Dr Murthy on the Use of CAR T-Cell Therapy in Elderly or Frail Patients With B-Cell Lymphomas

Hemant S. Murthy, MD, hematologist/oncologist, physician, Mayo Clinic, discusses the evolving use of CAR T-cell therapy for elderly or frail patient populations withrelapsed/refractory B-cell lymphomas.

Murthy begins by stating that current registry studies, including a large study based in Germany, have demonstrated the feasibility of administering CAR T-cell therapy to elderly patients with B-cell lymphomas. These studies did not reveal significant variation in the frequency of treatment-related cytokine release syndrome based on age in patients with B-cell lymphomas who were treated with CAR T-cell therapy. However, elderly patients tended to experience more immune effector cell–associated neurotoxicity syndrome.

To elucidate whether CAR T-cell therapy is a viable treatment alternative for patients with aggressive relapsed/refractory B-cell lymphomas who are deemed ineligible for autologous stem cell transplant (ASCT), the open-label, phase 2 ALYCANTE trial (NCT04531046) evaluated the efficacy and safety of axicabtagene ciloleucel (Yescarta; axi-cel) in the second-line setting, Murthy details. ASCT ineligibility was largely determined by age, prior treatment with ASCT, and a Hematopoietic Cell Transplantation–specific Comorbidity Index score of 3 or higher, he expands. The ALYCANTE trial employed a broad set of exclusion criteria. This included pulmonary complications, cardiac issues, pleural effusions, and hepatitis, Murthy states.

Results demonstrated that axi-cel produced a complete metabolic response (CMR) rate of 71% at 3 months vs an expected 12% CMR rate with the standard of care based on historical controls, meeting the study's primary end point (n=44; 95% CI, 58.1%–81.8%). At 6 months, 59.7% of patients (n=37) who received axi-cel continued to exhibit a CMR. Additionally, patients experienced a treatment-related mortality rate of 9.7% with axi-cel, which was higher than the 1% to 2% rate historically associated with ASCT, Murthy reports.

Although the ALYCANTE trial shows promising results with axi-cel, it also underscores the ongoing challenge of identifying and defining which patients are ineligible for CAR T-cell therapy, Murthy emphasizes. Patient selection remains a work in progress, with ongoing studies aiming to refine this process, Murthy concludes.