New research has confirmed the superiority of lisocabtagene maraleucel over the standard of care for the second-line treatment of primary refractory or early relapsed large B-cell lymphoma, according to data presented by lead study author Jeremy S. Abramson, MD, Associate Professor of Medicine at Harvard Medical School, and Director of the Lymphoma Program at Massachusetts General Hospital,at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition.¹

Jeremy S. Abramson, MD

At a median follow up of 17.5 months, primary analysis of the phase III TRANSFORM study demonstrated significant improvements in event-free survival, complete response rate, and progression-free survival among patients who received the chimeric antigen receptor (CAR) T-cell therapy vs the standard of care. The incidence of CAR T-cell–specific adverse events was also low, authors of the study reported.

“With 18 months of follow-up, event-free and progression-free survival rates with lisocabtagene maraleucel more than doubled those with standard care,” said Dr. Abramson. “These data support the use of lisocabtagene maraleucel as a preferred second-line treatment in patients with primary refractory or early relapsed diffuse large B-cell lymphomas.”

For patients with relapsed or refractory large B-cell lymphoma, salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation in chemosensitive patients has been the standard of care for decades. Lisocabtagene maraleucel is an autologous, CD19-directed, CAR T-cell product administered at equal target doses of CD8-positive and CD4-positive CAR T cells.

Study Methods

Patients eligible for the phase III TRANSFORM study had either primary refractory or early relapsed (within 12 months of first-line therapy) large B-cell lymphoma and were candidates for high-dose chemotherapy. All patients underwent leukapheresis prior to randomization. Patients on the standard-of-care arm received three cycles of platinum-based chemotherapy, with responders proceeding to the BEAM (carmustine, etoposide, cytarabine, melphalan) regimen and autologous stem cell transplantation. Patients in the lisocabtagene maraleucel arm could receive up to one cycle of bridging therapy with a chemotherapy regimen from the standard-of-care arm at the discretion of their treating investigator.

Results of a prespecified interim analysis of the TRANSFORM study, performed at a median follow-up of 6.7 months, previously demonstrated the superior efficacy of lisocabtagene maraleucel compared with the standard of care. At the 2022 ASH meeting, Dr. Abramson presented the event-driven primary analysis.

Improvement in Several Outcomes

As Dr. Abramson reported, 92 patients were randomly assigned to each arm. On the lisocabtagene maraleucel arm, 63% of patients received bridging chemotherapy, and 97% received lisocabtagene maraleucel infusion, with one patient receiving a nonconforming product.

With a median follow-up of 17.5 months, median event-free survival was not reached with lisocabtagene maraleucel compared with 2.4 months with the standard of care (hazard ratio [HR] = 0.356). The 18-month event-free survival rate was 52.6% with lisocabtagene maraleucel vs 20.8% with the standard of care, said Dr. Abramson, who noted that event-free survival subgroup analysis favored lisocabtagene maraleucel across all defined subgroups based on patient and disease-specific characteristics.

The best complete response rate was 74% with lisocabtagene maraleucel compared with 43% with the standard of care. The median duration of complete response was not reached for lisocabtagene maraleucel and was 9.3 months for the standard of care, with a hazard ratio favoring lisocabtagene maraleucel.

“Complete responses were likelier to be durable in patients treated with lisocabtagene maraleucel,” said Dr. Abramson, with a 60% reduction in the risk of disease progression or death favoring lisocabtagene maraleucel over the standard of care. “At 18 months, 58.2% of patients given lisocabtagene maraleucel remain progression-free compared with 28.8% of patients given the standard of care.”

Overall survival also numerically favored lisocabtagene maraleucel, with 73.1% of patients given lisocabtagene maraleucel alive at 18.5 months compared with 60.6% given the standard of care. According to Dr. Abramson, however, this difference was not statistically significant, given that two-thirds of patients randomly assigned to the standard of care crossed over to receive lisocabtagene maraleucel. After the investigators adjusted for the impact of crossover, supportive overall survival analysis showed a benefit in favor of lisocabtagene maraleucel, Dr. Abramson noted.

The most common treatment-emergent adverse events in both arms were cytopenias, although prolonged cytopenias were more common with lisocabtagene maraleucel than with the standard of care. Two patients in each arm died because of treatment-emergent adverse events. Cytokine-release syndrome occurred in 49% of patients treated with lisocabtagene maraleucel, but these events were almost entirely low grade, said Dr. Abramson.

The incidence of neurologic toxicities was also low at 11%, and four patients experienced grade 3 neurologic events. There were no grade 4 or 5 events. Dr. Abramson reported that 24% of patients received tocilizumab and 16% received corticosteroids for the management of cytokine-release syndrome and/or neurologic toxicities. 

DISCLOSURE: Dr. Abramson reported financial relationships with AbbVie, BMS, Genentech, Genmab, Janssen, Kite Pharma, Eli Lilly, MorphoSys, and Regeneron.

REFERENCE

1. Abramson JS, Solomon SR, Arnason JE, et al: Lisocabtagene maraleucel 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. 2022 ASH Annual Meeting and Exposition. Abstract 655. Presented December 11, 2022.