“All-in-One” Therapy for Relapsed Acute Leukemia

While chimeric antigen receptor (CAR) T-cell therapies are now a standard treatment for relapsed or refractory B-cell malignancies, their application in myeloid and T-cell neoplasms has lagged behind, in part due to effects on normal hematopoiesis. Now, investigators report a novel approach of induction therapy with an anti-CD7 CAR T-cell product followed by hematopoietic reconstitution via haploidentical allogeneic hematopoietic stem-cell transplantation (alloHSCT).

Seventeen patients with relapsed CD7-positive acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma received a haploidentical donor-derived anti-CD7 CAR-T infusion. Of those, 10 patients achieved complete remission with incomplete hematologic recovery and severe marrow hypocellularity, plus detectable circulating CD7 CAR T cells, and were eligible for haploidentical alloHSCT using the original T-cell donor. Conditioning chemotherapy (fludarabine, cyclophosphamide, and etoposide) was given prior to CAR T-cell infusion. No pre- or post-alloHSCT graft-versus-host disease (GVHD) prophylaxis was administered.

One patient died of infection 13 days after HSCT, eight had successful engraftment, and one had autologous blood count recovery. Another patient later died from infection, and two from CD7-negative leukemia relapse. At a median follow-up of 15.1 months, six patients remained in ongoing remission. Estimated 1-year disease-free survival was 54%. No cytokine release syndrome occurred; grade 1–2 acute GVHD was observed in three patients, with no chronic GVHD.