Relapse after CAR-T liked to shorter survival among younger patients with ALL
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Younger patients who experienced disease progression after CD19-directed chimeric antigen receptor T-cell therapy had significantly shorter OS than those who did not relapse, according to results presented at TCT Meetings Digital Experience.
Results of the retrospective study also showed a lack of a standard approach to salvage therapy for patients who relapse after CAR T-cell therapy, according to Heather E. Stefanski, MD, PhD, associate professor of pediatrics in the division of blood and marrow transplant & cellular therapy at University of Minnesota School of Medicine.
“We wanted to examine how patients fared when they relapsed after CAR-T and whether they could benefit from salvage therapy,” Stefanski told Healio.
In addition to the worse survival outcomes observed among patients who relapsed, those who had CD19-negative relapses had much worse outcomes than those who had CD19-positive relapses, she added.
Stefanski and colleagues examined which, if any, salvage therapies could lead to lasting remissions among children and young adults who received tisagenlecleucel (Kymriah, Novartis) — an autologous, gene-edited, CD19-directed CAR T-cell therapy — for ALL and experienced disease relapse after treatment.
The researchers used retrospective data from the Pediatric Real World CAR Consortium, which includes 15 member institutions that provide CAR T-cell therapy in in the U.S.
The study cohort included 185 children and young adults who received commercial tisagenlecleucel for relapsed or refractory ALL.
A total of 156 patients had a response to treatment at 28 days. Of these patients, 57 (37%) experienced disease relapse and 30 died, including 24 after relapse and six without relapse.
Median follow-up was 0.64 years after disease relapse.
Stefanski and colleagues used a Cox proportional hazards model to study the association of relapse after CAR T-cell therapy and mortality. Results showed a significantly increased risk for death when relapse was evaluated as a time-dependent covariate (HR = 12.5, 95% CI, 5.24-29.8) and in a landmark analysis at day 180 after infusion (HR for relapse by day 180 = 4.75, 95% CI, 1.86-12.1).
A multivariate analysis of OS after disease relapse showed none of the salvage therapies evaluated — including hematopoietic stem cell transplant, subsequent CAR T-cell therapy, chemotherapy or monoclonal antibodies — resulted in significant improvement in survival.
However, the results showed increased risk for death among patients who received salvage chemotherapy (HR = 2.64; 95% CI, 1.14-6.13) and HSCT (HR = 1.76; 95% CI, 0.54-5.71).
Given the results of the study, the best chance for patients to avoid relapse after CAR T-cell therapy is the development of more effective CAR T cells, Stefanski said.
“None of the other salvage therapy options were routinely effective,” she said. “Developing more a more effective CAR-T therapy upfront will be in the best interest of patients.”
Another strategy may be to provide patients with higher doses of CAR T cells during initial therapy, as was indicated by results of another study her group presented at this year’s TCT Meetings Digital Experience.
The results also show a need to develop a consensus on the best approach for treating younger patients with ALL who relapse after CAR T-cell therapy, according to Stefanski.
“A more uniform approach is needed,” she said.
What that would entail is unknown at this point, Stefanski said, especially given her group’s data showing no significant survival improvement with any of the salvage therapies employed.
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Stefanski HE, et al. Abstract 126. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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