Pembrolizumab plus conventional chemotherapy appears effective as second-line treatment in patients with classic Hodgkin lymphoma who are eligible for transplant, according to research published in JAMA Oncology.

The complete response (CR) rate seen in patients treated with this combination — pembrolizumab plus ifosfamide, carboplatin, and etoposide (ICE) — was superior to CR rates historically seen with second-line chemotherapy alone. 

This phase 2 trial ( Identifier: NCT03077828) included 42 patients with relapsed or refractory Hodgkin lymphoma who were eligible for autologous hematopoietic stem cell transplant (auto-HSCT).

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A total of 37 patients were evaluable for the primary endpoint. Their median age was 34 (range, 19-70) years, and 68% were women. A majority of patients (57%) had stage III-IV disease, 43% had primary refractory disease, 32% had relapsed within 1 year of completing first-line therapy, and 16% had bulky disease. For first-line therapy, most patients (92%) received doxorubicin, vinblastine, and dacarbazine, with or without bleomycin.

Study treatment consisted of pembrolizumab and ICE for two 21-day cycles, followed by stem cell mobilization and collection, and an additional cycle of pembrolizumab alone. Patients could also receive another cycle of combination pembrolizumab and ICE at the investigators’ discretion.

Five patients received the additional cycle of pembrolizumab and ICE, and 35 patients went on to auto-HSCT. Seven patients had radiation prior to HSCT, and 4 had radiation after.

Response was assessed 14 to 22 days after pembrolizumab monotherapy. The overall response rate was 97.3%. Of 36 responders, 4 (10.8%) had a partial response. 

The CR rate was 86.5% (n=32). This met the study’s primary endpoint, which was improvement over estimated historical outcomes with second-line chemotherapy from 50% to at least 70%. 

Forty patients were evaluable for progression-free survival (PFS), and 42 were evaluable for overall survival (OS). At a median follow-up of 24 months, the median PFS and OS were not reached. The 2-year PFS rate was 87.2%, and the 2-year OS rate was 95.1%.

All 42 patients were evaluable for safety. The most common grade 3-4 adverse events (AEs) occurring at any time during treatment were platelet count decrease (95%), lymphocyte count decrease (93%), white blood cell count decrease (93%), neutropenia (91%), and anemia (76%).

Thirty-four patients (81%) had AEs attributable to pembrolizumab. The rate of grade 3-4 AEs in this group was 52.4%. These AEs included cytopenias, elevated aspartate aminotransferase, elevated alanine aminotransferase, hyponatremia, hypophosphatemia, and fatigue. Five patients had 6 serious AEs considered possibly related to pembrolizumab.

“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 Hodgkin lymphoma eligible for an autologous stem cell transplant,” the researchers wrote.

Disclosures: This research was supported by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Bryan LJ, Casulo C, Allen PB, et al. 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. JAMA Oncol. Published online March 16, 2023. doi:10.1001/jamaoncol.2022.7975