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Second-Line Pembrolizumab Plus Chemotherapy Regimen for Relapsed or Refractory Classic Hodgkin Lymphoma


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Alison J. Moskowitz, MD

Alison J. Moskowitz, MD

In a phase II trial reported in the Journal of Clinical Oncology, Alison J. Moskowitz, MD, and colleagues found that second-line therapy with pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) in relapsed or refractory classic Hodgkin lymphoma produced responses in all patients and complete response in 95%. After subsequent high-dose therapy/autologous hematopoietic cell transplantation (HDT/AHCT) in complete responders, all remained in remission at the time of this analysis.

Study Details

The investigator-initiated trial enrolled 39 transplant-eligible patients (16 with primary refractory and 23 with relapsed disease) between August 2018 and October 2020 at Memorial Sloan Kettering Cancer Center and the University of Miami Sylvester Comprehensive Cancer Center. Patients received two to four cycles of pembrolizumab at 200 mg on day 1 and gemcitabine at 1,000 mg/m2, vinorelbine at 20 mg/m2, and liposomal doxorubicin at 15 mg/m2 on days 1 and 8 every 21 days.

Patients were assessed by fluorodeoxyglucose–positron-emission tomography/computed tomography (FDG-PET/CT) after two and four cycles of treatment. Patients with complete response (defined as Deauville ≤ 3) after two cycles were eligible to proceed to HDT/AHCT; other patients received an additional two cycles followed by FDG-PET/CT and were considered for HDT/AHCT. The primary endpoint was complete response after up to four cycles of pembrolizumab plus GVD.

Responses

Among the 39 patients, 31 received 2 cycles of pembrolizumab plus GVD and 8 received 4 cycles. Among 38 evaluable patients, 35 (92%) had complete responses after 2 cycles of pembrolizumab plus GVD and 3 (8%) had partial responses. After 4 cycles, response was achieved in all 38 (100%), with a complete response in 36 (95%).

Among the 36 patients proceeding to HDT/AHCT, 2 received pre-HDT/AHCT involved-site radiation and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance, as permitted by protocol, for a median of 5 cycles; 1 of the 13 patients received brentuximab vedotin plus pembrolizumab as part of a clinical trial. Of the two patients not proceeding to HDT/AHCT, one with a complete response after two cycles of pembrolizumab plus GVD withdrew from the study for personal reasons. The other patient declined HDT/AHCT and received off-study single-agent pembrolizumab; this patient remained on pembrolizumab and is in remission at 16 months after completion of pembrolizumab plus GVD.

At the time of last follow-up, at a median of 13.5 months (range = 2.7–27.1 months) after HDT/AHCT, all patients undergoing transplantation remained alive and in remission.

Adverse Events

The most common adverse events of any grade among all 39 enrolled patients were rash (49%), increased aspartate aminotransferase/alanine aminotransferase (41%), oral mucositis (38%), nausea (36%), and fatigue (31%). A total of 12 grade 3 and no grade 4 adverse events were reported; grade 3 adverse events consisted of transaminitis in four patients (10%), neutropenia in four (10%), mucositis in two (5%), hyperthyroidism in one (2%), and rash in one (2%). Immune-related adverse events of any grade included hyperthyroidism in five patients (13%); all cases of transaminitis and rash were considered immune-related. Treatment delays (median = 6 days) were required in nine patients (23%). Dose reduction of any component of GVD was required in two patients (5%).

The investigators concluded: “Second-line therapy with pembrolizumab plus GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with [relapsed/refractory classic Hodgkin lymphoma] to HDT/AHCT.”

Dr. Moskowitz, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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