CAR-T Plus Stem-Cell Transplant Promising for CD7+ Blood Cancers

A strategy of sequential CD7 chimeric antigen receptor (CAR) T-cell therapy and haploidentical hematopoietic stem-cell transplantation (HSCT), without graft-versus-host disease (GVHD) prophylaxis, is a feasible approach for patients with relapsed or refractory hematologic cancers who are ineligible for conventional allogeneic HSCT, Chinese researchers said.

After CAR T-cell therapy, all 10 patients in their case series had complete remission, including nine with minimal residual disease (MRD)-negative incomplete hematologic recovery and one with MRD-positive incomplete hematologic recovery, reported He Huang, MD, PhD, of Zhejiang University School of Medicine in Hangzhou, China, and colleagues.

Nine of the patients then underwent haploidentical HSCT within 1 month, and with a median follow-up of 15.1 months, six patients remained in MRD-negative complete remission, two patients had a relapse of CD7-negative leukemia, and one died of septic shock, they noted in the New England Journal of Medicine.

The estimated 1-year overall survival rate was 68%, and the estimated 1-year disease-free survival rate was 54%.

"This innovative procedure exploited allogeneic CD7 CAR T-cell therapy (including lymphodepletion before CAR T-cell infusion) to create a specific condition for successful allogeneic HSPC [hematopoietic stem and progenitor cell] engraftment, GVHD control, and concomitant persistence of CAR T cells, thus opening a new strategic approach for allogeneic HSCT," Huang and team wrote.

In an editorial accompanying the study, Didier Blaise, MD, of Aix-Marseille University in France, noted that the results of the study -- while preliminary -- were promising, and further study of this "all-in-one" approach in larger numbers of patients is ongoing, with results that could open up areas of exploration.

For example, he pointed to the strategy being considered in the first line for patients with newly diagnosed CD7-positive acute myeloid leukemia (AML) who are unable to undergo intensive induction therapy. He also contemplated the possibility of dual CAR T-cell constructs targeting both CD7 and another antigen for CD7-negative leukemia.

If these scenarios are possible, "the described strategy offers hope for advancing treatment paradigms in this difficult realm of AML with a poor prognosis," Blaise wrote.

In explaining the rationale behind the use of this all-in-one strategy, Huang and colleagues noted that CD7 is expressed in about 30% of AML cases. CAR T-cell therapy as a bridge to allogeneic HSCT has the potential to maintain long-term tumor elimination and reduce the risk of relapse, they suggested. "However, pre-HSCT myeloablation and GVHD prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects."

They also pointed out that unfit patients are often ineligible for allogeneic HSCT.

The 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma in this case series were enrolled in one of two prospective clinical studies from November 2021 through September 2023.

Nine patients were enrolled in a clinical study of donor-derived CD7 CAR T cells, and one was enrolled in a compassionate-use program that provided access to universal CD7 CAR T cells after the end of the clinical study. They were considered eligible for the all-in-one strategy if they had complete remission with incomplete hematologic recovery and severe bone marrow hypocellularity or pancytopenia after CD7 CAR T-cell therapy, had detectable CD7 CAR T cells, and had no history of allogeneic HSCT.

Of those 10 patients, seven had AML, two had T-cell acute lymphoblastic leukemia, and one had T-cell lymphoblastic lymphoma.

Median patient age at enrollment was 56.5 years, 60% were women, and all had been heavily pretreated, with a median of 9.5 previous courses of therapy.

Bone marrow involvement was identified in all patients, with a median percentage of blasts of 36%. Two patients had extramedullary disease. The median percentage of CD7 expression on blast cells was 93%.

The median time from CAR T-cell infusion to HSPC infusion was 19 days.

One patient had pancytopenia for 3 months after CAR T-cell infusion, complicated with candida sepsis followed by Enterococcus faecalis infection. A salvage haploidentical HSPC infusion was performed on the patient, which relieved the pancytopenia. The other nine patients proceeded to undergo haploidentical HSCT within 1 month after CAR T-cell infusion.

Cytokine release syndrome (CRS) occurred in nine patients -- all grade 1 or 2 -- with a median time to onset of 1 day, and a median duration of 9.5 days. All episodes of CRS were successfully controlled. Four patients had cases of grade 2 GVHD. There were no cases of chronic GVHD.

One patient had a multidrug-resistant bloodstream infection at 3.3 months followed by intracranial infection, and died of septic shock at 3.7 months. Another patient died 13 days after HSCT of septic shock due to Staphylococcus haemolyticus infection and encephalitis due to human herpesvirus 6 infection. Infections in other patients were successfully treated with antibiotics.

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