Dr. Westin on Second-line CAR T-cell Therapy in Relapsed/Refractory DLBCL

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Partner | Cancer Centers | <b>The University of Texas MD Anderson Cancer Center</b>

Jason Westin, MD, FACP, discusses reasons to refer patients with diffuse large B-cell lymphoma to second-line CAR T-cell therapy, CAR T-cell eligibility criteria, and high-risk disease features that may further support the use of CAR T-cell therapy in the second line, rather than chemotherapy.

Jason Westin, MD, FACP, director, Lymphoma Clinical Research, section chief, Aggressive Lymphoma, leader, Diffuse Large B-cell Lymphoma Research Team, associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses reasons to refer patients with diffuse large B-cell lymphoma (DLBCL) to second-line CAR T-cell therapy, CAR T-cell eligibility criteria, and high-risk disease features that may further support the use of CAR T-cell therapy in the second line, rather than chemotherapy.

Dr. Westin on the Benefits of Early CAR T-cell Therapy Referral

Referring eligible patients with DLBCL for CAR T-cell therapy in the second line can help them avoid the toxicities and potential harm that can come from chemotherapy, Westin says. Historically, many patients received 1 or 2 cycles of intensive chemotherapy in the second line before being referred to a stem cell transplant center for a transplant evaluation, Westin explains. However, as the second-line standard of care has shifted to CAR T-cell therapy for patients who relapse within 12 months of their first-line therapy, referring patients to CAR T-cell therapy early, before their disease symptoms progress or they require urgent chemotherapy, will provide the best outcomes with CAR T-cell therapy, Westin emphasizes.

Dr. Westin on Identifying Eligible Patients for CAR T-cell Therapy

Patient eligibility for second-line CAR T-cell therapy is in part defined by the FDA approvals of axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi), regulatory decisions that were respectively based on data from the phase 3 ZUMA-7 (NCT03391466) and TRANSFORM (NCT03575351) studies, which enrolled patients with DLBCL who were fit for CAR T and had relapsed or refractory disease within 12 months of their initial treatment, Westin says. More patients with relapsed disease are now eligible for curative-intent CAR T-cell therapy than have historically been eligible for stem cell transplant, as there is no age, creatinine clearance, or ejection fraction cutoff, Westin notes. CAR T-cell centers can evaluate the CAR T fitness of all patients referred, Westin explains.

Dr. Westin on High-risk Features that Influence DLBCL Treatment Decisions

Historically, patients with DLBCL who are refractory to or relapse early after first-line therapies have been difficult to treat, Westin says. If patients do not respond to first-line chemotherapy regimens such as R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride), the chances of them responding to additional chemotherapy in the second line are low, Westin notes. These patients should be referred to a CAR T-cell center as quickly as possible, so they can potentially benefit from CAR T-cell therapy in the second line instead, Westin concludes.