Dr Shah on Safety and Efficacy Outcomes With Obe-Cel in Older R/R ALL

“Here we can show that in an older patient population who wasn't transplanted, we were seeing these patients receive CAR T-cell therapy as definitive therapy, [and] the outcome was excellent. We weren't seeing a higher rate of severe infections. We weren't seeing a higher mortality rate. We were seeing the patients do quite well."

Bijal Shah, MD, MS, an associate member in the Department of Malignant Hematology at Moffitt Cancer Center, discussed the clinical implications of key safety and efficacy findings from a post hoc analysis of the phase 1b/2 FELIX trial (NCT04404660) investigating obecabtagene autoleucel (obe-cel; Aucatzyl) in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

The most critical point to emphasize about these findings is that obe-cel demonstrated a favorable safety profile in patients with relapsed or refractory B-ALL, including those of advanced age, Shah began. Historically, there has been considerable hesitation regarding the use of intensive or cellular therapies in older adults with acute leukemias, often due to referral bias, he said. Many older patients may never present to tertiary centers and instead opt for hospice care at diagnosis, he noted. This raises concerns about whether such patients are underrepresented in clinical trials, he emphasized. Importantly, the FELIX trial showed that older adults who were not transplant candidates could still receive CAR T-cell therapy as definitive treatment, with encouraging outcomes, according to Shah.

In terms of safety, there was no observed increase in severe infections, no excess treatment-related mortality, and no alarming safety signals regarding cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome in older patients compared with younger patients, Shah explained. This is noteworthy given that older adults are often more susceptible to neurotoxicity, he added. The data suggest that CAR T-cell therapy in this population is well tolerated and feasible, even in settings where travel distance and logistics might otherwise dissuade patients from pursuing aggressive therapy, he reported.

Efficacy outcomes were equally impressive, Shah continued. A substantial portion of patients over 65 years of age achieved durable complete response without the need for additional therapy, which far exceeds historical expectations, he contextualized. Typically, survival rates for older patients with relapsed or refractory ALL are extremely poor, often in the single digits, he continued. For example, prior studies of patients over 70 years of age demonstrated that even with modifications to chemotherapy or the addition of novel agents like inotuzumab ozogamicin (Besponsa) and blinatumomab (Blincyto), long-term survival remained limited due to treatment-related toxicities, he said.

In contrast, in FELIX, obe-cel provided both efficacy and tolerability, establishing itself as a viable treatment option for older, frailer patients who historically have had few effective therapies, Shah highlighted. The message from these findings is clear: CAR T-cell therapy with obe-cel is a transformative treatment option for older adults with relapsed/refractory B-ALL, shifting the treatment paradigm in a setting of significant unmet need, Shah concluded.