August 2017 VOL 8, NO 8

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2017 Annual Meeting of the American Association for Cancer Research

Transplant Questionable After CAR T-Cell Treatment in Relapsed B-ALL

Transplant Questionable After CAR T-Cell Treatment in Relapsed B-ALLCAR T-cell therapy achieved excellent responses in an updated report on a series of 50 patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) treated with CAR T-cells at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City. In a retrospective analysis, patients who had minimal disease burden at the time of CAR T-cell infusion had improved durability of response and longer survival compared with those who had morphologic disease. Patients with minimal disease burden also had fewer serious side effects, a lower incidence of cytokine release syndrome (CRS), and a lower rate of neurotoxicity.

Durable responses and survivals were observed in a proportion of relapsed B-ALL patients who did not undergo subsequent allogeneic stem cell transplantation after CAR T-cell therapy. These findings suggest that some patients can be treated with CAR T-cells and no further therapy. Results were presented at the 2017 Annual Meeting of AACR.

“The benefit of transplant after CAR T-cell infusion is uncertain. These findings raise the question of whether using CAR T-cells at the time of minimal residual disease [MRD] after first-line chemotherapy can achieve CAR T-cell–mediated remissions and maximize survival, potentially sparing high-risk patients from transplant, rather than waiting until they relapse morphologically and then trying CAR T-cell therapy when it is less likely to achieve a durable long-term remission,” said lead author Jae H. Park, MD, assistant attending physician at MSKCC.

In the pre-CAR T-cell era, in adults with relapsed or refractory B-ALL, the expected 5-year survival rate was approximately 8%. The CAR T-cell was developed in an attempt to extend survival in these patients. Several groups of investigators use different platforms and different vectors for their version of CAR T-cells. The group at MSKCC is using a CD19-28z platform.

The phase 1 study included 50 patients with relapsed CD19-positive B-ALL treated with CAR T-cells using autologous or patient-derived T cells (fresh or frozen). Patients were aged 18 years or older.

Bone marrow biopsies were performed at 4 weeks after CAR T-cell infusion to document response. Patients were stratified into morphologic disease (≥5% blasts in bone marrow) or MRD (<5% blasts in bone marrow); those with MRD were treated with higher doses of CAR T-cells.

Complete response rates were 95% in those with MRD and 77% in those with morphologic disease.

At a median of 18 months of follow-up, median event-free survival and overall survival were not reached for patients in the MRD cohort and were 6.3 months and 17 months, respectively, for the morphologic disease cohort (P = .0005 for the difference in event-free survival between disease-burden groups and P = .0189 for the difference in overall survival between disease-burden groups).

Although the numbers are small in this study, post-CAR T-cell transplantation did not affect survival. Disease burden was the only factor that affected survival.

Disease burden also impacted adverse events. Severe CRS was reported in 42% of those with morphologic disease and only 5% of the MRD cohort. Grade 3/4 neurotoxicity was reported in 58% and 15%, respectively. Grade 5 toxicity occurred in 13% and 0%, respectively. No grade 5 neurotoxicity was observed.

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