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Allogeneic stem-cell transplantation (allo-SCT) after CAR T-cell failure led to durable remissions in patients with relapsed/refractory large B-cell lymphoma (LBCL), according to data from a multicenter series.

The results showed a median progression-free survival (PFS) of 10 months in 88 patients and a median overall survival (OS) of 21 months. Both outcomes compared favorably with historical results for post-CAR T-cell progression, which is associated with a from progression.

"Allogeneic transplant after CAR-T therapy led to durable responses at 1 year, and this was similar to outcomes seen after allo-transplant for large B-cell lymphoma in general," said Joanna Zurko, MD, of the Medical College of Wisconsin in Milwaukee, during the Transplantation & Cellular Therapy Meetings. "We saw no unexpected or prolonged issues with hematopoiesis and no signals of increased GVHD [graft-versus-host disease] or other unexpected complications.

"Patients who were not in complete remission at the time of allo and those who received two or more intervening lines of therapy had worse outcomes, but we need more long-term follow-up to confirm the durable remission rate and curative potential of allo after CAR-T failure," she said. "On the basis of these findings, we believe that transplant-eligible patients, at least those who achieve a CR after CAR-T failure should be considered for allogeneic transplant at this time."

The data may help inform decisions related to one of the key challenges of CAR T-cell therapy. Although the therapy produces in relapsed/refractory LBCL, responses are durable in only . Median OS after CAR-T failure is poor, said Zurko.

Limited Data for Allo-SCT After CAR-T

Allo-SCT has curative potential for a subgroup of patients with relapsed/refractory LBCL, but limited data exist to document the safety and efficacy of allo-SCT after CAR-T therapy, she explained. Most of the evidence has come from a small patient series.

"Whether patients who fail CAR-T derive similar benefit with allo-transplant and to whom to offer this modality remains unknown," said Zurko.

She presented data for patients treated at 18 U.S. academic medical centers. The analysis was limited to patients who received CAR T-cell therapy targeting the CD19 antigen but included investigational and multitargeted CAR-T therapies. The primary endpoints were PFS, OS, nonrelapse mortality (NRM), progression/relapse, acute and chronic GVHD, and neutrophil and platelet recovery. Patients in complete remission with CAR T-cell therapy were excluded.

The 88 patients included in the analysis had a median age of 54, and men accounted for 72% of the total study population. Most of the patients had de novo diffuse LBCL (59%) or transformed indolent lymphoma (26%). A fourth of the patients had received a prior autologous SCT, and they had a median three lines of treatment prior to CAR T-cell therapy. About a third of the patients had a complete remission as best response to CAR-T therapy and a similar proportion had partial responses.

The patients had received as many as seven lines of therapy between CAR-T failure and allo-SCT, Zurko said. About half the patients (45) were in complete remission prior to allo-SCT and a fourth had partial responses. The median duration from CAR-T failure to allo-SCT was 8.4 months. Three fourths of the patients received reduced-intensity/nonmyeloablative conditioning therapy. Donor type was matched-unrelated in 39% of cases, haploidentical in 30%, and matched-related in 26%.

The transplants were associated with a 94% rate of neutrophil recovery at 28 days and platelet recovery in 89% by day 100, she noted. One primary graft failure occurred. The incidence of acute grade II-IV GVHD at 100 days was 34%, including grade III-IV in 10%. The cumulative incidence of chronic GVHD at 1 year was 30% overall, including severe GVHD in 4% of patients.

In addition to the median PFS of 10 months and median OS of 21 months, the 1-year PFS was 45% and the 1-year OS was 59%. The 1-year NRM was 22%, and a third of the patients had relapse or progression at 1 year.

Future Role of Transplant

By multivariate analysis, patients in complete remission at allo-SCT had better OS (HR 4.3, 95% CI 1.6-11.6) as compared with patients who were in partial remission, Zurko said, adding that the investigators found no predictors of PFS, NRM, or progression/relapse. Additionally, patients who had received fewer than two lines of therapy between CAR-T failure and allo-SCT fared better than those who received two or more intervening lines of therapy.

During a discussion that followed the presentation, Zurko was asked to speculate about the status of autologous SCT as CAR T-cell therapy moves into second-line treatment for relapsed/refractory LBCL.

"We have good data that even patients who fail three or more lines of therapy still have good outcomes with autologous transplantation, and certainly the nonrelapse mortality of autologous transplant is significantly lower than that of an allogeneic transplant," she said. "Certainly patients who achieve a complete or partial response after CAR T-cell therapy should be strongly considered for autologous transplant if they haven't already received one."

"At 1 year we are actually seeing reasonable outcomes with allogeneic transplant, on par with some 1-year outcomes for CAR-T, so I think allo-transplant should not be ignored," she added.

In response to another question, Zurko said patients who had no intervening therapy between CAR-T and allo-SCT had poor outcomes, including high mortality. However, she noted, the researchers do not have sufficient data to recommend allo-SCT as consolidation for patients who achieve a partial response with CAR T-cell therapy.

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