Legend Biotech Presents Early CARVYKTI® Data for Multiple Myeloma at ASCO and EHA

Legend Biotech Corporation announced significant findings from the Phase 2 CARTITUDE-2 Cohort D study and the Phase 3 CARTITUDE-4 study regarding CARVYKTI® (ciltacabtagene autoleucel, cilta-cel), a BCMA-targeted therapy for multiple myeloma. The results, presented at the 2024 ASCO Annual Meeting and the 2024 European Hematology Association (EHA) Congress, highlight the efficacy and safety of CARVYKTI® in patients with multiple myeloma who have had a suboptimal response to front-line autologous stem cell transplant (ASCT) and those with high-risk cytogenetic profiles.

The CARTITUDE-2 Cohort D study focused on multiple myeloma patients who did not achieve a complete response (CR) post-front-line ASCT. Findings revealed that a one-time infusion of CARVYKTI® led to deep and durable responses. Among the 17 patients treated with CARVYKTI®, a remarkable 94% achieved an overall response rate (ORR), with all responders reaching CR or better. Additionally, 80% of minimal residual disease (MRD)-evaluable patients achieved MRD negativity. The median duration of response was not reached, and the 18-month progression-free survival (PFS) and overall survival (OS) rates stood at an impressive 94%.

Dr. Melissa Alsina from H. Lee Moffitt Cancer Center emphasized the significance of these results, noting that patients with less than complete responses post-ASCT might typically experience less durable outcomes with subsequent treatments. The safety profile of CARVYKTI® was consistent with previous findings, with common grade 3 or 4 treatment-emergent adverse events (TEAEs) including neutropenia, lymphopenia, and thrombocytopenia. No cases of movement and neurocognitive treatment-emergent adverse events (MNTs) or parkinsonism were observed in the study.

Legend Biotech's Chief Medical Officer, Dr. Mythili Koneru, expressed optimism about the potential of CARVYKTI® to produce deep and durable responses earlier in the multiple myeloma treatment landscape. The company is currently conducting Phase 3 studies to explore if CARVYKTI® could benefit patients even in the frontline treatment setting.

The CARTITUDE-4 study compared CARVYKTI® with standard therapies (pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with relapsed and lenalidomide-refractory multiple myeloma. This study included a subgroup analysis of patients with functional high-risk (FHR) multiple myeloma, defined by disease progression within 18 months of ASCT or initial treatment. The analysis showed that CARVYKTI® significantly improved PFS compared to standard therapies. Specifically, CARVYKTI® demonstrated a median PFS that was not reached, compared to 17 months for the control arm, highlighting a profound improvement in disease control.

Safety data from CARTITUDE-4 were consistent with known profiles of cilta-cel, with a comparable proportion of grade 3 or higher TEAEs between the CARVYKTI® and standard therapy arms. The subgroup analysis also indicated consistently higher rates of overall responses, CR or better, and MRD negativity in the CARVYKTI® group compared to standard therapies.

Additionally, a CARTITUDE-4 subgroup analysis focusing on patients with high-risk cytogenetic profiles demonstrated favorable efficacy outcomes for CARVYKTI®, including higher overall response rates, CR rates, and MRD negativity rates, along with improved PFS compared to standard therapies. In patients with standard-risk cytogenetics, CARVYKTI® also showed a superior PFS that was not reached, compared to 20.6 months with standard therapies.

The efficacy results from these studies support the potential of CARVYKTI® as a new standard of care for patients with relapsed or refractory multiple myeloma, particularly those with high-risk cytogenetic features. The CARTITUDE-4 data also underpinned the U.S. FDA's approval of CARVYKTI® in April 2024 for patients who have received at least one prior line of therapy and are refractory to lenalidomide.

In summary, the outcomes from the CARTITUDE-2 and CARTITUDE-4 studies reinforce the therapeutic potential of CARVYKTI® in providing deep and durable responses in multiple myeloma patients, both in early treatment settings and high-risk populations. These findings mark a pivotal advancement in the treatment of this incurable blood cancer, offering hope for better clinical outcomes.