Factors Affecting EFS After CAR-T Therapy Identified in Certain Patients With B-ALL

Baseline platelet count, lactate dehydrogenase, and lymphodepletion regimen are factors associated with event-free survival (EFS) outcomes in patients with B-cell acute lymphoblastic leukemia (B-ALL) who achieve MRD-negative complete remission (CR) after CD19 CAR T-cell therapy, according to a study published in Blood (2019;133[15]:1652-1663).

Autologous T-cells expressing CD19-specific CARs have led to impressive MRD-negative  CR rates in patients with relapsed or refractory B-ALL, explained Kevin A. Hay, MD, FRCPC, MSc, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues.

“However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated,” they added.

Dr Hay and colleagues studied patients with relapsed or refractory B-ALL who were already enrolled in a phase 1/2 trial at the Fred Hutchinson Cancer Research Center, the purpose which was to evaluate the use of lymphodepletion chemotherapy followed by CD19 CAR-T therapy in this setting.

Of 53 patients who received CD19 CAR-T therapy, 45 achieved MRD-negative CR by high-resolution flow cytometry and were deemed evaluable.

At a median follow-up of 30.9 months, the median EFS was 7.6 months among patients who achieved MRD-negative CR by flow cytometry versus 0.8 months among those who did not (P <.0001). The median OS was 20.0 months versus 5 months, respectively (P = .014).

“In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by IGH deep sequencing was associated with better EFS (P = .034),” Dr Hay and colleagues noted.

In addition, stepwise multivariable modeling showed that lower prelymphodepletion lactate dehydrogenase concentration (hazard ratio [HR], 1.38 per 100 U/L increment increase), higher prelymphodepletion platelet count (HR, 0.74 per 50 000/μL increment increase), incorporation of fludarabine into the lymphodepletion regimen (HR, 0.25), and allogeneic hematopoietic cell transplantation (HCT) after CAR-T therapy (HR, 0.39) were associated with better EFS in this patient population.

“These data allow identification of patients at higher risk of relapse after CAR T-cell immunotherapy who might benefit from consolidation strategies such as allogeneic HCT,” the investigators concluded.—Janelle Bradley