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CAR T-cell therapy induced high complete response rate in advanced B-ALL
Treatment with genetically engineered T cells appeared highly effective in a cohort of patients with advanced B-cell acute lymphoblastic leukemia, according to study results.
Researchers reported an 88% overall complete response rate, and the therapy also induced complete remissions in more than three-quarters of patients who had detectable disease before treatment.
Michel Sadelain
“These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies,” researcher Michel Sadelain, MD, PhD, director of the Center for Cell Engineering at Memorial Sloan-Kettering Cancer Center, said in a press release. “Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”
Most patients with adult B-cell acute lymphoblastic leukemia (B-ALL) relapse, and patients with relapsed B-ALL have few treatment options. Only 30% respond to salvage chemotherapy, and unless bone marrow transplant is successful, long-term survival is unlikely. Median survival among these patients is less than 6 months, according to background information provided by researchers.
The current study included 16 patients (median age, 50 years) with relapsed or refractory B-ALL. The cohort included four patients with Philadelphia chromosome-positive disease and four patients who relapsed after allogeneic stem cell transplant (allo-SCT).
All patients underwent leukapheresis and salvage chemotherapy of their physician’s choice, followed by cyclophosphamide-conditioning chemotherapy.
They then underwent treatment with genetically modified versions of their own immune cells. The autologous T cells expressed the 19-28z chimeric antigen receptor (CAR) and were designed to target cancer cells that contained the CD19 protein.
A dose of 3 x 106 CAR T cells/kg was used for 15 of the 16 patients.
Fourteen patients (88%) demonstrated complete response, a markedly higher rate than that anticipated with salvage chemotherapy alone, Sadelain and colleagues wrote. Seventy-eight percent of patients who had detectable disease prior to treatment demonstrated a complete response.
Researchers successfully transitioned seven patients (44% of the overall cohort) to allo-SCT, a rate nearly ninefold higher than that historically reported among adults with relapsed or refractory B-ALL.
“Thus, 19-28z CAR T-cell therapy may represent an effective ‘bridge’ to allo-SCT,” Sadelain and colleagues wrote. “Because most of our patients underwent allo-SCT in the setting of a complete molecular remission, we hypothesize that transplants performed under these optimal conditions will markedly, if not completely, reduce the historical 30% disease relapse rate of B-ALL patients after allo-SCT.”
To date, none of the seven patients who underwent allo-SCT after CAR T-cell therapy relapsed (follow-up range, 2 to 24 months), although two died while in complete molecular remission from complications related to stem cell transplant.
Based on their analysis of serum cytokine levels and other patient data during the first 21 days after T-cell infusion, researchers said they established laboratory and clinical criteria to diagnose CAR T-cell–related cytokine release syndrome (CRS). Those criteria may better identify patients who will need corticosteroid or interleukin-6 receptor blockade therapy for severe CRS. The investigators also determined that serum C-reactive protein serves as a reliable indicator for CRS severity.
“Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T-cell therapy,” the researchers concluded.
Disclosure: Sadelain and two other researchers report financial relationships with Juno Therapeutics.