0Goenka<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype<\/span>.\u00a0Nature<\/em><\/span>.\u00a02012<\/span>;483<\/span>:479<\/span>\u201383<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature10866<\/span>.<\/p>\r\n
44.<\/span>\u00a0Akalin<\/span>\u00a0A<\/span><\/span>,\u00a0Garrett-Bakelman<\/span>\u00a0FE<\/span><\/span>,\u00a0Kormaksson<\/span>\u00a0M<\/span><\/span>,\u00a0et al<\/span>.\u00a0Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia<\/span>.\u00a0PLoS Genet. <\/em><\/span>2012<\/span>;8<\/span>:e1002781. <\/span>DOI<\/span>:\u00a010.1371\/journal.pgen.1002781<\/span>.<\/p>\r\n
45.<\/span>\u00a0Ceccarelli<\/span>\u00a0M<\/span><\/span>,\u00a0Barthel<\/span>\u00a0FP<\/span><\/span>,\u00a0Malta<\/span>\u00a0TM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma<\/span>.\u00a0Cell<\/em><\/span>.\u00a02016<\/span>;164<\/span>:550<\/span>\u201363<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.cell.2015.12.028<\/span>.<\/p>\r\n
46.<\/span>\u00a0Glass<\/span>\u00a0JL<\/span><\/span>,\u00a0Hassane<\/span>\u00a0D<\/span><\/span>,\u00a0Wouters<\/span>\u00a0BJ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Epigenetic identity in AML depends on disruption of nonpromoter regulatory elements and is affected by antagonistic effects of mutations in epigenetic modifiers<\/span>.\u00a0Cancer Discov<\/em><\/span>.\u00a02017<\/span>;7<\/span>:868<\/span>\u201383<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/2159-8290.CD-16-1032<\/span>.<\/p>\r\n
47.<\/span>\u00a0Turcan<\/span>\u00a0S<\/span><\/span>,\u00a0Makarov<\/span>\u00a0V<\/span><\/span>,\u00a0Taranda<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence<\/span>.\u00a0Nat Genet<\/em><\/span>.\u00a02018<\/span>;50<\/span>:62<\/span>\u201372<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41588-017-0001-z<\/span>.<\/p>\r\n
48.<\/span>\u00a0Ehrlich<\/span>\u00a0M<\/span><\/span>.\u00a0DNA hypermethylation in disease: mechanisms and clinical relevance<\/span>.\u00a0Epigenetics<\/em><\/span>.\u00a02019<\/span>;14<\/span>:1141<\/span>\u201363<\/span>.\u00a0DOI<\/span>:\u00a010.1080\/15592294.2019.1638701<\/span>.<\/p>\r\n
49.<\/span>\u00a0Rampal<\/span>\u00a0R<\/span><\/span>,\u00a0Alkalin<\/span>\u00a0A<\/span><\/span>,\u00a0Madzo<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia<\/span>.\u00a0Cell Rep<\/em><\/span>.\u00a02014<\/span>;9<\/span>:1841<\/span>\u201355<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.celrep.2014.11.004<\/span>.<\/p>\r\n
50.<\/span>\u00a0Wang<\/span>\u00a0Y<\/span><\/span>,\u00a0Xiao<\/span>\u00a0M<\/span><\/span>,\u00a0Chen<\/span>\u00a0X<\/span><\/span>,\u00a0et al<\/span>.\u00a0WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation<\/span>.\u00a0Mol Cell<\/em><\/span>.\u00a02015<\/span>;57<\/span>:662<\/span>\u201373<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.molcel.2014.12.023<\/span>.<\/p>\r\n
51.<\/span>\u00a0Lu<\/span>\u00a0C<\/span><\/span>,\u00a0Ward<\/span>\u00a0PS<\/span><\/span>,\u00a0Kapoor<\/span>\u00a0GS<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH mutation impairs histone demethylation and results in a block to cell differentiation<\/span>.\u00a0Nature<\/em><\/span>.\u00a02012<\/span>;483<\/span>:474<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature10860<\/span>.<\/p>\r\n
52.<\/span>\u00a0Su<\/span>\u00a0R<\/span><\/span>,\u00a0Dong<\/span>\u00a0L<\/span><\/span>,\u00a0Li<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0R-2HG exhibits anti-tumor activity by targeting FTO\/M6A\/MYC\/CEBPA signaling. <\/span>Cell. <\/em><\/span>2018<\/span>;172<\/span>:90<\/span>\u2013105. <\/span>DOI<\/span>:\u00a010.1016\/j.cell.2017.11.031<\/span>.<\/p>\r\n
53.<\/span>\u00a0Chen<\/span>\u00a0C<\/span><\/span>,\u00a0Liu<\/span>\u00a0Y<\/span><\/span>,\u00a0Lu<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition<\/span>.\u00a0Genes Dev<\/em><\/span>.\u00a02013<\/span>;27<\/span>:1974<\/span>\u201385<\/span>.\u00a0DOI<\/span>:\u00a010.1101\/gad.226613.113<\/span>.<\/p>\r\n
54.<\/span>\u00a0Chaturvedi<\/span>\u00a0A<\/span><\/span>,\u00a0Araujo Cruz<\/span>\u00a0MM<\/span><\/span>,\u00a0Jyotsana<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML<\/span>.\u00a0Blood<\/em><\/span>.\u00a02013<\/span>;122<\/span>:2877<\/span>\u201387<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2013-03-491571<\/span>.<\/p>\r\n
55.<\/span>\u00a0Kats<\/span>\u00a0LM<\/span><\/span>,\u00a0Reschke<\/span>\u00a0M<\/span><\/span>,\u00a0Taulli<\/span>\u00a0R<\/span><\/span>,\u00a0et al<\/span>.\u00a0Proto-oncogenic role of mutant IDH2 in leukemia initiation and maintenance. <\/span>Cell Stem Cell<\/em><\/span>.\u00a02014<\/span>;14<\/span>:329<\/span>\u201341<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.stem.2013.12.016<\/span>.<\/p>\r\n
56.<\/span>\u00a0Shih<\/span>\u00a0AH<\/span><\/span>,\u00a0Meydan<\/span>\u00a0C<\/span><\/span>,\u00a0Shank<\/span>\u00a0K<\/span><\/span>,\u00a0et al<\/span>.\u00a0Combination targeted therapy to disrupt aberrant oncogenic signaling and reverse epigenetic dysfunction in IDH2- and TET2-mutant acute myeloid leukemia<\/span>.\u00a0Cancer Discov<\/em><\/span>.\u00a02017<\/span>;7<\/span>:494<\/span>\u2013505<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/2159-8290.CD-16-1049<\/span>.<\/p>\r\n
57.<\/span>\u00a0Chowdhury<\/span>\u00a0R<\/span><\/span>,\u00a0Yeoh<\/span>\u00a0KK<\/span><\/span>,\u00a0Tian<\/span>\u00a0Y-M<\/span><\/span>,\u00a0et al<\/span>.\u00a0The oncometabolite 2\u2010hydroxyglutarate inhibits histone lysine demethylases<\/span>.\u00a0EMBO Rep<\/em><\/span>.\u00a02011<\/span>;12<\/span>:463<\/span>\u20139<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/embor.2011.43<\/span>.<\/p>\r\n
58.<\/span>\u00a0Sulkowski<\/span>\u00a0PL<\/span><\/span>,\u00a0Corso<\/span>\u00a0CD<\/span><\/span>,\u00a0Robinson<\/span>\u00a0ND<\/span><\/span>,\u00a0et al<\/span>.\u00a02-hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity<\/span>.\u00a0Sci Transl Med. <\/em><\/span>2017<\/span>;9<\/span>:375. <\/span>DOI<\/span>:\u00a010.1126\/scitranslmed.aal2463<\/span>.<\/p>\r\n
59.<\/span>\u00a0Inoue<\/span>\u00a0S<\/span><\/span>,\u00a0Li<\/span>\u00a0WY<\/span><\/span>,\u00a0Tseng<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutant IDH1 downregulates ATM and alters DNA repair and sensitivity to DNA damage independent of TET2<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02016<\/span>;30<\/span>:337<\/span>\u201348<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccell.2016.05.018<\/span>.<\/p>\r\n
60.<\/span>\u00a0Wang<\/span>\u00a0P<\/span><\/span>,\u00a0Wu<\/span>\u00a0J<\/span><\/span>,\u00a0Ma<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Oncometabolite D-2-hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents<\/span>.\u00a0Cell Rep<\/em><\/span>.\u00a02015<\/span>;13<\/span>:2353<\/span>\u201361<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.celrep.2015.11.029<\/span>.<\/p>\r\n
61.<\/span>\u00a0Li<\/span>\u00a0Z<\/span><\/span>,\u00a0Weng<\/span>\u00a0H<\/span><\/span>,\u00a0Su<\/span>\u00a0R<\/span><\/span>,\u00a0et al<\/span>.\u00a0FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02017<\/span>;31<\/span>:127<\/span>\u201341<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccell.2016.11.017<\/span>.<\/p>\r\n
62.<\/span>\u00a0Elkashef<\/span>\u00a0SM<\/span><\/span>,\u00a0Lin<\/span>\u00a0A-P<\/span><\/span>,\u00a0Myers<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH\u00a0m<\/span>utation, competitive inhibition of FTO, and RNA methylation<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02017<\/span>;31<\/span>:619<\/span>\u201320<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccell.2017.04.001<\/span>.<\/p>\r\n
63.<\/span>\u00a0Shi<\/span>\u00a0J<\/span><\/span>,\u00a0Sun<\/span>\u00a0B<\/span><\/span>,\u00a0Shi<\/span>\u00a0W<\/span><\/span>,\u00a0et al<\/span>.\u00a0Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation<\/span>.\u00a0Tumor Biol<\/em><\/span>.\u00a02015<\/span>;36<\/span>:655<\/span>\u201362<\/span>.\u00a0DOI<\/span>:\u00a010.1007\/s13277-014-2644-z<\/span>.<\/p>\r\n
64.<\/span>\u00a0Biedermann<\/span>\u00a0J<\/span><\/span>,\u00a0Preussler<\/span>\u00a0M<\/span><\/span>,\u00a0Conde<\/span>\u00a0M<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutant IDH1 differently affects redox state and metabolism in glial cells of normal and tumor origin<\/span>.\u00a0Cancers<\/em><\/span>.\u00a02019<\/span>;11<\/span>:2028<\/span>.\u00a0DOI<\/span>:\u00a010.3390\/cancers11122028<\/span>.<\/p>\r\n
65.<\/span>\u00a0Liu<\/span>\u00a0Y<\/span><\/span>,\u00a0Lu<\/span>\u00a0Y<\/span><\/span>,\u00a0Celiku<\/span>\u00a0O<\/span><\/span>,\u00a0et al<\/span>.\u00a0Targeting IDH1-mutated malignancies with NRF2 blockade<\/span>.\u00a0J Natl Cancer Inst. <\/em><\/span>2019<\/span>;111<\/span>:1033<\/span>\u201341. <\/span>DOI<\/span>:\u00a010.1093\/jnci\/djy230<\/span>.<\/p>\r\n
66.<\/span>\u00a0Raffel<\/span>\u00a0S<\/span><\/span>,\u00a0Falcone<\/span>\u00a0M<\/span><\/span>,\u00a0Kneisel<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0BCAT1 restricts \u0391KG levels in AML stem cells leading to IDHmut-like DNA hypermethylation<\/span>.\u00a0Nature<\/em><\/span>.\u00a02017<\/span>;551<\/span>:384<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature24294<\/span>.<\/p>\r\n
67.<\/span>\u00a0McBrayer<\/span>\u00a0SK<\/span><\/span>,\u00a0Mayers<\/span>\u00a0JR<\/span><\/span>,\u00a0DiNatale<\/span>\u00a0GJ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Transaminase inhibition by 2-hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma<\/span>.\u00a0Cell<\/em><\/span>.\u00a02018<\/span>;175<\/span>:101<\/span>\u2013116<\/span>..\u00a0DOI<\/span>:\u00a010.1016\/j.cell.2018.08.038<\/span>.<\/p>\r\n
68.<\/span>\u00a0Grassian<\/span>\u00a0AR<\/span><\/span>,\u00a0Parker<\/span>\u00a0SJ<\/span><\/span>,\u00a0Davidson<\/span>\u00a0SM<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism<\/span>.\u00a0Cancer Res<\/em><\/span>.\u00a02014<\/span>;74<\/span>:3317<\/span>\u201331<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/0008-5472.CAN-14-0772-T<\/span>.<\/p>\r\n
69.<\/span>\u00a0Hvinden<\/span>\u00a0IC<\/span><\/span>,\u00a0Cadoux-Hudson<\/span>\u00a0T<\/span><\/span>,\u00a0Schofield<\/span>\u00a0CJ<\/span><\/span>,\u00a0McCullagh<\/span>\u00a0JSO<\/span><\/span>.\u00a0Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations<\/span>.\u00a0Cell Rep Med<\/em><\/span>.\u00a02021<\/span>;2<\/span>:100469<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.xcrm.2021.100469<\/span>.<\/p>\r\n
70.<\/span>\u00a0Chan<\/span>\u00a0SM<\/span><\/span>,\u00a0Thomas<\/span>\u00a0D<\/span><\/span>,\u00a0Corces-Zimmerman<\/span>\u00a0MR<\/span><\/span>,\u00a0et al<\/span>.\u00a0Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia<\/span>.\u00a0Nat Med<\/em><\/span>.\u00a02015<\/span>;21<\/span>:178<\/span>\u201384<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nm.3788<\/span>.<\/p>\r\n
71.<\/span>\u00a0Karpel-Massler<\/span>\u00a0G<\/span><\/span>,\u00a0Ishida<\/span>\u00a0CT<\/span><\/span>,\u00a0Bianchetti<\/span>\u00a0E<\/span><\/span>,\u00a0et al<\/span>.\u00a0Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL<\/span>.\u00a0Nat Commun<\/em><\/span>.\u00a02017<\/span>;8<\/span>:1067<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41467-017-00984-9<\/span>.<\/p>\r\n
72.<\/span>\u00a0Carbonneau<\/span>\u00a0M<\/span><\/span>,\u00a0M. Gagn\u00e9<\/span>\u00a0L<\/span><\/span>,\u00a0Lalonde<\/span>\u00a0M-E<\/span><\/span>,\u00a0et al<\/span>.\u00a0The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway<\/span>.\u00a0Nat Commun<\/em><\/span>.\u00a02016<\/span>;7<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/ncomms12700<\/span>.<\/p>\r\n
73.<\/span>\u00a0Koivunen<\/span>\u00a0P<\/span><\/span>,\u00a0Lee<\/span>\u00a0S<\/span><\/span>,\u00a0Duncan<\/span>\u00a0CG<\/span><\/span>,\u00a0et al<\/span>.\u00a0Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation<\/span>.\u00a0Nature<\/em><\/span>.\u00a02012<\/span>;483<\/span>:484<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nature10898<\/span>.<\/p>\r\n
74.<\/span>\u00a0Du<\/span>\u00a0X<\/span><\/span>,\u00a0Hu<\/span>\u00a0H<\/span><\/span>.\u00a0The roles of 2-Hydroxyglutarate<\/span>.\u00a0Front Cell Dev Biol<\/em><\/span>.\u00a02021<\/span>;9<\/span>:651317<\/span>.\u00a0DOI<\/span>:\u00a010.3389\/fcell.2021.651317<\/span>.<\/p>\r\n
75.<\/span>\u00a0Im<\/span>\u00a0AP<\/span><\/span>,\u00a0Sehgal<\/span>\u00a0AR<\/span><\/span>,\u00a0Carroll<\/span>\u00a0MP<\/span><\/span>,\u00a0et al<\/span>.\u00a0DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: Associations with prognosis and potential treatment strategies<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02014<\/span>;28<\/span>:1774<\/span>\u201383. <\/span>DOI<\/span>:\u00a010.1038\/leu.2014.124<\/span>.<\/p>\r\n
76.<\/span>\u00a0Paschka<\/span>\u00a0P<\/span><\/span>,\u00a0Schlenk<\/span>\u00a0RF<\/span><\/span>,\u00a0Gaidzik<\/span>\u00a0VI<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02010<\/span>;28<\/span>:3636<\/span>\u201343<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2010.28.3762<\/span>.<\/p>\r\n
77.<\/span>\u00a0Papaemmanuil<\/span>\u00a0E<\/span><\/span>,\u00a0Gerstung<\/span>\u00a0M<\/span><\/span>,\u00a0Bullinger<\/span>\u00a0L<\/span><\/span>,\u00a0et al<\/span>.\u00a0Genomic classification and prognosis in acute myeloid leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02016<\/span>;374<\/span>:2209<\/span>\u201321<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1516192<\/span>.<\/p>\r\n
78.<\/span>\u00a0Lachowiez<\/span>\u00a0CA<\/span><\/span>,\u00a0Reville<\/span>\u00a0PK<\/span><\/span>,\u00a0Kantarjian<\/span>\u00a0H<\/span><\/span>,\u00a0et al<\/span>.\u00a0Contemporary outcomes in IDH\u2010mutated acute myeloid leukemia: The impact of co\u2010occurring NPM1 mutations and venetoclax\u2010based treatment<\/span>.\u00a0Am J Hematol<\/em><\/span>.\u00a02022<\/span>;97<\/span>:1443<\/span>\u201352<\/span>.\u00a0DOI<\/span>:\u00a010.1002\/ajh.26694<\/span>.<\/p>\r\n
79.<\/span>\u00a0Middeke<\/span>\u00a0JM<\/span><\/span>,\u00a0Metzeler<\/span>\u00a0KH<\/span><\/span>,\u00a0R\u00f6llig<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Differential impact of IDH1\/2 mutational subclasses on outcome in adult AML: Results from a large multicenter study<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02022<\/span>;6<\/span>:1394<\/span>\u2013405<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2021004934<\/span>.<\/p>\r\n
80.<\/span>\u00a0Zarnegar-Lumley<\/span>\u00a0S<\/span><\/span>,\u00a0Alonzo<\/span>\u00a0TA<\/span><\/span>,\u00a0Gerbing<\/span>\u00a0RB<\/span><\/span>,\u00a0et al<\/span>.\u00a0Characteristics and prognostic impact of IDH mutations in AML: A COG, SWOG, and ECOG analysis<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02023<\/span>;7<\/span>:5941<\/span>\u201353<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2022008282<\/span>.<\/p>\r\n
81.<\/span>\u00a0Patel<\/span>\u00a0JP<\/span><\/span>,\u00a0G\u00f6nen<\/span>\u00a0M<\/span><\/span>,\u00a0Figueroa<\/span>\u00a0ME<\/span><\/span>,\u00a0et al<\/span>.\u00a0Prognostic relevance of integrated genetic profiling in acute myeloid leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02012<\/span>;366<\/span>:1079<\/span>\u201389<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1112304<\/span>.<\/p>\r\n
82.<\/span>\u00a0Duchmann<\/span>\u00a0M<\/span><\/span>,\u00a0Micol<\/span>\u00a0J-B<\/span><\/span>,\u00a0Duployez<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: An ALFA study<\/span>.\u00a0Blood<\/em><\/span>.\u00a02021<\/span>;137<\/span>:2827<\/span>\u201337<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2020010165<\/span>.<\/p>\r\n
83.<\/span>\u00a0Tazi<\/span>\u00a0Y<\/span><\/span>,\u00a0Arango-Ossa<\/span>\u00a0JE<\/span><\/span>,\u00a0Zhou<\/span>\u00a0Y<\/span><\/span>,\u00a0et al<\/span>.\u00a0Unified classification and risk-stratification in acute myeloid leukemia<\/span>.\u00a0Nat Commun<\/em><\/span>.\u00a02022<\/span>;13<\/span>:4622<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41467-022-32103-8<\/span>.<\/p>\r\n
84.<\/span>\u00a0Wagner<\/span>\u00a0K<\/span><\/span>,\u00a0Damm<\/span>\u00a0F<\/span><\/span>,\u00a0G\u00f6hring<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP Rs11554137 is an adverse prognostic factor<\/span>.\u00a0J Clin Oncol. <\/em><\/span>2010<\/span>;28<\/span>:2356<\/span>\u201364<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2009.27.6899<\/span>.<\/p>\r\n
85.<\/span>\u00a0Xu<\/span>\u00a0Q<\/span><\/span>,\u00a0Li<\/span>\u00a0Y<\/span><\/span>,\u00a0Lv<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Correlation between Isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: A systematic review and meta-analysis<\/span>.\u00a0Clin Cancer Res<\/em><\/span>.\u00a02017<\/span>;23<\/span>:4511<\/span>\u201322. <\/span>DOI<\/span>:\u00a010.1158\/1078-0432.CCR-16-2628<\/span>.<\/p>\r\n
86.<\/span>\u00a0Yamaguchi<\/span>\u00a0S<\/span><\/span>,\u00a0Iwanaga<\/span>\u00a0E<\/span><\/span>,\u00a0Tokunaga<\/span>\u00a0K<\/span><\/span>,\u00a0et al<\/span>.\u00a0IDH 1 and IDH 2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM 1 mutation<\/span>.\u00a0Eur J Haematol<\/em><\/span>.\u00a02014<\/span>;92<\/span>:471<\/span>\u20137<\/span>.\u00a0DOI<\/span>:\u00a010.1111\/ejh.12271<\/span>.<\/p>\r\n
87.<\/span>\u00a0Dunlap<\/span>\u00a0JB<\/span><\/span>,\u00a0Leonard<\/span>\u00a0J<\/span><\/span>,\u00a0Rosenberg<\/span>\u00a0M<\/span><\/span>,\u00a0et al<\/span>.\u00a0The combination of NPM1, DNMT3A, and IDH1\/2 mutations leads to inferior overall survival in AML<\/span>.\u00a0American J Hematol<\/em><\/span>.\u00a02019<\/span>;94<\/span>:913<\/span>\u201320<\/span>.\u00a0DOI<\/span>:\u00a010.1002\/ajh.25517<\/span>.<\/p>\r\n
88.<\/span>\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0Propert<\/span>\u00a0KJ<\/span><\/span>,\u00a0Loren<\/span>\u00a0AW<\/span><\/span>,\u00a0et al<\/span>.\u00a0Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia<\/span>.\u00a0Blood<\/em><\/span>.\u00a02013<\/span>;121<\/span>:4917<\/span>\u201324<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2013-03-493197<\/span>.<\/p>\r\n
89.<\/span>\u00a0Janin<\/span>\u00a0M<\/span><\/span>,\u00a0Mylonas<\/span>\u00a0E<\/span><\/span>,\u00a0Saada<\/span>\u00a0V<\/span><\/span>,\u00a0et al<\/span>.\u00a0Serum 2-hydroxyglutarate production in IDH1- and IDH2-mutated de novo acute myeloid leukemia: A study by the Acute Leukemia French Association group<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02014<\/span>;32<\/span>:297<\/span>\u2013305<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2013.50.2047<\/span>.<\/p>\r\n
90.<\/span>\u00a0Rohle<\/span>\u00a0D<\/span><\/span>,\u00a0Popovici-Muller<\/span>\u00a0J<\/span><\/span>,\u00a0Palaskas<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells<\/span>.\u00a0Science<\/em><\/span>.\u00a02013<\/span>;340<\/span>:626<\/span>\u201330<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1236062<\/span>.<\/p>\r\n
91.<\/span>\u00a0Wang<\/span>\u00a0F<\/span><\/span>,\u00a0Travins<\/span>\u00a0J<\/span><\/span>,\u00a0DeLaBarre<\/span>\u00a0B<\/span><\/span>,\u00a0et al<\/span>.\u00a0Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation<\/span>.\u00a0Science<\/em><\/span>.\u00a02013<\/span>;340<\/span>:622<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1126\/science.1234769<\/span>.<\/p>\r\n
92.<\/span>\u00a0Okoye-Okafor<\/span>\u00a0UC<\/span><\/span>,\u00a0Bartholdy<\/span>\u00a0B<\/span><\/span>,\u00a0Cartier<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0New IDH1 mutant inhibitors for treatment of acute myeloid leukemia<\/span>.\u00a0Nat Chem Biol<\/em><\/span>.\u00a02015<\/span>;11<\/span>:878<\/span>\u201386<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/nchembio.1930<\/span>.<\/p>\r\n
93.<\/span>\u00a0Kats<\/span>\u00a0LM<\/span><\/span>,\u00a0Vervoort<\/span>\u00a0SJ<\/span><\/span>,\u00a0Cole<\/span>\u00a0R<\/span><\/span>,\u00a0et al<\/span>.\u00a0A pharmacogenomic approach validates AG-221 as an effective and on-target therapy in IDH2 mutant AML<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02017<\/span>;31<\/span>:1466<\/span>\u201370<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/leu.2017.84<\/span>.<\/p>\r\n
94.<\/span>\u00a0Yen<\/span>\u00a0K<\/span><\/span>,\u00a0Travins<\/span>\u00a0J<\/span><\/span>,\u00a0Wang<\/span>\u00a0F<\/span><\/span>,\u00a0et al<\/span>.\u00a0AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations<\/span>.\u00a0Cancer Discov<\/em><\/span>.\u00a02017<\/span>;7<\/span>:478<\/span>\u201393<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/2159-8290.CD-16-1034<\/span>.<\/p>\r\n
95.<\/span>\u00a0Chaturvedi<\/span>\u00a0A<\/span><\/span>,\u00a0Herbst<\/span>\u00a0L<\/span><\/span>,\u00a0Pusch<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Pan-mutant-IDH1 inhibitor Bay1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02017<\/span>;31<\/span>:2020<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/leu.2017.46<\/span>.<\/p>\r\n
96.<\/span>\u00a0Clinicaltrials.gov<\/span>.\u00a0Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation. ClinicalTrials.gov identifier: NCT02074839<\/span>.\u00a02023<\/span>.\u00a0Available at<\/span>:\u00a0www.clinicaltrials.gov\/study\/NCT02074839<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
97.<\/span>\u00a0Clinicaltrials.gov<\/span>.\u00a0Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation. ClinicalTrials.gov identifier: NCT02719574<\/span>.\u00a02024<\/span>.\u00a0Available at<\/span>:\u00a0 https:\/\/clinicaltrials.gov\/study\/NCT02719574<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0February<\/span>\u00a02024<\/span>).<\/p>\r\n
98.<\/span>\u00a0de Botton<\/span>\u00a0S<\/span><\/span>,\u00a0Fenaux<\/span>\u00a0P<\/span><\/span>,\u00a0Yee<\/span>\u00a0K<\/span><\/span>,\u00a0et al<\/span>.\u00a0Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02023<\/span>;7<\/span>:3117<\/span>\u201327<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2022009411<\/span>.<\/p>\r\n
99.<\/span>\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0Stein<\/span>\u00a0EM<\/span><\/span>,\u00a0de Botton<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02018<\/span>;378<\/span>:2386<\/span>\u201398<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1716984<\/span>.<\/p>\r\n
100.<\/span>\u00a0Choe<\/span>\u00a0S<\/span><\/span>,\u00a0Wang<\/span>\u00a0H<\/span><\/span>,\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0et al<\/span>.\u00a0Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02020<\/span>;4<\/span>:1894<\/span>\u2013905<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2020001503<\/span>.<\/p>\r\n
101.<\/span>\u00a0Roboz<\/span>\u00a0GJ<\/span><\/span>,\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0Stein<\/span>\u00a0EM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia<\/span>.\u00a0Blood<\/em><\/span>.\u00a02020<\/span>;135<\/span>:463<\/span>\u201371<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2019002140<\/span>.<\/p>\r\n
102.<\/span>\u00a0Montesinos<\/span>\u00a0P<\/span><\/span>,\u00a0Recher<\/span>\u00a0C<\/span><\/span>,\u00a0Vives<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02022<\/span>;386<\/span>:1519<\/span>\u201331<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa2117344<\/span>.<\/p>\r\n
103.<\/span>\u00a0De Botton<\/span>\u00a0S<\/span><\/span>,\u00a0Montesinos<\/span>\u00a0P<\/span><\/span>,\u00a0Vives Polo<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Updated efficacy and safety data from the AGILE study in patients with newly diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02023<\/span>;41<\/span>:7012<\/span>\u20137012<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2023.41.16_suppl.7012<\/span>.<\/p>\r\n
104.<\/span>\u00a0Clinicaltrials.Gov<\/span>.\u00a0Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE). ClinicalTrials.gov identifier: NCT03173248<\/span>.\u00a02024<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/study\/NCT03173248<\/a><\/span>\u00a0(Date last accessed: <\/span>21 <\/span>February<\/span>\u00a02024<\/span>).<\/p>\r\n
105.<\/span>\u00a0De Botton<\/span>\u00a0S<\/span><\/span>,\u00a0Choe<\/span>\u00a0S<\/span><\/span>,\u00a0Marchione<\/span>\u00a0DM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Molecular characterization of clinical response in patients with newly diagnosed acute myeloid leukemia treated with Ivosidenib + Azacitidine compared to placebo + Azacitidine<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02022<\/span>;40<\/span>:7019<\/span>\u20137019<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2022.40.16_suppl.7019<\/span>.<\/p>\r\n
106.<\/span>\u00a0Lin<\/span>\u00a0J<\/span><\/span>,\u00a0Lu<\/span>\u00a0W<\/span><\/span>,\u00a0Caravella<\/span>\u00a0JA<\/span><\/span>,\u00a0et al<\/span>.\u00a0Discovery and optimization of quinolinone derivatives as potent, selective, and orally bioavailable mutant Isocitrate dehydrogenase 1 (mIDH1) inhibitors<\/span>.\u00a0J Med Chem<\/em><\/span>.\u00a02019<\/span>;62<\/span>:6575<\/span>\u201396. <\/span>DOI<\/span>:\u00a010.1021\/acs.jmedchem.9b00362<\/span>.<\/p>\r\n
107.<\/span>\u00a0Caravella<\/span>\u00a0JA<\/span><\/span>,\u00a0Lin<\/span>\u00a0J<\/span><\/span>,\u00a0Diebold<\/span>\u00a0RB<\/span><\/span>,\u00a0et al<\/span>.\u00a0Structure-based design and identification of FT-2102 (olutasidenib), a potent mutant-selective IDH1 inhibitor<\/span>.\u00a0J Med Chem<\/em><\/span>.\u00a02020<\/span>;63<\/span>:1612<\/span>\u201323<\/span>.\u00a0DOI<\/span>:\u00a010.1021\/acs.jmedchem.9b01423<\/span>.<\/p>\r\n
108.<\/span>\u00a0Reinbold<\/span>\u00a0R<\/span><\/span>,\u00a0Hvinden<\/span>\u00a0IC<\/span><\/span>,\u00a0Rabe<\/span>\u00a0P<\/span><\/span>,\u00a0et al<\/span>.\u00a0Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors<\/span>.\u00a0Nat Commun<\/em><\/span>.\u00a02022<\/span>;13<\/span>:4785<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41467-022-32436-4<\/span>.<\/p>\r\n
109.<\/span>\u00a0Watts<\/span>\u00a0JM<\/span><\/span>,\u00a0Baer<\/span>\u00a0MR<\/span><\/span>,\u00a0Yang<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0Olutasidenib alone or with\u00a0a<\/span>zacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: Phase 1 results of a phase 1\/2 trial<\/span>.\u00a0Lancet Haematol<\/em><\/span>.\u00a02023<\/span>;10<\/span>:e46<\/span>\u201358. <\/span>DOI<\/span>:\u00a010.1016\/S2352-3026(22)00292-7<\/span>.<\/p>\r\n
110.<\/span>\u00a0Cortes<\/span>\u00a0JE<\/span><\/span>,\u00a0Esteve<\/span>\u00a0J<\/span><\/span>,\u00a0Bajel<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Olutasidenib (FT-2102) in combination with azacitidine induces durable complete remissions in patients with mIDH1 acute myeloid leukemia<\/span>.\u00a0Blood<\/em><\/span>.\u00a02021<\/span>;138<\/span>:698<\/span>\u2013698<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2021-144905<\/span>.<\/p>\r\n
111.<\/span>\u00a0Jeng<\/span>\u00a0MY<\/span><\/span>,\u00a0Dutta<\/span>\u00a0R<\/span><\/span>,\u00a0Tan<\/span>\u00a0IT<\/span><\/span>,\u00a0et al<\/span>.\u00a0Improved outcomes of octogenarians and nonagenarians with acute myeloid leukemia in the era of novel therapies<\/span>.\u00a0Am J Hematol<\/em><\/span>.\u00a02020<\/span>;95<\/span>:11<\/span>.\u00a0DOI<\/span>:\u00a010.1002\/ajh.25949<\/span>.<\/p>\r\n
112.<\/span>\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0Stein<\/span>\u00a0AS<\/span><\/span>,\u00a0Stein<\/span>\u00a0EM<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mutant isocitrate dehydrogenase 1 inhibitor ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02021<\/span>;39<\/span>:57<\/span>\u201365<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.20.01632<\/span>.<\/p>\r\n
113.<\/span>\u00a0Lachowiez<\/span>\u00a0CA<\/span><\/span>,\u00a0Loghavi<\/span>\u00a0S<\/span><\/span>,\u00a0Zeng<\/span>\u00a0Z<\/span><\/span>,\u00a0et al<\/span>.\u00a0A phase IB\/II study of ivosidenib with venetoclax \u00b1 azacitidine in IDH1-mutated myeloid malignancies<\/span>.\u00a0Blood Cancer Discov<\/em><\/span>.\u00a02023<\/span>;4<\/span>:276<\/span>\u201393<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/2643-3230.BCD-22-0205<\/span>.<\/p>\r\n
114.<\/span>\u00a0Stein<\/span>\u00a0EM<\/span><\/span>,\u00a0DiNardo<\/span>\u00a0CD<\/span><\/span>,\u00a0Fathi<\/span>\u00a0AT<\/span><\/span>,\u00a0et al<\/span>.\u00a0Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: A phase 1 study<\/span>.\u00a0Blood<\/em><\/span>.\u00a02021<\/span>;137<\/span>:1792<\/span>\u2013803<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2020007233<\/span>.<\/p>","wpcf-article_received_date":"20241226","wpcf-article_accepted_date":"20240201","wpcf-article_published_online":"20240307","wpcf-podcast":"","wpcf-ogg":"","wpcf-article_end_page":"","wpcf-article_start_page":"","wpcf-acknowledgements":"","wpcf-errata_pdf":"","wpcf-article_flipper_image":"","wpcf-corrected_online":null,"wpcf-supplementary_information":"","wpcf-article_highlight_pdf":"","data_availability":"
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Data sharing is not applicable to this article as no datasets were generated or analyzed during the writing of this article.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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