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Progressive disease after anti-CD19 CAR T-cell therapy predicts poor lymphoma survival
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SAN DIEGO — Patients with large B-cell lymphoma who experienced progressive disease following CD19-specific chimeric antigen receptor T-cell therapy had poor long-term outcomes, according to results presented at ASH Annual Meeting and Exposition.
Early progression in particular was associated with poor survival, highlighting the need to develop effective strategies for patients who don’t attain remission and to improve the durable complete response rate.
“The study specifically looked at outcomes for patients with large B-cell lymphomas who showed evidence of progressive disease after receiving a CD19-specific CAR T-cell product,” Victor A. Chow, MD, senior hematology-medical oncology fellow at Seattle Cancer Care Alliance clinical research division at Fred Hutchinson Cancer Research Center and in the division of medical oncology at University of Washington, told HemOnc Today. “The idea for this study stems from the question of ‘what do we do next?’ when patients come see us after they have progressed following CAR T-cell therapy.”
Chow and colleagues identified 58 patients (median age, 60 years; 65% men) with diffuse large B-cell lymphoma, high-grade B-cell lymphoma, transformed follicular lymphoma and primary mediastinal large B-cell lymphoma who received CD19-specific chimeric antigen receptor (CAR) T-cell therapy.
OS served as the study’s primary endpoint.
“We looked at several other factors that may contribute to OS differences,” Chow said.
Those included timing of progression (initial vs. late), and the use of bridging therapy between T-cell collection and CAR T-cell infusion.
“We also looked at the administration of any subsequent therapy after evidence for progression and whether it affected OS,” he said.
The median duration between CAR T infusion to progression was 42 days (range, 11-609). Fifty-three percent of patients experienced early progressive disease, defined as those who had evidence of disease progression on the initial response assessment.
Median follow-up after progression was 4.2 months.
Median OS was 5.3 months for the overall cohort after progression. For those with initial progressive disease, median OS was 3.75 months, whereas those who had delayed progression — which included a complete or partial response or stable disease on the initial response assessment, followed by progression or subsequent anti-lymphoma therapy — had a median OS of 13.42 months.
Initial progressive disease increased risk for death (HR = 2.37, 95% CI, 1.19-4.75).
Chow acknowledged the excitement surrounding CAR T cells resulting from positive outcomes for a group of patients with little to no viable options remaining for long-term disease control, but urged clinicians to be aware of the reality that a large proportion of patients undergoing this treatment do not benefit from durable disease control at the moment.
“Ultimately, our results should not be surprising to providers who treat lymphomas on a day-to-day basis,” Chow said. “However, we should take into context that those individuals who received subsequent therapy after evidence for progression potentially had better patient and/or disease specific characteristics such as less aggressive disease or better performance status, which allowed for them to receive subsequent therapy.”
Three-quarters of patients received one or more subsequent therapies after progressive disease, including a second CAR T infusion, targeted therapy, chemotherapy with or without rituximab (Rituxan; Genentech, Biogen), other immunotherapy, radiotherapy, intrathecal chemotherapy and allogeneic hematopoietic stem cell transplant.
There was no difference in survival if second CAR T infusion, targeted therapy or chemotherapy was the next line therapy compared with others.
Four patients underwent allogeneic HSCT, two of whom remained alive at the time of the analysis.
“Those who received bridging therapy had a numerically inferior OS compared with those who did not receive bridging therapy, but this was not statistically significant,” Chow said.
He added that patients able to receive subsequent therapy of any kind survived longer, but again, may be a select group of individuals who harbored inherently better characteristics.
“The main takeaway from this study is that patients who progress after CAR T-cell therapy have poor outcomes, particularly those patients who progress soon after,” Chow said. “The unanswered question is how to best care for them, as there are no data to guide us at the moment due to the novelty of CAR T-cell therapy and its use in the relapsed/refractory setting. However, from our study, it does appear that patients who received any form of therapy after progression did survive longer.”
That said, Chow offered a few potential ways of dealing with this patient population.
“One is to make sure all patients have HLA typing so that if they do progress, a matched donor can be identified quickly for an allogeneic stem-cell transplant,” he said. “Another option is to be cognizant of clinical trials for these patients. If we pre-screen, we may enroll them on their next-line therapy right when disease progression occurs.”
Chow also suggested obtaining preauthorization for novel agents that don’t yet have FDA approval for large B-cell lymphomas.
“CAR T-cell therapy has dramatically changed the landscape for the treatment of relapsed/refractory large B-cell lymphomas. As exciting as CAR T-cell therapies have been, there are still many patients who unfortunately progress,” Chow said. “We hope our data shed light for the development of more effective strategies to help patients obtain durable complete responses, prevent progressive disease, and to improve their overall survival.”– by Rob Volansky
Reference:
Chow V, et al. Abstract 94. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.
Disclosures : Chow reports no relevant financial disclosures. Please see the abstract for the full list of disclosures.