Immune checkpoint inhibitors with transplant improve survival in relapsed Hodgkin lymphoma
Key takeaways:
- Pre-transplant immune checkpoint inhibitors improved survival in relapsed Hodgkin lymphoma compared with chemotherapy.
- Graft-versus-host disease occurred more often with checkpoint inhibitors.
Pre-transplant immune checkpoint inhibitors extended survival for patients with relapsed classic Hodgkin lymphoma compared with chemotherapy, according to results of a retrospective study.
However, patients who received immune checkpoint inhibitors (ICIs) developed graft-versus-host disease at higher rates.
“ICI treatment before allogeneic blood or marrow transplantation (alloBMT) can improve survival outcomes — particularly by reducing relapse rates, which is critical for patients with relapsed/refractory classic Hodgkin lymphoma,” Suman Paul, MBBS, PhD, assistant professor of oncology at Johns Hopkins School of Medicine, told Healio. “However, it is crucial to carefully monitor for complications such as GVHD, and the increased GVHD risk could be mitigated by increasing the duration of immunosuppression after alloBMT.”
Background and methods
ICIs have induced high response rates for individuals with relapsed or refractory classic Hodgkin lymphoma, according to study background.
These patients often move on to receive autologous blood or marrow transplantation (autoBMT) or alloBMT.
Previous studies showed prior ICI treatment can increase morbidity or mortality after alloBMT, specifically related to GHVD.
Paul and colleagues found post-transplant cyclophosphamide can mitigate those risks, as patients treated with ICIs, transplantation and cyclophosphamide achieved superior 3-year PFS compared with individuals treated with pre-transplant chemotherapy.
However, long-term survival of patients treated with ICIs followed by alloBMT had not been well established, Paul said.
Researchers evaluated 147 consecutive patients with classic Hodgkin lymphoma treated with nonmyeloablative conditioning alloBMT and post-transplant cyclophosphamide at The Sidney Kimmel Comprehensive Center at Johns Hopkins between November 2004 and August 2023.
A comparable percentage of the cohort received ICIs (48.3%) or chemotherapy without ICIs (51.7%).
Investigators reported median follow-up of 22.7 months (range, 2.6-88.6) in the ICI cohort (median age, 32 years; range, 26-40; 55% men), and 65.4 months (range, 4.5-206.9) in the chemotherapy cohort (median age, 36 years; range, 28-45; 53% men).
Five-year OS, PFS and GVHD incidence served as primary endpoints.
Results and next steps
Paul and colleagues reported higher 5-year estimated PFS (84% vs. 53%; HR = 0.4; 95% CI, 0.2-0.81) and OS (91% vs. 66%; HR = 0.39; 95% CI, 0.16-0.98) in the ICI group.
Because patients only started receiving ICIs in 2015, researchers conducted a subgroup analysis of those who underwent alloBMT between 2015 and 2023. Results showed a significant difference in median PFS between those who received chemotherapy vs. ICIs (46.2 months vs. not reached; HR = 0.38; 95% CI, 0.17-0.89).
The ICI cohort also had a lower cumulative incidence of relapse at 3 years (7% vs. 26%; subdistribution HR = 0.24; 95% CI, 0.08-0.68).
Full donor chimerism at day 60 occurred less often in the ICI cohort (60.5% vs. 84.2%), and graft failure occurred more often (16.9% vs. 5.3%, P = .03).
The ICI cohort had higher 12-month incidence of acute grade 3 to grade 4 GVHD (20% vs. 7%; 95% CI, subdistribution HR = 3.16; 95% CI, 1.13-8.81), but the two cohorts had similar 24-month incidence of chronic GVHD.
Researchers found patients in the ICI cohort who received short-duration immunosuppression with tacrolimus — until day 60 — had significantly higher 12-month incidence of acute grade 3 to grade 4 GVHD than those who received immunosuppression for at least 180 days (21% vs. 7%; HR = 2.92; 95% CI, 1.1-7.7).
“These data suggest ... the GVHD risk can be mitigated by immunosuppression until day 180,” Paul and colleagues wrote.
Researchers acknowledged study limitations, including its retrospective nature and a time bias, since ICI therapy did not begin until 2015.
“Future research should focus on identifying the underlying mechanisms driving increased graft failure and GVHD in patients treated with ICI before alloBMT,” Paul told Healio.
“It is important to emphasize that while ICI therapy can improve survival in patients with classic Hodgkin lymphoma undergoing alloBMT, alloBMT is not the only option for patients who relapse,” he added. “Studies have shown that patients who had relapsed classic Hodgkin lymphoma treated with ICI can also benefit from high-dose chemotherapy followed by autoBMT. As direct studies comparing alloBMT with autoBMT are lacking, the [optimal] consolidation method remains a bit unclear.”
For more information:
Suman Paul, MBBS, PhD, can be reached at spaul19@jhmi.edu.
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