Pembrolizumab Plus Ifosfamide, Carboplatin, and Etoposide in Relapsed or Refractory Classical Hodgkin Lymphoma

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In a phase II trial reported in JAMA Oncology, Locke J. Bryan, MD, and colleagues found that the combination of pembrolizumab with ICE chemotherapy (a regimen including ifosfamide, carboplatin, and etoposide) produced a high rate of complete response in patients with relapsed or refractory classical Hodgkin lymphoma who were candidates for autologous stem cell transplantation (SCT).

As stated by the investigators, “To 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[al] Hodgkin lymphoma in patients destined for an autologous SCT.”

Locke J. Bryan, MD

Locke J. Bryan, MD

Study Details

In the U.S. investigator-initiated multicenter study, 37 evaluable patients with relapsed or refractory disease after one or two lines of chemotherapy were enrolled between April 2017 and October 2020. Patients received two cycles of pembrolizumab at 200 mg on day 1 with standard salvage ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then one cycle of pembrolizumab alone followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) response assessment. The primary endpoint was complete response rate. The null hypothesis of complete response rate of 50%, based on prior reports with chemotherapy alone, was rejected if complete response rate was at least 70%.

Patients with complete response proceeded to autologous SCT.

Key Findings

Complete response on FDG-PET/CT imaging was observed in 32 (86.5%, 95% confidence interval [CI] = 71.2%–95.5%) of 37 patients, thus meeting the primary endpoint. Partial response was observed in an additional four patients (10.8%), yielding an overall response rate of 97.3% (36 patients).

New areas of FDG-PET/CT positivity in two patients were biopsied, showing noncaseating granuloma in one and a reactive lymph node in the other.

A total of 35 patients proceeded to autologous SCT. Seven received radiation as part of the conditioning regimen, and four received radiation after transplantation. As stated by the investigators, “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.”

Median follow-up was 24 months (range = 0.5–35.4 months). Estimates of progression-free survival and overall survival at 2 years were 87.2% (95% CI = 77.3%–98.3%) and 95.1% (95% CI = 88.8%–100%), respectively.

Among 42 patients in the safety population, adverse events of any grade considered related to pembrolizumab occurred in 81%. Serious adverse events considered related to pembrolizumab occurred in five patients (12%). No cases of hypothyroidism or hyperthyroidism, hepatitis, or colitis were reported. Macular papular rash (all grade 1 or 2) occurred in 13 patients (32%).

The investigators concluded, “Results 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[al] Hodgkin lymphoma eligible for an autologous SCT.”

Jane N. Winter, MD, of the Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. For full disclosures of the study authors, visit


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