Allogeneic HSCT induces durable response in B-cell lymphoma
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SALT LAKE CITY — Patients with relapsed or refractory large B-cell lymphoma who failed chimeric antigen receptor T-cell therapy achieved durable responses with allogeneic hematopoietic stem cell transplantation, according to study results.
The results — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — showed no unexpected or prolonged adverse events with hematopoiesis, as well as no signals of increased graft-versus-host disease risk or other serious complications.
Rationale
“There are currently three FDA approved CAR T-cell therapies targeting the CD19 antigen to treat relapsed or refractory large-B cell lymphoma. However, most patients will progress following CAR T-cell therapy, with durable remission rates ranging between 30% and 40%,” researcher Joanna C. Zurko, MD, hematologist at the Medical College of Wisconsin, told Healio.
Outcomes for patients who progress following anti-CD19 CAR-T cell therapy are poor, with a median OS less than 6 months.
Allogeneic HSCT has curative potential for select patients with relapsed or refractory large B-cell lymphoma, with data in the pre-CAR T-cell therapy era showing 3-year PFS between 36% and 38%, Zurko added.
“Despite this, we have limited data on the efficacy and toxicities of allogeneic HSCT after receipt of CAR-T cell therapy, limited to small series of less than 10 patients,” she said. “Therefore, whether patients who fail CAR T-cell therapy will derive similar benefit with allogeneic HSCT — and to whom to offer this modality — remains unknown.”
Methods
Zurko and colleagues conducted a multicenter retrospective analysis that included 88 patients (median age, 54 years; 66% white; 20% Hispanic; 6.8% Black) who underwent allogeneic HSCT after CAR T-cell therapy failure.
More than half (59%) had de novo diffuse large B-cell lymphoma, whereas 26% had transformed DLBCL and 9.1% had primary mediastinal B-cell lymphoma.
Patients underwent a median three (range, 1-7) lines of therapy prior to CAR-T, and 25% underwent prior autologous HSCT.
Most patients (71%) had achieved either a complete response (35%) or partial response (36%) to CAR-T.
Study participants underwent a median one (range, 0-7) lines of therapy between CAR-T and allogeneic HSCT. Half (51%) were in complete remission at the time of allogeneic HSCT, 25% were in partial remission, and 24% had either stable disease or progressive disease.
Key findings
Median follow-up was 15 months.
Results showed median OS of 21 months and median PFS of 10 months.
At 1 year, researchers reported OS of 59% and PFS of 45%, with a 33% relapse/progression rate and a 22% nonrelapse mortality rate.
Most patients (94%) achieved neutrophil recovery by 28 days (median time to recovery, 16 days) and 89% of patients achieved platelet recovery by 100 days (median time to recovery, 18 days). Researchers reported one case of primary graft failure.
At 100 days, 34% of patients had developed grade 2 to grade 4 acute graft-versus-host disease, and 10% had grade 3/grade 4 acute GVHD. Approximately one-third (30%) developed chronic GVHD by 1 year, with 4% developing severe cases.
Multivariate analysis showed that patients who received two or more lines of intervening therapy between CAR T-cell therapy and allogeneic HSCT and those who were not in complete remission at the time of transplant achieved significantly shorter PFS, OS and non-relapse mortality.
Implications
“The findings of this analysis will help us address the critical question of what treatment modalities to offer patients following CAR T-cell therapy failure given outcomes for these patients are so poor,” Zurko told Healio. “These data demonstrate that there is clearly a role for allogeneic HSCT in select patients with CAR-T cell therapy failure, with a 1-year PFS and OS not dissimilar to the 1-year PFS and OS of patients treated on the ZUMA-1 trial.”
Patients who fail CAR T-cell therapy should receive highly active therapies in the first-line setting and ideally undergo allogeneic HSCT while in complete remission, Zurko added.
“I have previously presented data demonstrating that only 6% of patients experiencing CAR-T failure subsequently received an allogeneic HSCT, suggesting this modality may currently be significantly underutilized in patients with CAR T-cell therapy failure,” she said. “Therefore, fit patients with CAR T-cell therapy failure should be referred to a transplant center as soon as possible.”
Although responses shown here at 1 year are promising, more long-term follow-up is needed to confirm the durable remission rate and curative potential of allogeneic HSCT after CAR T-cell therapy failure, Zurko added.
“The role of consolidative allogeneic HSCT after CAR T-cell therapy also needs to be further explored,” she said. “There were five patients in our cohort with a best response of partial response with CAR T-cell therapy who then received an allogeneic HSCT while in partial remission with no lines of intervening therapy. The outcomes in this group were quite poor, with 80% of patients experiencing disease progression at last follow-up. Whether this finding will hold up in a larger sample size needs to be further explored.”
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Zurko JC, et al. Abstract 8. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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