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Haematology, Lymphoma
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Axicabtagene ciloleucel for the treatment of large B-cell lymphoma: Jason Westin, EHA 2023

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Published Online: Jul 14th 2023

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved to treat patients with relapsed/refractory large B-cell lymphoma. We caught up with Dr Jason Westin (The University of Texas MD Anderson Cancer Center, Houston, TX, USA) to discuss the current treatment paradigm for large B-cell lymphoma, the limitations of current therapeutic options and the mechanism of action of axi-cel.

The abstract entitled ‘PB2319 ZUMA-23: A GLOBAL, PHASE 3, RANDOMIZED CONTROLLED STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE AS FIRST-LINE THERAPY IN PATIENTS WITH HIGH-RISK LARGE B-CELL LYMPHOMA’ was presented at the EHA 2023 Congress, 8–11 and 14–15 June 2023.

Questions:

  1. What is the current treatment paradigm for large B-cell lymphoma? (0:16)
  2. What are the limitations of current therapeutic options for large B-cell lymphoma? (0:56)
  3. What is the mechanism of action of axicabtagene ciloleucel (axi-cel)? (1:42)

Disclosures: Jason Westin acts as a consultant for, has received grant/research support from, and is on the advisory board of Abbvie, ADC Therapeutics, AstraZeneca, BMS, Genentech, Genmab, Kite/Gilead, Morphosys, and Novartis.

Support: Interview and filming supported by Touch Medical Media. Interview conducted by Atiya Henry.

Filmed as a highlight of EHA 2023.

Transcript

Hi. I’m Dr Jason Westin from MD Anderson Cancer Center in Houston, Texas. I’m the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas.

What is the current treatment paradigm for large B-cell lymphoma? (0:16)

The current treatment paradigm for large B-cell lymphoma is evolving rapidly. In the first line treatment, the long standard R-CHOP has a new challenger with the approval of polatuzumab for patients with IPI 2-5, replacing vincristine. That doesn’t mean that every patient will receive that therapy, but it is an option for many patients now with the higher IPI disease. In the second line, the paradigm has shifted so that many patients should now receive CAR T-cell therapy as opposed to the old standard of platinum-based chemotherapy and autologous transplants.

What are the limitations of current therapeutic options for large B-cell lymphoma? (0:56)

The current limitations of therapeutic options for large B-cell lymphoma include that some patients are not able to tolerate things such as chemotherapy. In the first line setting, there are a number of elderly patients or patients that have medical comorbidities that are unable to tolerate treatments like R-CHOP, and therefore non-chemotherapy based approaches are needed, such as targeted therapies. We and others have pioneered using targeted therapies prior to chemotherapies, which is a very promising approach. In the second line setting, some patients can’t tolerate treatments such as autologous stem cell transplant, but more patients will be able to tolerate side effect wise CAR T-cell therapy.

What is the mechanism of action of axicabtagene ciloleucel (axi-cel)? (1:42)

The mechanism of action of axi-cel is a T-cell killing a cancer cell. We’ve had T-cells in our bodies through evolution forever, but they often struggle to identify cancer as a foreign invader and instead see it as the same team. A CAR T-cell is effectively an engineered T-cell that now can see the wolf in sheep’s clothing. It can now see the cancer cell as the enemy and can go seek and destroy. And so CAR T-cells have huge advantages, through using our own body’s defense mechanisms to now direct them in the correct direction to go after cancer and eradicate it.

Subtitles and transcript are autogenerated

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