Early, deep, and durable responses following a single infusion of CB-011 in high-risk relapsed/refractory multiple myeloma patients: A case series from the CaMMouflage trial
Introduction: CB-011 is an allogeneic anti-BCMA CAR-T cell therapy with immune cloaking manufactured from healthy donor T cells. It features 4 genome edits made with the CRISPR-Cas12a chRDNA genome-editing technology: (1) insertion of a BCMA-specific CAR, (2) TRAC gene knockout (KO) to reduce risk of graft-versus-host disease (GvHD), (3) KO of the B2M gene to reduce T cell-mediated rejection, and (4) B2M-HLA-E fusion insertion to blunt natural killer (NK) cell-mediated rejection. CB-011 is being evaluated in the CaMMouflage phase 1 trial (NCT05722418) for patients (pts) with r/r MM. Here we present a case series of 3 patients with high-risk, heavily pretreated r/r MM who each have an ongoing complete response (CR) or stringent CR (sCR) more than 18 months following infusion without subsequent therapy.
Materials and Methods/Case Presentation/Objective:
Methods: These 3 BCMA-naive patients received ≥3 prior lines of therapy (including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody). All patients received the recommended dose for expansion (RDE) regimen: lymphodepletion for 3 days of 500 mg/m2 cyclophosphamide with 30 mg/m2 fludarabine followed by a single infusion of 450 million CB-011 CAR-T cells.
Patient Case 1: A 53-year-old male was diagnosed with MM in August 2021. At the time of enrollment, he had extramedullary disease (EMD), high-risk cytogenetics (t(4;14); FGFR3 and MMSET), and lytic bone lesions. This patient received 3 prior lines of therapy. The best response observed was a very good partial response (VGPR) after treatment with daratumumab, pomalidomide, and dexamethasone (DPd) in the 3rd-line setting.
Patient Case 2: An 80-year-old female was diagnosed with MM in November 2021. She had high-risk cytogenetics (del13q + duplication or amplification of 1q) and lytic bone lesions. This patient received 4 prior lines of therapy. The best response was CR after treatment with daratumumab, carfilzomib, and dexamethasone (DKd) in the 3rd-line setting.
Patient Case 3: A 70-year-old female was diagnosed with MM in August 2019. She had EMD and high-risk cytogenetics (del13q + duplication or amplification of 1q). This patient received 4 prior lines of therapy. The best response was sCR after treatment with daratumumab, talquetamab, and lenalidomide in the 4th-line setting.
Results/Description/Main Outcome Measure(s):
Results: Following a single infusion of CB-011, Patient Case 1 achieved a sCR and MRD negativity at Day 28 and remains in ongoing sCR beyond 18 months; no AESIs occurred. Patient Case 2 achieved MRD negativity and a VGPR at Day 28, with the response deepening to a CR at 12 months, which remains ongoing beyond 18 months; Grade 1 CRS occurred and resolved. Patient Case 3 achieved MRD negativity and a VGPR at Day 28, with the response deepening to a sCR at 3 months, which remains ongoing beyond 18 months; no AESIs occurred.
Conclusion(s).:
Conclusions: In 3 high-risk, heavily pretreated patients with r/r MM, CB-011 achieved early, deep, and durable responses with a manageable safety profile. Enrollment of BCMA-naive and prior BCMA-exposed r/r MM patients is ongoing in the dose expansion portion of the CaMMouflage trial.
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