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569 Pembrolizumab Maintenance Instead of Autologous Hematopoietic Cell Transplantation for Patients with Relapsed or Refractory Hodgkin Lymphoma in Complete Response after Pembrolizumab, Gemcitabine, Vinorelbine, and Liposomal Doxorubicin

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Optimization of Therapy
Hematology Disease Topics & Pathways:
Research, Clinical trials, Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Therapy sequence, Treatment Considerations, Lymphoid Malignancies
Sunday, December 8, 2024: 1:00 PM

Alison Moskowitz, MD1, Gunjan L. Shah, MD2, Nivetha Ganesan, MPH3*, Tiffany Chang, MS3*, Esther Drill, DrPH3*, Theresa Davey, MMSc, PA-C3*, Helen Hancock, ANP3*, Brittney Munayirji3*, Monifa Douglas3*, Alayna M. Santarosa, MPH3*, Ellie Casper, MS, DPT1*, Natasha Galasso3*, Sarima Subzwari3*, Marwah Jihad4*, Alexander P. Boardman, MD1*, Philip Caron, MD1, Kevin A. David, MD1*, Zachary D. Epstein-Peterson, MD1, Lorenzo Falchi, MD3, Paola Ghione, MD, MSEpi3, Paul A. Hamlin, MD1, Steven Horwitz, MD1, Andrew M. Intlekofer, MD, PhD1, William T. Johnson, DO5, Anita Kumar, MD6, Jennifer Kimberly Lue, MD1, Efrat Luttwak, MD1, Ariela Noy, MD1, Colette Owens, MD1, Maria Lia Palomba, MD1, Gilles Salles, MD, PhD7, Raphael Steiner, MD1*, Robert Stuver, MD1, Pallawi Torka, MD1, Santosha A. Vardhana, MD, PhD8, Andrew D. Zelenetz, MD, PhD1, Joachim Yahalom, MD9, Ahmet Dogan, MD, PhD3, Heiko Schoder, MD3* and Craig H. Moskowitz, MD10

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
3Memorial Sloan Kettering Cancer Center, New York, NY
4Memorial Sloan Kettering Cancer Center, NEW YORK, NY
5Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
6Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Short Hills, NJ
7Lymphoma Service Chief, Memorial Sloan Kettering Cancer Center, New York, NY
8Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
9Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
10Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL

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; Cellectar: Consultancy; Novartis: Consultancy; Bristo Meyer Squibb: Consultancy, Patents & Royalties: immediate family member. 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.

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

*signifies non-member of ASH