Lisocabtagene maraleucel (liso-cel), marketed as Breyanzi, is showing promising results in treating relapsed or refractory lymphomas, according to recent data presented at the American Society of Hematology (ASH) Annual Meeting and other publications. The CD19-directed CAR T-cell therapy has demonstrated efficacy and tolerability in various lymphoma subtypes, including large B-cell lymphoma (LBCL) and marginal zone lymphoma (MZL). These findings support its use in both second-line and third-line settings, offering new hope for patients with limited treatment options.
Consistent Efficacy in Second-Line LBCL
Real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry confirm that liso-cel's efficacy and safety in second-line LBCL treatment are consistent with those observed in the pivotal TRANSFORM and PILOT trials. The study, which included 156 patients, showed that the median progression-free survival (PFS) and overall survival (OS) were not reached at a median follow-up of 6.4 months (95% CI, 6.1-6.5). The 6-month PFS and OS rates were 61% (95% CI, 52%-69%) and 87% (95% CI, 80%-92%), respectively.
Notably, the objective response rate (ORR) was 84% (95% CI, 77%-89%), with a complete response (CR) rate of 70% (95% CI, 62%-77%). These results, presented by Dr. María Silvina Odstrcil Bobillo from the University of Utah School of Medicine, support liso-cel as a second-line standard-of-care for relapsed/refractory LBCL patients, regardless of age or transplant eligibility.
Promising Results in Marginal Zone Lymphoma
In the phase 2 TRANSCEND FL trial (NCT04245839), liso-cel met its primary endpoint, demonstrating a statistically significant and clinically meaningful overall response rate (ORR) in adult patients with relapsed/refractory marginal zone lymphoma (MZL). The trial also met its key secondary endpoint of complete response (CR) rate in this cohort. According to Bristol Myers Squibb, the topline analysis showed that responses were durable, and the safety profile of liso-cel was consistent with prior findings for the CAR T-cell therapy, with no new safety signals reported.
Rosanna Ricafort, vice president at Bristol Myers Squibb, noted the need for effective treatments for MZL patients who relapse or become refractory, emphasizing that the TRANSCEND FL study supports liso-cel's potential in this setting.
Curative Potential in Third-Line LBCL
Five-year survival data from the TRANSCEND-NHL-001 trial (NCT02631044) further highlight the curative potential of liso-cel in third-line relapsed/refractory LBCL. The study, presented at the 66th ASH Annual Meeting, showed an estimated overall survival rate of 38% at 5 years. Manali Kamdar, MD, from the University of Colorado, emphasized the importance of these results, noting that patients who remain in remission at the 5-year mark after LBCL treatment are typically considered cured.
The median overall survival at the 5-year mark was 27.5 months, and the median disease-specific survival was 68 months. These findings suggest that liso-cel can offer long-term remission and potential cure for patients with advanced LBCL.
Safety and Tolerability
The safety profile of liso-cel remains consistent across different studies and patient populations. Common adverse events include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but these are generally manageable. In the CIBMTR registry study, CRS occurred in 45% of patients, with most cases being grade 1 or 2. ICANS occurred in 20% of patients, with similar low-grade severity.
Dr. Bobillo noted that the safety profile was consistent with previous reports, with most patients experiencing low-grade CRS, ICANS, prolonged cytopenia, or infections. These findings reinforce the tolerability of liso-cel, making it a viable option for a broad range of patients.
Implications for Clinical Practice
The accumulating evidence supports the use of liso-cel as an effective and well-tolerated treatment option for patients with relapsed or refractory LBCL and MZL. Its consistent efficacy in both second-line and third-line settings, along with a manageable safety profile, positions it as a valuable tool in the treatment of these challenging lymphomas. As Dr. Kamdar noted, it is crucial to refer patients to CAR-T centers as soon as possible to ensure timely access to this potentially curative therapy.
