A phase 1 trial of GC012F demonstrated an overall response rate of 100% in high-risk, transplant-eligible patients with newly diagnosed multiple myeloma.
Outcomes with first-line therapy in patients with high-risk (HR) newly diagnosed multiple myeloma (NDMM) are generally poor, even in patients eligible for transplant. Chimeric antigen receptor (CAR) T-cell therapies are novel agents currently being developed in MM, and investigators seek to identify efficacious and tolerable CAR T-cell therapies in this patient population. GC012F is an autologous B-cell maturation antigen (BCMA) and CD19 dual-targeting CAR T-cell therapy that showed deep and durable responses in a phase 1, single-arm study of relapsed/refractory MM, heavily pretreated patients. These results were the basis for a single-arm, phase 1 study of GC012F in the frontline for transplant-eligible HR NDMM patients, the results of which were presented by Juan Du at the 2022 American Society of Hematology meeting.
Patients received a single GC012F infusion at 3 dose levels. High-risk features included International Staging System stage II or III, del17p, t(4;14), t(14;16), 1q21amp ≥4 copies, extramedullary disease, IgD or IgE subtype, lactate dehydrogenase (LDH) greater than the upper limit of normal, or any high-risk definition of mSMART3.0. A total of 16 patients who received GC012F were included in the analysis; 15 patients received 2 cycles of induction with bortezomib, lenalidomide, and dexamethasone. After a median follow-up of 8 months, the overall response rate (ORR) was 100%, and all patients achieved a very good partial response or better. All minimal residual disease (MRD)-evaluable patients achieved MRD negativity, and there was no difference observed across dose levels. Cytokine release syndrome occurred in 25% of patients. All were grade 1 or 2 with a median onset of 6 days and median duration of 2 days. No patients experienced immune effector cell–associated neurotoxicity syndrome. The most common hematologic treatment-emergent adverse events (TEAEs) were neutropenia, lymphopenia, and leukopenia, all of which occurred in 88% of patients across all grades. The most common grade 3 or 4 hematologic TEAEs were neutropenia (44%), lymphopenia (81%), and leukopenia (50%). Non-hematologic TEAEs included LDH increase and hypoalbuminemia, all of which were low grade.
This study showed promising efficacy with GC012F in transplant-eligible HR NDMM patients, with an ORR and MRD negativity of 100% and a tolerable safety profile. These results warrant further follow-up and larger studies in these patients.
- Du J, Fu W, Lu J, et al. Phase I open-label single-arm study of BCMA/CD19 dual-targeting FasTCAR-T cells (GC012F) as first-line therapy for transplant-eligible newly diagnosed high-risk multiple myeloma. Presented at: 2022 American Hematology Society Annual Meeting; December 10-13; New Orleans, LA. Abstract 366.