BB2121 CAR T Results Described in New England Journal of Medicine

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.”