CD19-specific chimeric antigen receptor (CAR) T-cell therapy is more likely to be effective when given immediately after front-line therapy rather than after relapse in certain patients with B-cell acute lymphoblastic leukemia (ALL), according to research presented at the American Association for Cancer Research (April 1-5, 2017; abstract CT078).
CAR T-cells have shown high initial responses in patients with relapsed B-cell ALL. However, limited data exist regarding clinical characteristics and their associations with durability of response.
Jae H Park, MD, Memorial Sloan Kettering Cancer Center (New York, NY), and colleagues, conducted a study to analyze pre-treatment B-cell ALL burden and post-CAR T-cell allogeneic transplant on long-term clinical outcome. The phase I study was comprised of 51 adults with relapsed ALL who were infused with autologous T-cells expressing the 19-28z CAR. Patients were grouped into 2 cohorts based on disease burden upon T-cell infusion: minimal residual disease (<5% blast cells in bone marrow, n = 20 patients) and morphologic disease (≥5% blast cells, n = 31 patients). Median follow-up duration was 18 months.
Results of the analysis showed no significant difference in complete response rates between the cohorts (95% vs 77%, respectively). However, after median follow-up, most patients in the minimal residual disease cohort prior to infusion were still disease-free (P = .0005), whereas those in the morphologic disease cohort had an event-free survival of 6.3 months and an overall survival of 17 months (P = .0189).
Additionally, researchers found that hematopoietic stem cell transplant after CAR T-cell therapy did not improve long-term survival for patients in either cohort, suggesting that patients with minimal residual disease burden prior to infusion should receive CAR T-cell therapy immediately after first-line treatment, rather than waiting for relapse to occur.
"Despite comparable initial complete response rates between the two cohorts, durability of 19-28z CAR T-cell mediated remissions and survival in adult patients with relapsed B-cell ALL positively correlated to a low disease burden and do not appear to be enhanced by allogeneic transplant. Our findings strongly support the early incorporation of CD19 CAR-T therapy before morphologic relapse in B-cell ALL," said Dr Park.
Findings from this retrospective analysis will need to be validated in a prospective setting, researchers acknowledged. – Zachary Bessette