Sequential CD7 CAR T-cell therapy and allogeneic stem cell transplantation without GVHD prophylaxis

Patients with relapsed or refractory hematologic cancers have a poor prognosis. CAR T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and GCHD prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. A prospective study in China evaluated sequential CD7 CAR T-cell therapy and haploidentical HSCT without myeloablation and GVHD prophylaxis in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy, all patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After HSCT, one patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and one patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range 3.1-24.0) after CAR T-cell therapy. Six patients remained in MRD-negative complete remission, two had a relapse of CD7-negative leukemia, and one died of septic shock at 3.7 months. The estimated 1-year overall survival and disease-free survival were 68% (95% CI 43-100) and 54% (29-100), respectively. The authors conclude that sequential CD7 CAR T-cell therapy and haploidentical HSCT was safe and effective, resulting in remission with serious but reversible adverse events.