Allogeneic hematopoietic cell transplantation (alloHCT) after treatment with programmed cell death 1 (PD-1) monoclonal antibodies was found to be associated with overall favorable outcomes in patients with classic Hodgkin lymphoma, according to the results of a study published in Leukemia.
The international, retrospective study analyzed data from patients at 33 transplant centers, including 23 in the United States, to assess the role, timing, and optimal method of alloHCT after PD-1 blockade. The endpoints of the study included overall survival (OS), progression-free survival (PFS), graft-vs-host disease (GVHD)-free and relapse-free survival (GRFS), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and acute and chronic GVHD.
The cohort included 209 patients with classic Hodgkin lymphoma who underwent alloHCT after PD-1 blockade. The participants (median age, 31.5 years [range 17-68]; 60% men) received a median of 10 doses of a PD-1 monoclonal antibody, with a median interval of 81 days from the last dose to alloHCT. After PD-1 monoclonal antibody therapy, 109 patients (52%) proceeded directly to alloHCT, and 100 patients (48%) had intervening salvage therapy.
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After a median follow-up of 24 months (range, 1-70 months) in survivors, GRFS was 47% (95% CI, 40-54), PFS was 69% (95% CI, 61-75), and OS was 82% (95% CI, 76-87).
The 180-day cumulative incidences of any grade, grades 2 to 4, and grades 3 to 4 acute GVHD were 54% (95% CI, 47-61), 37% (95% CI, 30-43), and 15% (95% CI, 11-21), respectively. A total of 11 patients (5%) died from complications of acute GVHD.
The 2-year cumulative incidence of NRM was 14% (95%, CI 9-19), and the most common causes of NRM were GVHD (11 patients) and infectious complications (7 patients). The 2-year CIR was 18% (95% CI, 12-23) for the overall cohort. For chronic GVHD, the 2-year cumulative incidence was 34% (95% CI, 27-41).
The use of post-transplant cyclophosphamide (PTCy) was associated with a lower cumulative incidence of chronic GVHD compared with other treatments (25% vs 46%, P = .002). Multivariable analysis showed that PTCy use was associated with a lower risk of chronic GVHD for haploidentical/PTCy (hazard ratio [HR], 0.5; P =.026) and nonhaploidentical/PTCy patients (HR, 0.2; P =.011) compared with nonhaploidentical/no PTCy patients.
Participants who had an interval of more than 80 days from PD-1 to alloHCT had a lower risk of grades 2 to 4 (HR, 0.4, P =.04) and grades 3 to 4 (HR, 0.4, P =.01) acute GVHD. Patients who had intervening salvage therapy had an almost 3-fold increase in CIR according to the multivariable analysis.
The retrospective study has several limitations, noted the investigators. Because alloHCT candidacy, timing, and transplant strategies were chosen by treating physicians, selection bias is possible. In addition, the study did not include a centralized radiologic review, and imaging modality and timing of response assessment varied among the centers and individual patients.
“Our cohort strongly suggests that the use of PTCy significantly improves both GRFS and PFS,” the study authors commented. “Based on these findings, PTCy appears to be the optimal approach for patients undergoing alloHCT after PD-1 blockade.”
Disclosure: Some of the authors reported affiliations with pharmaceutical, biopharmaceutical, and biotechnology companies. Please see the original reference for a full list of disclosures.
Reference
Merryman RW, Castagna L, Giordano L, et al. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia. Published online March 3, 2021. doi:10.1038/s41375-021-01193-6
