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181 Nivolumab-AVD Is Better Tolerated and Improves Progression-Free Survival Compared to Bv-AVD in Older Patients (Aged ≥60 Years) with Advanced Stage Hodgkin Lymphoma Enrolled on SWOG S1826Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK Cell Lymphomas: Clinical and Epidemiological: Topics in T Cell, Szary and Hodgkin Lymphomas
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Clinical Research, Combination therapy, Checkpoint Inhibitor, Therapies, Monoclonal Antibody Therapy
Saturday, December 9, 2023: 2:00 PM

Sarah C. Rutherford, MD1, Hongli Li, MS2*, Alex F. Herrera, MD3, Michael Leblanc2*, Sairah Ahmed, MD4, Kelly L. Davison, MD, PhD5*, Carla Casulo, MD6, Nancy L. Bartlett, MD7, Joseph M Tuscano, MD8, Brian Hess, MD9, Pallawi Torka, MD10, Pankaj Kumar, MD11, Ryan W Jacobs, MD12, Joo Y Song, MD13, Sharon M. Castellino, MD, MSc14, Brad S. Kahl, MD15, John P. Leonard1, Sonali M. Smith16, Jonathan W. Friedberg, MD, MMSc6 and Andrew M Evens, DO, MBA, MMSc17

1Weill Cornell Medicine, New York, NY
2Fred Hutchinson Cancer Center, Seattle, WA
3City of Hope, Duarte, CA
4Department of Lymphoma/Myeloma and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX
5Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, CAN
6Wilmot Cancer Center, University of Rochester, Rochester, NY
7Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO
8University of California, Davis Medical Center, Sacramento, CA
9Medical University of South Carolina, Charleston, SC
10Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
11Illinois CancerCare, Bloomington, IL
12Atrium Health Levine Cancer Institute, Charlotte, NC
13City of Hope National Medical Center, Duarte, CA
14Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
15Siteman Cancer Center, Division of Oncology, Washington University School of Medicine in St. Louis, Saint Louis, MO
16Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
17Division of Blood Disorders, Rutgers Cancer Institute New Jersey, New Brunswick, NJ

Background: Survival rates in patients (pts) with classic Hodgkin lymphoma (HL) aged ≥60 years (y) are lower than younger pts. The difference is due to comorbidities, impaired performance status, decreased chemotherapy tolerance, and increased treatment-related toxicity and mortality. The frontline regimen Bv-AVD can be challenging to administer in older patients due to toxicities, particularly infection and neuropathy. The PD-1 pathway is central to pathogenesis of HL; PD-1 blockade is effective in HL. The randomized, phase 3 trial, S1826, was conducted by the National Clinical Trials Network to evaluate N-AVD vs Bv-AVD in pts with newly diagnosed advanced stage (AS) HL and enrolled 994 pts; 97 were eligible and aged ≥60y.

Methods: In this subset analysis, eligible pts were ≥60y with stage 3-4 HL. Pts were randomized 1:1 to 6 cycles of N-AVD or Bv-AVD. G-CSF neutropenia prophylaxis was optional with N-AVD and required with Bv-AVD. Pre-specified pts could receive radiation therapy (RT) to residual lesions on end of treatment PET. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. Response and progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), event-free survival (EFS), and detailed toxicity and safety events. EFS events were death without progression, progression/relapse, receipt of non-protocol systemic anti-lymphoma therapy without progression, or receipt of RT in a pt not declared eligible for RT at registration or who did not meet protocol-specified criteria for RT.

Results: 97 pts aged ≥60y were enrolled from 7/9/19-10/5/22 and were randomized to N-AVD (n=48) or Bv-AVD (n=49). Median age was 66y (range, 60-83y), 62% were male, 86% were white, 3% were black, and 10% were Hispanic. 61% had stage IV disease and 47% had IPS 4-7. 69% of pts on N-AVD and 92% of pts on Bv-AVD received any G-CSF. No pts received RT per protocol.

95 pts were evaluable for safety analysis. While grade (gr) ≥3 hematologic toxicity occurred in 52% of pts on N-AVD and 38% on Bv-AVD (gr 3 neutropenia 48% vs 30%), febrile neutropenia, sepsis, and infections were lower for pts who received N-AVD vs Bv-AVD. (Table) Peripheral neuropathy was much less frequent with N-AVD than Bv-AVD in overall incidence (sensory: 31% vs 66% and motor: 8% vs 15%, respectively) and severity (grades ≥2, sensory: 10% vs 49% and motor: 0% vs 8%, respectively). (Table) The following adverse events, AEs (mainly <gr 3) were less frequent on N-AVD vs Bv-AVD: nausea (38% vs 62%), diarrhea (25% vs 45%), anorexia (15% vs 38%) and weight loss (4% vs 36%). Hypothyroidism (15% vs 0%), and rash (16% vs 2%, no gr ≥3) were more frequent on N-AVD than Bv-AVD; rates of other immune-related toxicities were similar between arms.

In this subset analysis, median follow-up 12.1 months, PFS was superior in the N-AVD arm [HR 0.35 (95% CI 0.12-1.02) stratified one-sided logrank p=0.022]; 1-yr PFS was 93% (95% CI 79-98%) for N-AVD and 64% (95% CI 45-77%) for Bv-AVD. (Figure) 1-yr EFS was 93% (95% CI 79-98%) for N-AVD and 57% for Bv-AVD (95% CI 38-72%) [HR 0.19 (95% CI 0.06-0.61) stratified one-sided logrank p=0.0011]. 1-yr OS was 95% (95% CI 83-99%) for N-AVD and 83% (95% CI 67-92%) for Bv-AVD [HR 0.35 (95% CI 0.07-1.75) stratified one-sided logrank p=0.091]. On N-AVD, there were 2 deaths (due to infection/sepsis) and 3 progressions/relapses; on Bv-AVD, there were 7 deaths (5 due to infection/sepsis, 1 to pneumonitis, 1 unknown) and 8 progressions/relapses. Non-relapse mortality was 4% for N-AVD vs 14% for Bv-AVD. Treatment was discontinued early in 5 pts (10%) on N-AVD and 16 pts (33%) on Bv-AVD. N was discontinued early in 7 pts (15%) and Bv in 19 pts (39%). Reasons for discontinuation included (N vs Bv): AE (5 vs 14 pts), death (1 vs 3 pts), and disease progression (0 vs 1 pt).

Conclusions: N-AVD improved PFS and EFS, and was better tolerated than Bv-AVD in pts aged ≥60 with AS HL. Substantially more pts discontinued Bv-AVD than N-AVD, primarily due to toxicity. Fewer deaths occurred on N-AVD than Bv-AVD. N-AVD is poised to become a standard of care for older AS HL pts fit for anthracycline-based combination therapy.

Funding provided by the National Cancer Institute of the National Institutes of Health CA180888, CA180819, CA180821, CA180820, CA180863, CA189955 and funding/drug provided by BMS, drug provided by SeaGen for pts enrolled in Canada.

Disclosures: Rutherford: Constellation: Research Funding; Genentech: Research Funding; Genmab: Consultancy; Karyopharm: Consultancy, Research Funding; Kite: Consultancy; Seagen: Consultancy; ADC Therapeutics: Consultancy; BMS: Consultancy. Herrera: Regeneron: Consultancy; Caribou Biosciences: Consultancy; BMS: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding; Genmab: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Allogene Therapeutics: Consultancy; Tubulis GmbH: Consultancy; Merck: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding; AbbVie: Consultancy; Adicet Bio: Consultancy; AstraZeneca/MedImmune: Consultancy; Karyopharm Therapeutics: Consultancy; Gilead Sciences: Research Funding; AstraZeneca: Research Funding. Ahmed: ADC Therapeutics: Consultancy; Servier: Consultancy; Kite/Gilead: Consultancy; Chimagen: Research Funding; Genmab: Research Funding; Merck: Research Funding; Janssen: Research Funding. Davison: Abbvie: Consultancy; Beigene: Consultancy; BMS: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Kite/Gilead: Consultancy; Novartis: Consultancy; Roche: Consultancy; Seagen: Consultancy. Casulo: SecuraBio: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Verastem: Research Funding; Abbvie: Consultancy; Follicular Lymphoma Foundation: Other: Leadership role; GenMab: Research Funding; Gilead Sciences: Research Funding; Lymphoma Research Foundation: Other: Leadership Role; Genentech: Consultancy, Research Funding. Bartlett: ADC Therapeutics, Genentech, a member of the Roche Group, Seagen Inc: Other: Advisory Committee; ADC Therapeutics, Autolus, Bristol-Myers Squibb Company, Celgene Corporation, Forty Seven Inc, Immune Design, Janssen Biotech Inc, Kite, A Gilead Company, Merck, Pharmacyclics LLC, an AbbVie Company, Genentech, a member of the Roche Group, Seagen Inc, Tak: Other: Contracted Research; Foresight Diagnostics: Other: Advisory Board; Kite: Other: Advisory Board; Millinneum: Research Funding. Hess: ADC Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy. Torka: TG Therapeutics: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy; Lilly USA: Consultancy; Genmab: Consultancy; Seagen: Consultancy. Jacobs: Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; SecuraBio: Consultancy, Speakers Bureau; AbbVie: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teneobio: Research Funding; Beigene: Consultancy, Speakers Bureau; Adaptive: Consultancy; AstraZeneca: Research Funding, Speakers Bureau; LOXO Oncology: Research Funding. Castellino: SeaGen Inc.: Other: Scientific Advisory Committee - No honoraria, Research Funding; Bristol Meyers Squibb: Honoraria, Other: Scientific Advisory Committee. Leonard: National Cancer Institute, Leukemia and Lymphoma Society, Genentech, Epizyme, Janssen: Research Funding; AbbVie, AstraZeneca, Astellas, Bayer, BeiGene, BMS, Calithera, Constellation, Eisai, Epizyme, GenMab, Grail, Incyte, Janssen, Karyopharm, Lilly, Merck, Mustang Bio, Pfizer, Roche/Genentech, Seagen, Second Genome, Sutro: Consultancy. Smith: Bristol-Myers Squibb, Gilead, Ono Pharmaceutical: Consultancy, Speakers Bureau. Evens: Seattle Genetics: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

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