Last week the New England Journal of Medicine published results from the Phase I Celgene bb2121 CAR T clinical trial.
In the Phase I study, 33 patients with relapsed or refractory myeloma were giving bb2121 as a single infusion of the CAR T product at different doses in the dose escalation phase (50×106, 150×106, 450×106, or 800×106 ). Two of of those doses (150×106 to 450×106) were used in the expansion phase. Patients who participated had received at least three prior lines of treatment and their myeloma had become resistant to both a proteasome inhibitor and an immunomodulator. As in all phase I studies, the goal is to assess safety.
The following data was gathered up until 6.2 months after the last patient’s infusion date:
- Most common grade 3 or higher side effects included: neutropenia (85%), leukopenia (58%), anemia (45%) and thrombocytopenia (45%).
- Grade 1 or 2 cytokine release syndrome was found in 70% of patients. Grade 3 CRS was found in 6% of patients.
- Grade 1 or 2 neurologic toxicity was found in 39% of patients. One patient had a reversible grade 4 neurologic toxic effect.
- The objective response rate was 85%. Fifteen patients (45%) had complete responses and six of these 15 have relapsed.
- Sixteen patients who had a partial response or better were tested for minimal residual disease (MRD) and had MRD negative status.
- The median progression-free survival was 11.8 months.
- The CAR T cells persisted up to 1 year after the infusion.
This graph shows each patient, the dose they received and how they have responded over a period of up to 23 months. The patients in this study were heavily pretreated. While median numbers are important, we believe that future work with CAR T cells in multiple myeloma will better identify patients who will respond well and maintain responses to this type of treatment. These are the first and most comprehensive data on CAR T in multiple myeloma to date.
According to principal investigator Noopur Raje, MD of Massachusetts General Hospital:
“The adverse events noted in our study were very manageable, and we saw low rates of cytokine release syndrome and neurotoxicity… manageable to the extent that we are now thinking [forward to] outpatient settings. Response rates were high, but we did not see a plateauing of responses in very late-stage multiple myeloma.”