Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin (P-GVD) for Classical Hodgkin Lymphoma (CHL) in the Real-World Setting

Introduction: Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin (P-GVD) has become a commonly employed regimen for the treatment of relapsed or refractory classical Hodgkin lymphoma (CHL), often preceding autologous stem cell transplant in patients with good response. The utilization of P-GVD is based on a 38-evaluable patient prospective trial (Moskowitz et al. JCO 2021). There remains minimal data regarding the efficacy of this regimen in a larger, real-world cohort.

Methods:Patients with CHL who received P-GVD at 9 United States centers were retrospectively evaluated to estimate efficacy and safety, with a focus on the second line use of this regimen. Demographic and clinical data were extracted from medical records. Responses reflected Lugano criteria per local investigator assessment. Study objectives were overall response rates (ORR), complete response rates (CRR), progression free survival (PFS), overall survival (OS), and safety. PFS and OS were estimated by Kaplan-Meier.

Results:

Patients and Treatment: We identified 65 CHL patients who received P-GVD between July 2019 and June 2024, including 43 who were treated in the second line. Enrolled patients included a median age of 31 years (range 17-69 years), 36.9% (24) females, 75.4% (49) nodular sclerosing subtype, and 60% (39) stage III-IV at diagnosis. Patients included 64.6% (42) White and non-Hispanic, 15.4% (10) Hispanic or White and Hispanic, 10.8% (7) Black, 3.1% (2) Asian/Pacific Islander, 3.1% (2) other, and 3.1% (2) unknown. The median number of prior regimens was 1 (range 0-12); these included 3.1% (2) who had prior checkpoint inhibitor (CPI), 50.8% (33) who had prior brentuximab vedotin (BV), and 3.1% (2) who had prior transplant. Patients with primary refractory disease [no initial complete response (CR)] comprised 58.5% (38), and 35.4% (23) had relapse within 1 year of completing initial therapy. The median number of cycles received was 3 (range 1-5). Treatment in a community practice setting was noted for 21.5% (14) patients.

Efficacy: At a median follow up of 17.7 months, ORR and CRR after P-GVD were 95% (62/65) and 74% (48/65), respectively. This increased to 95% ORR and 81% CRR when limited to 43 patients who were treated 2^nd line. Responses by line included: 1^st [n=1; 100% ORR and CRR]; 3^rd [n=15; 100% ORR, 73.3% CRR], 4^th [n=3; 100% ORR, 33.3% CRR], 5^th [n=2; 100% ORR, 0% CRR], and 13^th [n=1; SD]. CRR in BV- and CPI-exposed patients were 60.6% and 50%, respectively. Ninety one percent (39) of 2^nd line treated patients proceeded to autologous transplant, as well as all 3 patients > age 60. Among 41 response-evaluable second-line patients, CR was achieved in 94% (30/32) who received 2 or 3 cycles of P-GVD, and 56% (5/9) who received 4 cycles of P-GVD.

For the entire cohort at 12 and 24 months after starting P-GVD, PFS was 95% (95% CI: 89-100%), 91% (95% CI: 83-100%) and OS was 98% (95% CI: 94-100%), 94% (95% CI: 86-100%), respectively. Ninety five percent (41) of 2^nd line transplanted patients remain alive and in remission at a median of 18.5 months (range 3.5-38.7 months). In the primary refractory subset, PFS and OS at 24 months were 91% and 97%, respectively. For the cohort with 2 or more prior lines of therapy, PFS and OS at 24 months were 91% and 94%, respectively.

Safety: Immune-related adverse events (IRAEs) were reported in 20% (13) of patients, of which grade 3 IRAEs per NCCN criteria version 1.2024 comprised 38.5%; all others were grades 1-2. Non-IRAE grade 3-4 toxicities per CTCAE version 5.0 were reported in 22% (14) patients. Of 29 patients evaluable for treatment-related interruptions, 7% (2) had therapy discontinued, and 34% (10) had holds, dose reductions, and/or delays. No deaths were attributed to P-GVD treatment.

Conclusions:This retrospective study confirms the utility of P-GVD in treating relapsed/refractory CHL in a real-world population. Though fewer CRs and higher rates of grade 3 adverse events were observed, the vast majority of patients were able to proceed to transplant, and outcomes to date are highly encouraging.

Baek:Postgraduate Healthcare Education, LLC / Bristol Myers Squibb: Other: Co-presented an educational activity (continuing education) that was sponsored by Postgraduate Healthcare Education, LLC and supported by an educational grant from Bristol Myers Squibb.. Varma:Affimed NV: Current equity holder in publicly-traded company. Yamshon:Kite Pharma: Consultancy; Bristol Myers Squibb: Consultancy. Bartlett:ADC Therapeutics: Research Funding; Washington University School of Medicine: Current Employment; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Janssen: Research Funding; Kite Pharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Forty Seven: Research Funding; Celegne: Research Funding; BMS: Research Funding; Autolus: Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Foresight Diagnostics: Membership on an entity's Board of Directors or advisory committees. Shah:Incyte, Epizyme, Seattle Genetics, Loxo Oncology, Acerta: Research Funding; AbbVie, Seattle Genetics: Consultancy. Merryman:Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DG Medicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Merck: Research Funding. Svoboda:BMS: Honoraria; Merck: Honoraria; TG Therapeutics: Honoraria; Atara: Honoraria; Abbvie: Honoraria; GenMab: Honoraria; Seagen: Honoraria; Incyte: Research Funding; Adaptive: Honoraria, Research Funding. D'Angelo:Abbvie: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Genmab: Consultancy; Fate Therapeutics: Research Funding; Seagen: Consultancy; Beigene: Research Funding; Curis Inc: Consultancy, Research Funding. Advani:Gilead: Research Funding; Autolus: Honoraria, Other: DSMB/Advisory Boards; Regeneron: Research Funding; ADCT: Honoraria, Other: DSMB/Advisory Boards; Merck: Other: Steering committee, DSMB/Advisory Boards, Research Funding; BeiGene: Honoraria, Other: DSMB/Advisory Boards, Research Funding; Cyteir: Research Funding; Seattle Genetics: Research Funding; Roche/Genentech: Honoraria, Other: Steering committee, DSMB/Advisory Boards, Research Funding. Di:BeiGene: Consultancy, Research Funding; Schrodinger, Inc.: Research Funding. Lynch:SeaGen, Foresight Diagnostics, Abbvie, Janssen: Consultancy; Merck: Honoraria; TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, SeaGen, Rapt, Merck, Janssen: Research Funding. Poh:Seagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dren Bio: Research Funding; Astex: Research Funding; Acrotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shadman:Bristol Myers Squibb (spouse): Current Employment; Merck, Nurix, Fate Therapeutics, Eli Lilly, Kite Pharma, Bristol Myers Squibb: Consultancy; Morphosys/Incyte, Beigene, Genmab, AstraZeneca, Genentech, Abbvie: Consultancy, Research Funding; Koi Biotherapeutics: Current holder of stock options in a privately-held company; Vincerx, Janssen: Research Funding. Smith:Merck Sharp and Dohme Corp: Research Funding; Millenium/Takeda: Consultancy; KITE pharma: Consultancy; Karyopharm: Consultancy; Kymera Therapeutics: Research Funding; Epizyme: Consultancy; Genentech: Consultancy, Research Funding; Ignyta (spouse): Research Funding; Lumanity: Consultancy; Incyte: Consultancy, Research Funding; Enterome: Research Funding; De Novo Biopharma: Research Funding; BMS (spouse): Research Funding; Bayer: Research Funding; Coherus Biosciences (spouse): Consultancy; Beigene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC therapeutics: Consultancy, Research Funding; abbvie: Consultancy. Till:Mustang Bio: Consultancy, Patents & Royalties, Research Funding; Bristol Myers Squibb: Research Funding. Ujjani:Abbvie, Astrazeneca, Beigene, Genentech, Jansen, Lilly, Pharmacyclics: Honoraria; AbbVie, Astrazeneca, Lilly, PCYC: Research Funding. Diefenbach:FATE Therapeutics: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Millenium: Research Funding; Merck: Consultancy, Research Funding; Gilead: Current equity holder in publicly-traded company, Research Funding; Genmab: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; I MAB: Consultancy, Current equity holder in private company; NYU Grossman School of Medicine/Perlmutter Cancer Center at NYU Langone Health: Current Employment; OverT Therapeutics: Current equity holder in private company; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding. Gopal:I-Mab bio: Research Funding; Merck: Consultancy, Honoraria, Research Funding; IgM Bio: Research Funding; Takeda: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Astra Zeneca: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; SeaGen: Research Funding; Teva: Research Funding; Genmab: Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Morphosys/Incyte: Consultancy, Honoraria; ADCT: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Cellectar: Consultancy, Honoraria; Compliment: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Epizyme: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Fresenius-Kabi: Consultancy, Honoraria; Scitek: Consultancy, Honoraria; Sana: Consultancy, Honoraria.

The Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin (P-GVD) regimen has previously been studied by Moskowitz AJ, et al. J Clin Oncol 2021 and is listed as NCCN Compendium Category 2A. This study presents real-world findings with this same regimen.