Study of CAR-T Cell Therapy for multiple myeloma announced at ASH 2017

Celgene Corporation and bluebird bio, Inc. announced that updated results from the ongoing CRB-401 Phase 1 clinical study of bb 2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma will be presented in an oral presentation at the American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia. The objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase II dose. Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: Updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy (Abstract #740) Presenter: James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland Date: Monday, December 11, 3:00 pm.

Patients on study were heavily pre-treated, with a median of 7 prior therapies (range: 3 - 14):

• 100% previously treated with lenalidomide and bortezomib

• 91% previously treated with pomalidomide and carfilzomib.

• 71% previously treated with daratumumab. 

• 29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab).

• All patients had at least one prior autologous stem cell transplant (ASCT).

As of the October 2, 2017 data cut-off, 21 patients had been enrolled and dosed in the dose-escalation phase of the study, in four dose cohorts: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells. This multi-center study has enrolled patients at nine sites in the U.S. with central manufacturing performed at Celgene.

Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient's own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Results in the active dose cohorts (150 x 106, 450 x 106 and 800 x 106 CAR+ T cells; N=18) were:

• Median follow-up was 40 weeks (range: 6.6-69)

• 17/18 (94%) patients achieved an objective response

• 16/18 (89%) patients achieved at least a very good partial response (VGPR)

• 10/18 (56%) patients achieved a complete response (CR, N = 7), or unconfirmed complete response (N = 3)

• 9 of 10 patients who were evaluable for MRD status were found to be MRD-negative

• Median PFS has not been reached in the active dose cohorts. The PFS at 6 months and 9 months was 81% and 71%, respectively

• Three patients in the dose-escalation who responded to therapy subsequently experienced disease progression .

In the dose-escalation phase, 15/21 (71%) of patients had cytokine release syndrome (CRS), mostly Grade 1 & 2, with 2 patients experiencing Grade 3 CRS (9%). Four patients received tocilizumab, 1 (Grade 2 CRS) received steroids and in each case the CRS resolved within 24 hours. The most common treatment-emergent Grade 3-4 AEs in 21 infused patients were cytopenias commonly associated with lymphodepleting chemotherapy including neutropenia (86%), anemia (57%) and thrombocytopenia (43%). There were two deaths in the active cohorts at 22 and 69 weeks following infusion, respectively. The first was due to cardiac arrest and the second was due to myelodysplastic syndrome; both subjects were in a myeloma CR at their last study assessment prior to death. Based on the findings during dose escalation, a dose expansion phase of 12 subjects has started testing doses between 150-450 x 106 CAR+ T cells. In the dose expansion phase, one patient treated at the 450 x 106 CAR+ T cells dose experienced Grade 4 neurotoxicity including focal cerebral edema and subarachnoid hemorrhage. This patient had a high tumor burden, and a history of subarachnoid hemorrhage. The event was successfully managed, and the patient remains in the response group. No other Grade 3/4 neurotoxicity was observed in the escalation or expansion cohort.