Second-Line CAR-T Impresses in Transplant-Ineligible Large B-Cell Lymphoma

Treatment with second-line lisocabtagene maraleucel (liso-cel; Breyanzi) yielded a response rate of 80% for patients with relapsed or refractory large B-cell lymphoma (LBCL) who were not candidates for hematopoietic stem cell transplant, the phase II PILOT study showed.

Among 61 evaluable patients with PET-positive disease, 54% achieved a complete response with the chimeric antigen receptor (CAR) T-cell therapy and 26% had partial responses over a median follow-up of 12.3 months, reported Alison Sehgal, MD, of the University of Pittsburgh Medical Center in Pennsylvania, and colleagues in Lancet Oncology.

The standard of care for patients with relapsed or refractory LBCL after first-line therapy is salvage chemotherapy followed by transplant. However, no more than half of patients are eligible for transplant, with the rest limited to non-curative treatments, such as platinum-based regimens or investigational therapies in clinical trials, due to age, comorbidities, or low performance status, Sehgal and team noted.

“Thus, there is an important unmet need for effective second-line treatments for patients with relapsed or refractory disease for whom hematopoietic stem cell transplant is not intended and who have no curative option,” they wrote.

These findings are in line with those from an interim analysis of the phase III TRANSFORM trial, which showed superior outcomes with liso-cel compared with standard of care in the second line followed by transplant in patients with relapsed or refractory LBCL.

In June, the FDA approved liso-cel as a second-line treatment for relapsed or refractory LBCL based on the results from both the PILOT and TRANSFORM trials.

In other findings from PILOT, the median progression-free survival (PFS) was 9.03 months at a median follow-up of 13 months, and the median overall survival (OS) was not reached at a median follow-up of 17.6 months. The median duration of response was 12.09 months at a median follow-up of 15.5 months.

For those patients who had a complete response, the median PFS was 22.6 months and the median OS was not reached, while the median duration of response was 21.7 months.

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (48% of patients), leukopenia (21%), and thrombocytopenia (20%). Serious TEAEs related to liso-cel were reported in 21% of patients, with no treatment-related deaths. Cytokine release syndrome occurred in 38% of patients, and neurological events in 31%.

For this open-label study, Sehgal and team enrolled 74 patients who had received first-line treatment containing an anthracycline and a CD20-targeted agent and were deemed non-candidates for transplant.

All patients underwent leukapheresis for manufacture of CAR T cells, and 61 received liso-cel from July 2018 to September 2021 at 18 U.S. sites.

Of the 61 patients who received the CAR T-cell therapy, median age was 74 years, 39% were women, 26% had an Eastern Cooperative Oncology Group performance status of 2, 54% had refractory disease, 21% relapsed within 1 year of first-line therapy, and 25% relapsed after 12 months of first-line therapy.

Sehgal and colleagues acknowledged several limitations to the the study, including the fact that the median follow-up for OS was relatively short at 17.6 months, and longer follow-up is needed to determine the survival benefit with liso-cel in this patient population.

Furthermore, targeted therapies such as tafasitamab combined with lenalidomide (Revlimid) and polatuzumab vedotin (Polivy) combined with bendamustine and rituximab have shown efficacy and tolerable safety profiles as second-line or later treatment in patients with relapsed or refractory LBCL not eligible for transplant, the authors noted.

“If additional therapies currently being evaluated in this patient population show efficacy in the second-line setting, future comparative studies with lisocabtagene maraleucel might be necessary to determine the relative clinical benefit to patients,” they wrote.