Pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy in relapsed or refractory Hodgkin lymphoma: 5-year update of a multicenter, Phase 2 trial
Year: 2025
Type: conference-abstract
Abstract: Background: The incorporation of novel agents such as brentuximab vedotin (BV) and immune checkpoint blockade (ICB) into salvage therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) has significantly improved long-term outcomes for patients. A phase II trial assessed the safety and efficacy of pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (pembrolizumab-GVD) in transplant-eligible patients with rel/rel cHL, and demonstrated a complete response (CR) rate of 95% and progression-free survival (PFS) of 100% at 13.5 months. Herein, we present an updated analysis of this phase II trial at 5 years (ClinicalTrials.gov identifier: NCT03618550). Methods: This was an investigator-initiated, single-arm, phase II trial conducted at Memorial Sloan Kettering Cancer Center and the University of Miami Sylvester Comprehensive Cancer Center. Eligible patients had biopsy-proven rel/ref cHL following a single line of multi-agent chemotherapy, were aged at least 18 years, and had an Eastern Cooperative Oncology Group (ECOG) performance score of <2. Patients received pembrolizumab 200mg intravenous (IV) (day 1), gemcitabine 1,000mg/m2IV (days 1 and 8), vinorelbine 20mg/m2(days 1 and 8), and liposomal doxorubicin 15mg/m2IV (days 1 and 8) in 21-day cycles. Those who achieved CR following two or four cycles of pembrolizumab-GVD proceeded to high-dose therapy with BEAM (carmustine, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (HDT/AHCT). The primary endpoint was CR following salvage pembrolizumab-GVD; secondary endpoints were PFS and overall survival (OS). Results: 39 patients were enrolled. The median age was 38 (range 21 to 71), and 46% of patients were men. At the time of enrollment, 41% of patients had Lugano stage I or II disease, while 59% of patients had stage III or IV disease. Twelve patients (31%) had extranodal disease. Sixteen (41%) patients had primary refractory disease, while 23 patients (59%) had relapsed disease, with 15 of 23 patients relapsing within 1 year. Most patients received ABVD in the front-line setting; no patients received immune checkpoint blockade as part of front-line therapy. Thirteen patients (33%) received maintenance post-ASCT with BV (n=12) or BV-nivolumab (n=1, as part of a clinical trial), for a median of 5 cycles (range 1-11). Two patients (5%) received radiation therapy (RT) prior to HDT/ASCT. Of 38 response-evaluable patients, the CR and overall response rate (ORR) after up to 4 cycles of pembrolizumab-GVD were 95% and 100%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, with 24 of 36 patients (67%) experiencing engraftment syndrome post-transplant requiring treatment with systemic steroids. After a median follow-up of 57 months, 1 of 38 patients experienced disease recurrence (23 months after HDT/AHCT), and two of 38 patients died from non-relapse related causes (41 months and 33 months after HDT/AHCT, from sudden cardiac death during exercise and complications of auto-immune hemolytic anemia, respectively). Estimated 5-year PFS and OS were 91% and 94%, respectively. No new safety signals were identified with extended follow-up. Conclusion: Pembrolizumab-GVD followed by consolidative HDT/AHCT achieves durable and long-term responses in patients with rel/ref cHL, with a manageable safety profile. Based on the robust long-term outcomes seen in this study, our group is evaluating whether HDT/AHCT can be omitted, with a randomized study comparing HDT/AHCT versus pembrolizumab maintenance in patients who achieve CR to pembrolizumab-GVD currently underway.
Source: Blood
Authors: Kishan Patel, Gunjan Shah, Heiko Schoder, Nivetha Ganesan, Esther Drill, Helen Hancock, Theresa Davey, Alayna Santarosa, Natasha Galasso, Anita Kumar, Oscar Lahoud, Paul Hamlin, Colette Owens, Philip Caron, Andrew Intlekofer, Steven Horwitz, Lorenzo Falchi, William Johnson, Lia Palomba, Ariela Noy, Matthew Matasar, Gilles Salles, Santosha Vardhana, Gottfried von Keudell, Joachim Yahalom, Ahmet Dogan, Andrew Zelenetz, Craig Moskowitz, Alison Moskowitz
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417008354