A recent study conducted by Chinese researchers has shown promising results in the treatment of patients with relapsed or refractory hematologic cancers. The innovative approach combines sequential CD7 chimeric antigen receptor (CAR) T-cell therapy with haploidentical hematopoietic stem-cell transplantation (HSCT) and does not involve graft-versus-host disease (GVHD) prophylaxis. The findings suggest that this strategy could be a feasible option for patients who are not eligible for conventional allogeneic HSCT.
In the case series conducted by He Huang, MD, PhD, and colleagues from Zhejiang University School of Medicine, all 10 patients who underwent CAR T-cell therapy achieved complete remission. Nine of these patients had minimal residual disease (MRD)-negative incomplete hematologic recovery, while one had MRD-positive incomplete hematologic recovery. Subsequently, nine patients underwent haploidentical HSCT within a month. With a median follow-up of 15.1 months, six patients remained in MRD-negative complete remission, two experienced a relapse of CD7-negative leukemia, and one patient died of septic shock. The estimated 1-year overall survival rate was 68%, and the estimated 1-year disease-free survival rate was 54%.
The use of allogeneic CD7 CAR T-cell therapy as a bridge to HSCT holds promise in creating a favorable environment for successful engraftment of hematopoietic stem and progenitor cells, while maintaining GVHD control and the persistence of CAR T cells. This novel approach paves the way for future exploration in the treatment of hematologic cancers, especially for patients with a poor prognosis.
Didier Blaise, MD, from Aix-Marseille University, highlighted the importance of further studies to validate the efficacy of this “all-in-one” strategy in larger cohorts of patients. The potential application of this approach as a first-line treatment for newly diagnosed CD7-positive acute myeloid leukemia (AML) and the feasibility of using dual CAR T-cell constructs for CD7-negative leukemia raise hopes for advancing treatment paradigms in this challenging realm of cancer therapy.
The rationale behind the all-in-one strategy lies in the expression of CD7 in a significant proportion of AML cases. By leveraging CAR T-cell therapy to prepare for HSCT, the risk of relapse can be minimized, and long-term tumor elimination can be maintained. The toxic effects associated with conventional GVHD prophylaxis agents can be circumvented, providing a more tailored and potentially safer treatment option for patients with hematologic cancers.
The study cohort consisted of 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. The patients were heavily pretreated, with a median of 9.5 previous courses of therapy. Median patient age was 56.5 years, and 60% of the patients were women. Bone marrow involvement was observed in all patients, with a median blast percentage of 36%. The majority of patients had AML, while others had T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma.
Several patients experienced cytokine release syndrome (CRS) after treatment, albeit all cases were mild to moderate. Grade 2 graft-versus-host disease (GVHD) was reported in four patients, while no cases of chronic GVHD were observed. Two patients succumbed to septic shock following infections, highlighting the importance of close monitoring and effective management of potential complications in patients undergoing this novel treatment approach.
The combination of sequential CD7 CAR T-cell therapy and haploidentical HSCT without GVHD prophylaxis represents a promising strategy for patients with relapsed or refractory hematologic cancers. While further research is warranted to validate the findings and optimize treatment protocols, this innovative approach opens new avenues for improving outcomes in this challenging patient population.