Introduction: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (HL) following front-line treatment failure is second line therapy (SLT) aimed to achieve complete response (CR), followed by consolidation with high dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). We previously reported results from Part I of our phase II study evaluating SLT with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD) followed by HDT/AHCT (Moskowitz, et al. JCO 2021) in which 95% of patients achieved CR and 96% are progression-free at 30 months. Building upon the excellent results observed with P-GVD, we next explored whether patients achieving CR after P-GVD could avoid HDT/AHCT.

Methods: Part II of the P-GVD study enrolled patients with RR HL following 1 line of therapy. Patients received 4 cycles of P-GVD and those who achieved CR proceeded to 13 cycles of pembrolizumab maintenance (200mg IV every 21 days). The primary endpoint was 2-year progression free survival (PFS) after start of maintenance. Our hypothesis was that this treatment would lead to a 2-year PFS of 75% but no less than 50%, thus we aimed to initiate pembrolizumab maintenance in 23 patients who achieved CR after P-GVD to ensure a power of 80% and significance of 0.05.

Results: Among 40 patients enrolled, median age was 36 (range 19-76), 18 (45%) were male, 17 (43%) had primary refractory disease, 18 (45%) had extranodal disease, 16 (40%) had stage IV disease, and 7 (18%) had B symptoms at enrollment. All pts responded to P-GVD, including 36 (90%) with CR and 4 (10%) with PR. Of 36 pts with CR, 5 elected to proceed to AHCT, 4 were referred to AHCT by treating physician due to treatment-related toxicity (1 pt with G4 immune thrombocytopenia and G2 pneumonitis; 1 with G1 pneumonitis, 1 with G2 rash, 1 with G3 PJP pneumonia), 2 elected to come off study and receive no further treatment, and 1 died from pneumonitis following 4 cycles of P-GVD before proceeding to maintenance. Among 24 pts who proceeded to maintenance, 10 experienced progression of HL either during pembrolizumab maintenance (n=3), 3-6 months after completion of pembrolizumab maintenance (n=4), or > 10 months from completion of pembrolizumab maintenance (n=3).

After a median follow-up of 23.4 mos, 2-year PFS was 51% (95% CI 33-80). Stage IV disease at enrollment was significant for higher risk of progression (PFS 18% vs 69%, p=0.03). Nine of the 10 pts who progressed successfully proceeded with AHCT and remain in remission after a median of 12.7 months (range: 3.8-24.4) post-transplant. One patient with progression was not eligible for transplant due to comorbidities and is receiving palliative treatment with pembrolizumab plus gemcitabine.

Conclusion: After a median follow-up of 23.4 mos after maintenance, 51% of pts with RR HL treated with P-GVD followed by maintenance were progression free. Furthermore, pts who relapsed during or after maintenance were salvaged with third-line therapy and AHCT. Patients with stage IV disease are more likely to need AHCT. A randomized study evaluating AHCT versus pembrolizumab maintenance for patients with RR stage I-III HL who achieve CR to P-GVD is underway.

Disclosures

Moskowitz:Secura Bio: Research Funding; Takeda Therapeutics: Honoraria; ADC therapeutics: Research Funding; Tessa Therapeutics: Honoraria; Miragen Therapeutics: Honoraria; Seattle Genetics: Honoraria, Research Funding; Merck: Research Funding; Incyte: Research Funding; Brystal-Meyers Squibb: Research Funding; Beigene: Research Funding. Shah:Janssen, Amgen, Beyond Spring, BMS, GPCR, DSMB with ArcellX.: Research Funding. Boardman:Bristol Myers Squibb: Consultancy; OncLive: Honoraria; Cancer Study Group, LLC: Consultancy. Epstein-Peterson:Genmab: Consultancy; Amgen: Research Funding; Kymera: Research Funding; OncLive: Honoraria; Viracta: Research Funding. Falchi:Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees; Taylor Francis: Other: Journal Editor; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; Genmab: Consultancy, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; EvolveImmune: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kaplan: Other: CME Presentation: Projects in Knowledge. Horwitz:Auxilius Pharma, Abcuro Inc., Corvus, Daiichi Sankyo, DrenBio, Farallon Capital Management, L.L.C., Kyowa Hakko Kirin, March Bio, Neovii Pharmaceuticals AG, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio, Treeline Bio and Takeda Pharmaceuticals.: Consultancy; ADC Therapeutics, Affimed, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio.: Research Funding; Auxilius Pharma, Abcuro Inc., Corvus, CTI BioPharma Corp, Daiichi Sankyo, DrenBio, Kyowa Hakko Kirin, March Bio, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio and Takeda Pharmaceuticals.: Honoraria. Johnson:BioNTech: Consultancy; Sobi: Other: Advisory Board; Electra Therapeutics: Other: Advisory Board. Kumar:Seattle Genetics: Research Funding; Loxo Oncology/Lily Pharmaceuticals: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; BridgeBio Pharmaceuticals: Current equity holder in publicly-traded company; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals, Janssen: Honoraria; Adaptive Biotechnologies, Celgene, Pharmacyclics: Research Funding; Abbvie Pharmaceuticals: Research Funding. Lue:Kymera Therapeutics: Research Funding; ADC Therapeutics: Consultancy; GenMab: Consultancy; Merck Pharmaceuticals: Consultancy; Lumanity: Consultancy. Noy:janssen Global: Consultancy, Other: drug provided for research; health advance: Consultancy; clearview: Consultancy; OncLIve: Honoraria; ADC therapeutics: Consultancy; guidepoint global: Consultancy; Medallion Healthcare: Honoraria; Beigene: Consultancy; epizyme: Consultancy; Cornerstone Pharma: Honoraria, Research Funding; PER: Honoraria; EUSA: Consultancy; AstraZeneca: Consultancy; NSCI: Honoraria. Palomba:Synthekine: Consultancy; Novartis: Consultancy; Bristo Meyer Squibb: Consultancy; Cellectar: Consultancy. Salles:Genentech/Roche: Consultancy, Research Funding; BMS/Celgene: Consultancy; Merck: Consultancy; AbbVie: Consultancy, Research Funding; Kite/Gilead: Consultancy; BeiGene: Consultancy; Ipsen: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Molecular Partners: Consultancy; Janssen: Consultancy, Research Funding; Incyte: Consultancy; Nurix: Research Funding. Steiner:Rafael Pharmaceuticals: Research Funding; Seagen: Research Funding; BMS: Research Funding; GSK: Research Funding; NCI CTEP: Research Funding. Stuver:Pfizer: Research Funding. Torka:Abbvie: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Genentech: Consultancy; Genmab: Consultancy; Seagen: Consultancy; Lilly Oncology: Consultancy. Zelenetz:BeiGene: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Genentech/Roche: Consultancy, Research Funding; Gilead/Kite: Consultancy; Adaptive Biotechnology: Consultancy; BMS/Celgene/Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; AstraZeneca: Consultancy; MEI Pharma: Consultancy, Research Funding; MorphoSys: Consultancy. Yahalom:Convergent RNR: Consultancy. Dogan:AstraZeneca: Research Funding. Moskowitz:ADCT: Research Funding; Merk: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; SGEN: Research Funding.

Off Label Disclosure:

Pembrolizumab combined with chemotherapy as second line therapy for Hodgkin lymphoma.

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2024
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