CAR-T demonstrates efficacy as second-line therapy for transplant-ineligible lymphoma
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CHICAGO — Second-line therapy with lisocabtagene maraleucel induced initial complete remission among more than half of patients with relapsed or refractory transplant-ineligible large B-cell lymphoma, results from a phase 2 trial showed.
A primary analysis from the PILOT study — presented at ASCO Annual Meeting — revealed low incidence of high-grade treatment-related cytokine release syndrome and neurotoxicity after a single dose of the cell therapy.
Background
Lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) — a CD19-directed chimeric antigen receptor T-cell therapy commonly called liso-cel — is approved in the United States for adults with relapsed or refractory diffuse large B-cell lymphoma who received two or more lines of systemic therapy.
High-dose chemotherapy followed by hematopoietic stem cell transplant is standard for patients with relapsed or refractory disease, but the regimen leads to lasting remissions for fewer than half of patients. In addition, a large number of patients with relapsed or refractory disease are ineligible for HSCT due to age or comorbidities.
Consequently, there is a considerable need for a more effective treatment, according to Leo I. Gordon, MD, FACP, co-director of the hematologic malignancies program at Northwestern University Feinberg School of Medicine, medical director of John and Lillian Mathews Center for Cellular Therapy at Robert H. Lurie Comprehensive Cancer Center and a member of the Healio | Cell Therapy Next Peer Perspective Board.
“The purpose of this trial was to take a treatment that had been shown to be beneficial in the third line and beyond and apply it as earlier therapy, specifically in a group of patients already treated for large B-cell lymphoma who relapsed but who were not candidates for transplant,” he told Healio. “We wanted to see if it was safe and effective to provide CAR T-cell therapy instead of transplant in this group of patients.”
The goal of subsequent therapy for most patients with transplant-ineligible progressive disease typically is palliative, Gordon said. Providing CAR-T as earlier therapy for these patients should, therefore, improve outcomes, he added.
“If the goal of transplant is to provide a curative therapy, then the goal of providing CAR-T to these patients should be curative, as well,” Gordon said.
Methodology
The multicenter PILOT study included 61 patients (median age, 74 years; range, 53-84; 61% male) with relapsed or refractory B-cell lymphoma. All study participants experienced disease progression after first-line therapy and were ineligible for high-dose chemotherapy and HSCT.
Patients received lymphodepletion chemotherapy followed by a single infusion of liso-cel at a target dose of 100 × 106 CAR T cells.
Overall response rate served as the primary endpoint. Secondary endpoints included safety and other measurements of treatment efficacy.
Median follow-up was 12.3 months (range, 1.2-26.5).
Key findings
Liso-cel conferred an ORR of 80% (95% CI, 68.2-89.4), with a complete response rate of 54% (95% CI, 40.8-66.9).
Investigators reported a 12.09 month (95% CI, 6.2-not reached) median duration of response among all patients, and a 21.65 months (95% CI, 12.09-not reached) median duration among those who achieved compete response.
Results showed median PFS of 9.03 months (95% CI, 4.17-not reached). Median OS had not been reached (95% CI, 17.28-not reached).
Twenty-three patients (38%) experienced treatment-related CRS, with one grade 3 case.
Nineteen patients (31%) developed treatment-related neurotoxicity, including three patients (5%) with grade 3 symptoms. No cases of grade 4 or grade 5 CRS or neurotoxicity occurred.
The most common grade 3 or higher treatment-related adverse events included neutropenia (48%), leukopenia (21%) and thrombocytopenia (20%).
Clinical implications
The results thus far showed ORRs and complete response rates “higher than what would have been expected with any other treatment in this group of patients,” Gordon said. Nevertheless, further follow-up is needed to determine the durability of these outcomes, he said.
“The overall toxicity profile for CAR-T among this 70-plus-year-old group of patients was more favorable than autologous stem cell transplant,” Gordon said.
“I believe that liso-cel will have a positive impact on clinical care,” he added. “These data are promising, but we can't yet say that [CAR-T] has replaced the standard of care for this typically older group of patients.”
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Sehgal A, et al. Abstract 7062. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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