Diffuse large B-cell lymphoma.

The FDA has granted approval to lisocabtagene maraleucel (liso-cel) (Breyanzi^®, Bristol Myers Squibb™) for treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after one prior therapy who have become R/R within 12 months of first-line therapy, or who have become R/R after the first line of therapy and are not eligible for hematopoietic stem cell transplant (HSCT). The approval was based on the phase 3 TRANSFORM trial (NCT03575351) and the phase 2 PILOT study (NCT03483103).

"Patients with LBCL primary refractory to or relapsed within 12 months after first-line therapy may have poor outcomes with standard of care, including salvage chemotherapy and allogeneic stem cell transplant, which underscores a critical unmet need," wrote Manali Kamdar, Clinical Director of Lymphoma Services at University of Colorado Medicine, and colleagues, about their presentation of the TRANSFORM study (NCT03575351). "In the TRANSFORM study, liso-cel demonstrated statistically significant and clinically meaningful improvement in the primary end point, event-free survival (EFS), as well as in key secondary efficacy end points compared with standard of care."

The safety and efficacy of liso-cel were evaluated in the phase 3, open-label, TRANSFORM trial, which randomized 184 patients 1:1 to receive either standard of care or liso-cel treatment. The primary end point of this study was event-free survival, which saw a significant result with liso-cel treatment increasing event-free survival by four times compared with the standard of care (10.1 months versus 2.3 months). Secondary end points included complete response rate and progression-free survival, which both saw significant results. Complete response was seen in 66% of patients being treated with liso-cel compared with 39% in the standard of care arm; and progression-free survival was doubled in those receiving liso-cel compared with those receiving standard of care (14.8 months versus 5.7 months).

Safety and efficacy were also measured in the phase 2, open-label, PILOT study which enrolled 61 patients who were R/R to a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma and were ineligible for HSCT. The end points in this study showed significant results, as well. The primary end point of overall response rate was 80% in patients receiving lico-cel. Secondary end points included complete response, recorded at a rate of 54%; median time to complete response, which was 1 month; and duration of response, which was a median of 11.2 months, with overall duration of response not met in patients who achieved a complete response.

Liso-cel is only available under a Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of fatal or life-threatening cytokine release syndrome (CRS) and neurologic toxicities. In studies of liso-cel treatment of LBCL, CRS occurred in 46% of patients, and neurologic toxicities occurred in 27%. The most common nonlaboratory adverse reactions seen in ≥30% of patients were fever, CRS, fatigue, musculoskeletal pain, and nausea. The most common grade 3-4 laboratory abnormalities seen in ≥30% of patients included lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.

"These preliminary safety and efficacy data from the ongoing phase 2 PILOT study suggest that liso-cel can be successfully administered, including in the outpatient setting, as second-line therapy in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who were ineligible for high-dose chemotherapy and HSCT, by prespecified criteria," concluded Alison Sehgal, Assistant Professor of Medicine at the University of Pittsburgh School of Medicine, and colleagues, in their presentation of the PILOT study (NCT03483103).

The recommended dosage of lisocabtagene maraleucel for second-line therapy is 90 to 110x10⁶ CAR-positive T cells with a 1:1 ratio of CD4 and CD8 components following lymphodepleting therapy.

For More Information

Sehgal A, Hoda D, Riedell P, et al (2022). Lisocabtagene maraleucel as second-line therapy for R/R large B-cell lymphoma in patients not intended for hematopoietic stem cell transplantation: primary analysis from the phase 2 PILOT study. J Clin Oncol (ASCO Annual Meeting Abstracts), (suppl_16). Abstract 7062. DOI:10.1200/JCO.2022.40.16_suppl.7062

Kamdar M, Solomon SR, Arnason JE, et al (2021). Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor T-cell therapy, versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: results from the randomized phase 3 Transform study. ASH Annual Meeting. Abstract 91.

Bristol Myers Squibb™ (2022). Data from phase 2 PILOT study of Bristol Myers Squibb's CAR T-cell therapy Breyanzi^® show substantial durable responses in patients with refractory or relapsed large B-cell lymphoma after first-line therapy. Available at: https://news.bms.com/news/details/2022/Data-from-Phase-2-PILOT-Study-of-Bristol-Myers-Squibbs-CAR-T-cell-Therapy-Breyanzi-Show-Substantial-Durable-Responses-in-Patients-with-Refractory-or-Relapsed-Large-B-cell-Lymphoma-After-First-Line-Therapy/default.aspx

Clinicaltrials.gov (2022). A study to compare the efficacy and safety of JCAR017 to standard of care in adult subjects with high-risk, transplant-eligible relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (TRANSFORM). NLM identifier: NCT03575351.

Clinicaltrials.gov (2022). Lisocabtagene maraleucel (JCAR017) as second-line therapy (TRANSCEND-PILOT-017006). NLM identifier: NCT03483103.

Breyanzi^® (lisocabtagene maraleucel) prescribing information (2022). Bristol Myers Squibb™. Available at: https://packageinserts.bms.com/pi/pi_breyanzi.pdf

Businesswire (2022). US FDA approves Bristol Myers Squibb's CAR T-cell therapy Breyanzi® for relapsed or refractory large B-cell lymphoma after one prior therapy. Available at: https://www.businesswire.com/news/home/20220427005982/en/U.S.-FDA-Approves-Bristol-Myers-Squibb%E2%80%99s-CAR-T-Cell-Therapy-Breyanzi%C2%AE-for-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy

Bristol Myers Squibb™ (2022). US FDA approves Bristol Myers Squibb's CAR T-cell therapy Breyanzi® for relapsed or refractory large B-cell lymphoma after one prior therapy. Available at: https://news.bms.com/news/details/2022/U.S.-FDA-Approves-Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzifor-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy/default.aspx

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