Legend Biotech Reports Long-Term Progression-Free Survival Data for CARVYKTI® in Multiple Myeloma and Promising Early Results from New CAR-T Therapies in Solid Tumors

Legend Biotech announced positive long-term data from the CARTITUDE-1 study, revealing that 33% of relapsed/refractory multiple myeloma patients remained progression-free five years after a single CARVYKTI® infusion, with a median overall survival of 60.7 months. Subgroup analyses from the CARTITUDE-4 study also demonstrated durable progression-free and overall survival benefits with CARVYKTI® compared to standard therapies across various high-risk cytogenetic subgroups. Additionally, early Phase 1 trials for LB1908 and LB2102, targeting gastroesophageal and lung cancers, respectively, showed promising results, though CARVYKTI®'s safety profile includes risks of cytokine release syndrome and neurologic toxicities.

Analysis

Legend Biotech Corporation (LEGN) reported compelling long-term efficacy for CARVYKTI® in relapsed/refractory multiple myeloma (RRMM), with the CARTITUDE-1 study indicating that 33% of patients remained progression-free at five years and a median overall survival of 60.7 months. The CARTITUDE-4 study further demonstrated CARVYKTI®'s durable progression-free and overall survival benefits compared to standard therapies across diverse patient risk subgroups, even as early as second-line therapy. Additionally, Legend Biotech highlighted promising early Phase 1 results for its pipeline candidates, LB1908 targeting gastroesophageal cancers and LB2102 for lung cancers, suggesting potential expansion into solid tumors. However, these positive clinical outcomes are counterbalanced by significant safety concerns associated with CARVYKTI®, including high rates of cytokine release syndrome (CRS) occurring in 84% of patients and neurologic toxicities in 24%. More critically, the data revealed a numerically higher percentage of early deaths within the first 10 months in the CARVYKTI® arm (14%) compared to the control arm (12%) in the CARTITUDE-4 trial, and the emergence of secondary hematological malignancies, such as myelodysplastic syndromes and acute myeloid leukemia, in 5% of patients post-treatment. These adverse events contribute to a mixed sentiment (-0.15 overall, -0.3 for LEGN specifically) and likely influenced substantial divestitures by major institutional investors in Q1 2025; notably, RA CAPITAL MANAGEMENT L.P. liquidated its entire position, and CITADEL ADVISORS LLC reduced its holdings by 94.7%. Despite these red flags, two Wall Street firms have maintained 'Buy' or 'Overweight' ratings on LEGN in recent months.

Key Decisions for Investors

• Investors should meticulously weigh CARVYKTI®'s significant long-term efficacy in a hard-to-treat patient population against its substantial safety risks, including CRS, neurotoxicities, increased early mortality, and secondary malignancies.
• The considerable selling pressure from large institutional investors in Q1 2025, such as RA Capital and Citadel, warrants careful consideration as a potential leading indicator despite positive clinical trial results and existing buy ratings from some analysts.
• Monitor upcoming data readouts on CARVYKTI®'s safety profile, any regulatory responses to these adverse events, and continued progress in Legend Biotech's early-stage solid tumor pipeline (LB1908, LB2102) to gauge future risk-reward dynamics.