Allogeneic anti-BCMA CAR-T therapy granted FDA RMAT designation
Currently, all approved CAR-T therapies, including those for treating patients with multiple myeloma (MM), are autologous. An allogeneic anti-BCMA CAR-T therapy for MM — CB-011 — has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the US FDA. CB-011 yielded deep and durable responses in high-risk patients with heavily pre-treated relapsed/refractory MM (RRMM) in the dose escalation portion of the ongoing phase 1 CaMMouflage trial.

Reduced BCMA expression is common at relapse after BCMA CAR-T therapy
In an analysis of BCMA expression over time among 76 patients who received anti-BCMA CAR-T therapy, BCMA expression decreased by ≥25% at relapse, compared to baseline, in half. Notably, BCMA expression in plasma cells by flow cytometry, but not immunohistochemistry, correlated with clinical outcomes, according to the report in Blood Cancer Journal.

Bispecific antibodies are efficacious and safe in the setting of renal impairment
According to a systematic review published in the American Journal of Hematology, which included over 1100 patients from clinical trials and real-world studies, response rates to bispecific antibody therapies in patients with renal impairment were comparable to those with normal kidney function, without increased risk of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.

Review explores genomic underpinnings of MM evolution
The complex pathogenesis of MM is characterized by genomic heterogeneity and a lack of universal driver mutations. A review published in Blood explores how environmental exposure-driven genetic changes, genetic predispositions, and immune surveillance impinge on myeloma evolution, from precursor conditions to active disease.

Anti-CD38 monoclonal antibody-based quadruplets outperform triplets
In a systematic review and meta-analysis of over 2000 patients across six randomized clinical trials, anti-CD38 monoclonal antibody-based quadruplet regimens yielded longer progression-free and overall survival, as well as higher minimal residual disease-negativity rates, compared with triplet regimens, in non-frail transplant-ineligible patients with MM. These findings were reported in the International Journal of Hematology.

BCMA/CD19 dual CAR-T therapy shows preliminary efficacy in older patients
While older and/or frail patients with RRMM are often underrepresented in CAR-T therapy trials, retrospective analyses support the efficacy of BCMA CAR-T therapies in this vulnerable subset. AZD0120, a dual CAR-T targeting BCMA and CD19 manufactured using the Fast CAR® platform, yielded stringent complete responses in four frail and four non-frail patients with RRMM aged ≥70 years. These findings from a phase 1 study were reported in Blood Advances.