Legend Biotech Corporation announced results for the first time from the Phase 2 CARTITUDE-2 Cohort D study in multiple myeloma patients. Results showed patients with less than a complete response (CR) after front-line autologous stem cell transplant (ASCT) experienced deep and durable responses following a single infusion of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) with or without lenalidomide maintenance. These data were presented as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7505) and will also be shared as an encore oral presentation at the 2024 European Hematology Association (EHA) Congress (Abstract #S205).

CARVYKTI is the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with relapsed/refractory multiple myeloma as early as after first relapse. At a median follow-up of 22 months, patients treated with CARVYKTI (n=17) demonstrated a 94% (n=16/17) overall response rate (ORR) with all 16 patients achieving a CR or better. Of the 15 minimal residual disease (MRD)-evaluable patients, 80% achieved MRD negativity at the 10?5 threshold.

The median duration of response (mDOR) was not reached (NR) and the median time to first response was one month. Safety signals were consistent with the known safety profile of CARVYKTI. All patients had grade 3 or 4 treatment emergent adverse events (TEAEs) including neutropenia (94%), lymphopenia (65%), thrombocytopenia (47%), leukopenia (41%), infections (71%), or CRS (82%; median onset of 8 days).

One patient had a secondary malignancy of grade 3 myelodysplastic syndromes (MDS). No cases of movement and neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism were observed. CARTITUDE-4 is a Phase 3 study evaluating CARVYKTI versus two standard of care therapies of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD).

Results from this subgroup analysis showed CARVYKTI significantly improved PFS for patients with functional high-risk (FHR) multiple myeloma, defined as disease progression within 18 months following ASCT or following initiation of first-line treatment. The subgroup analysis included patients (n=136) who received one prior line of therapy, including a PI and an IMiD and were lenalidomide-refractory, including patients (n=79) who had FHR multiple myeloma. Patients were randomized to CARVYKTI (n=68) or standard therapies (n=68), including those with FHR multiple myeloma (CARVYKTI, n=40; standard therapies, n=39).2 Median PFS was NR among patients who received CARVYKTI compared to 17 months (95% Confidence Interval,11-NE) for the control arm as a second-line treatment (HR=0.35 [95% CI, 0.2-0.7; P=0.0007]), including those who had FHR multiple myeloma (CARVYKTI, NR [95% CI,18-NE]; standard therapies, 12 months [95% CI, 8-NE]), (HR=0.27 [95% CI, 0.1-0.6; P=0.0006]).

Patients treated with CARVYKTI who had FHR multiple myeloma compared to those treated with standard therapies had consistently higher rates of overall responses (88%; 80%), CR or better (68%; 39%), MRD negativity (65%; 10%), and longer mDOR (NR [16-NE]; 16 [8-NE]). The safety profile in this subgroup analysis was consistent with the known safety profile of cilta-cel. The proportion of patients with grade 3 or higher TEAEs was comparable among patients who received CARVYKTI versus standard therapies as second-line treatment (96%, 96%), including those with FHR multiple myeloma (100%, 97%).

Overall, 11 patients who received CARVYKTI after one prior line of therapy and 11 patients who received standard therapies after one prior line of therapy died. Of the patients with FHR multiple myeloma, 7 patients from the CARVYKTI arm, and 9 who received standard therapies died. Of the 7 deaths in patients with one prior line of therapy and functionally high-risk multiple myeloma, did not receive CARVYKTI as study treatment, and 3 received CARVYKTI as subsequent therapy.

CARTITUDE-4: Subgroup analysis of patients with high-risk cytogenetics demonstrates favorable efficacy for CARVYKTI®vs standard therapy (Abstract #P978): CARVYKTI® demonstrated favorable efficacy outcomes ? including higher ORR, =CR rates, and MRD negativity rates and improved PFS ? vs SOC in patients with high-risk and standard-risk cytogenetics.

In patients with standard-risk cytogenetics, median PFS was not reached (NR; 95% CI, NE-NE) with CARVYKTI® vs 20.6 months (95% CI, 11.2-NE) with SOC. In patients with high-risk cytogenetics, median PFS was not reached (95% CI, 18.4?NE) with CARVYKTI® vs 10.3 months (95% CI, 7.6?12.5) with SOC. Results from the Phase 3 CARTITUDE-4 subgroup analysis demonstrate the efficacy of CARVYKTI® versus SOC in patients with high-risk-cytogenetics, supporting the role of CARVYKTI® as a potential new SOC in this patient population.

Data from the CARTITUDE-4 study supported the U.S. FDA approval of CARVYKTI® on April 5, 2024, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy (LOT), including a PI and an IMiD, and are refractory to lenalidomide.