Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma

Abstract

ImportanceTo our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant.ObjectiveTo evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose–positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma.Design, Setting, and ParticipantsA single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT.InterventionsTwo cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment.Main Outcomes and MeasuresThe primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety.ResultsForty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting.Conclusions and RelevanceResults suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant.Trial RegistrationClinicalTrials.gov Identifier: NCT03077828

Beyond Chemotherapy: Present and Future Perspectives in the Treatment of Lymphoproliferative Disorders

“…Multiple phase II trials have added BV to different salvage chemo regimens: in combination with bendamustine, ICE, IGEV, ESHAP, or DHAP, the CR rate ranges from 62% to 80% [91][92][93][94][95]. Studies with pembrolizumab show the most promising results, achieving complete remission rates before transplant of 87% in combination with ICE and 92% in combination with GVD with manageable toxicities, warranting further investigation in larger trials [96,97].…”

Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

“…Table 1. An overview of several malignancies commonly treated with ICIs (alone or in combination therapy) [15,17,19,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. NSCLC-non-small cell lung cancer, SCLC-small cell lung cancer, MSI-H or dMMR CRC-Microsatellite-high or deficient mismatch repair colorectal carcinoma, BCC-Basal cell carcinoma, CSCC-cutaneous squamous cell carcinoma, ESCC-esophageal squamous cell carcinoma.…”

The shifting roles and toxicities of cellular therapies in B‐cell malignancies

“…22 Another study found that pembrolizumab combined with ICE had an OR rate of 97% and a CR rate of 86%. 23 An ongoing trial comparing nivolumab-AVD and brentuximab vedotin (BV)-AVD has shown superior PFS rates in the BV-AVD arm. 24…”