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A Novel Checkpoint Inhibitor Regimen for Classic Hodgkin Lymphoma
Most patients with classic Hodgkin lymphoma (cHL) are cured by front-line therapy. Those refractory to initial treatment or experiencing later relapse typically undergo combination chemotherapy followed by autologous stem-cell transplantation (ASCT) with curative intent. Given the high single-agent activity of immune checkpoint inhibitors in cHL, investigators evaluated treatment with pembrolizumab in combination with ifosfamide, carboplatin, and etoposide (ICE) in an industry-supported, multicenter, single-arm phase 2 study. Stem cells were collected after two cycles of pembrolizumab-ICE. After one additional cycle of pembrolizumab alone, a restaging positron emission tomography/computed tomography scan (PET2) was performed; patients with complete response (CR; defined as Deauville score ≤3) proceeded to ASCT.
The trial enrolled 42 transplant-eligible adults who had received 1 or 2 prior treatment regimens. Of 37 evaluable patients, median age was 34 years, 67% were female, and 16% were African American; 43% had primary refractory cHL and 32% had relapsed within 1 year of front-line therapy. Five patients received an additional cycle of pembrolizumab-ICE to accommodate timing of ASCT, and 11 patients received radiation therapy before or after ASCT. The PET2 overall response rate was 97.3%, with CR in 86.5%; 2-year progression-free survival was 87.2% and overall survival was 95.1%. No unexpected toxicities were identified aside from one episode of acute respiratory failure possibly related to engraftment syndrome and pembrolizumab.
The study exceeded its primary endpoint of achieving a CR rate of at least 70% — an increase over historical second-line treatment CR rates of 50%. Further analysis of concurrent checkpoint inhibitor combinations with chemotherapy in the second line are warranted. However, results from a phase 3 trial of front-line nivolumab plus adriamycin, vinblastine, and dacarbazine (AVD) versus brentuximab vedotin plus AVD in cHL (SWOG S1826; NCT03907488) are anticipated at the ASCO 2023 Annual Meeting. If that study supports front-line checkpoint inhibitor therapy, efficacy of this therapy in the relapsed disease setting will need reevaluation.
Bryan LJ et al.
Title: Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classic Hodgkin lymphoma: A multi-institutional phase 2 investigator-initiated nonrandomized clinical trial.
Source: JAMA Oncol 2023 Mar 16; [e-pub]. (Abstract/FREE Full Text)