BCMA AND CD19 CAR T CELL THERAPY

The FDA added a boxed warning for T cell malignancies in patients receiving BCMA- or CD19-directed autologous CAR T cell immunotherapies after reports post treatment, T-cell malignancies. Patients now must be monitored for secondary malignancies, potentially requiring ongoing vigilance. This will affect market-leading myeloma products including Abecma, Carvykti, and Breyanzi.

MULTIPLE MYELOMA

The FDA approved Bristol Myers Squibb and 2seventybio's Abecma (idecabtagene vicleucel) for triple-classexposed relapsed or refractory (R/R) multiple myeloma after two prior lines of therapy. Abecma demonstrated a51% reduction in the risk of disease progression or death and has a well-established safety profile. These results expand Abecma's availability earlier in treatment sequencing with meaningful treatment-free intervals.

MULTIPLE MYELOMA

The European Commission approved CARVYKTI(ciltacabtagene autoleucel; cilta-cel) for relapsed and refractory (R/R) multiple myeloma patients, achieving a74% reduction in disease progression or death risk in previous lines of therapy. The approval is based on the Phase 3 CARTITUDE-4 study results, showing higher response rates and overall survival with cilta-celcompared to standard therapies. Results from the study demonstrated a 76% progression-free survival rate at12 months and an 85% overall response rate withcilta-cel.

MULTIPLE MYELOMA

Regeneron announced positive data from the Phase 1/2LINKER-MM1 trial of linvoseltamab showing a 71%objective response rate in heavily pre-treated multiple myeloma patients, accompanied by a deepening of response over time. In particular, this promises a long term treatment not currently available, particularly effective with high-risk and high-disease burdenpopulations. Phase 3 trials are ongoing, withlinvoseltamab currently under FDA review for priority approval with a target action date of August 22, 2024.

MULTIPLE MYELOMA

In a study from the Mayo Clinic on outcomes of therapies in multiple myeloma patients refractory tolenalidomide after receiving it as a first line therapy, it was determined that the definition of refractoriness is not dependent on dose. The study showed that outcomes did not differ between standard and low dose refractory groups for second line therapy(p=0.95), and the PFS for lenalidomide retreatmentwas inferior in both groups compared to nonrefractory patients (p<0.001). Given standard vs low dose refractoriness did not impact clinical outcomes,highlighting lenalidomide resistance independence of dose.

MULTIPLE MYELOMA

The FDA held an Oncologic Drugs Advisory Committee (ODAC)meeting on April 12th, 2024 where it acknowledged the value of minimal residual disease (MRD) as an endpoint for accelerated approval in multiple myeloma. The FDA noted with a strong association between MRD negativity and progression-free survival and overall survival. In a meta-analysis, 12-month MRD negativity significantly correlated with progression-free survival and overall survival, supporting MRD as a predictivebiomarker. Despite the resolution, the FDA noted limitations in trial design, assay standardization, and populationheterogeneity which may improve in future studies.