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459 A Randomized Phase 2 Study Incorporating Nivolumab and Brentuximab Vedotin into Radiation-Free Treatment of Early Stage Classic Hodgkin Lymphoma

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Potentially Practice-Changing Trials in Hodgkin Lymphoma
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Sunday, December 8, 2024: 10:00 AM

Ann S. LaCasce, MD, MMSc1, Deepa Jagadeesh, MD2, Hun Ju Lee, MD3, Lu Chen4*, David A. Bond, MD, BS5, Matthew Weinstock6*, Matthew Mei, MD7, Tatyana Feldman, MD8, Allison M. Winter, MD2, Jeffrey A. Barnes, MD, PhD9, Amitkumar N. Mehta, MD10, Gaurav Goyal, MD11, Sairah Ahmed, MD3, Lisa Giulino Roth, MD12, Azra Borogovac, MD13, Kristie A. Blum, MD14, Jane N Winter, MD15, Mehdi Hamadani, MD16, Sonali M. Smith, MD17, Philippe Armand, MD, PhD18, Ian W. Flinn, MD, PhD19, Jeremy S. Abramson, MD20 and Alex F. Herrera, MD4

1Dana-Farber Cancer Institute, Boston, MA
2Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
3Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
4City of Hope, Duarte, CA
5Division of Hematology, The Ohio State University, Columbus, OH
6Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA
7City of Hope Cancer Center, Duarte, CA
8John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ
9Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA
10O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
11Division of Hematology and Medical Oncology, University of Alabama at Birmingham, Birmingham, AL
12Weill Cornell Medicine, New York, NY
13Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
14Winship Cancer Institute of Emory University, Atlanta, GA
15Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
16Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
17University of Chicago, Chicago, IL
18Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
19Tennessee Oncology, Nashville, TN
20Massachusetts General Hospital Cancer Center, Boston, MA

A.S.L, D.J., and H.J.L. contributed equally

I.W.F., J.S.A., and A.F.H. contributed equally

Introduction: Maximizing treatment efficacy while minimizing late effects is critical in patients with early stage classic Hodgkin lymphoma (cHL). We hypothesized that the incorporation of brentuximab vedotin (BV) and nivolumab (nivo) in early stage cHL would improve progression-free survival and obviate the need for radiotherapy.

Methods: Patients aged 16 and older with stage IA-IIB cHL with adequate organ function without active autoimmune disease or significant neuropathy were eligible. All patients underwent PET/CT after 2 cycles of ABVD (PET2). Patients with non-bulky disease (bulky defined as > 7.5 cm on baseline PET/CT) who were PET2 negative (Deauville 1-3) were randomized to 2 additional cycles of ABVD followed by 3 months of nivo consolidation (arm A) (administered every 2 weeks) versus 3 cycles of BV-nivo administered every 3 weeks (arm B1), in both cases without radiation. Patients were stratified for baseline factors of stage I vs II and A vs B symptoms. PET-2 negative patients with bulky disease received 2 additional cycles of ABVD followed by 3 months of nivo consolidation (arm B2). PET2 positive patients received BV-AVD for 4 cycles followed by PET-CT and, if in CR, went on to receive 3 months of nivo consolidation (arm C). The primary endpoint was 18-month progression free survival.

Results: 153 patients were evaluable with median age of 31 years (18-73). 78 (51%) were male, 117 (76%) were white, 8 (5%) were black, 10 (7%) were Asian, 4 (3%) were other or mixed race, and 14 (9%) were unknown/not-disclosed.19 (12%) were Hispanic. 142 (93%) patients had nodular sclerosis or NOS subtype. 23 (15%) had extranodal disease. 134 (88%) had stage II disease, and 50 (33%) had B symptoms. According to GHSG, 54 (35%) were favorable and 95 (62%) unfavorable (3% missing information). 52 (34%) patients had bulky disease. 75% of patients were PET2 negative after 2 cycles of ABVD. Assignment to arms was: Arm A 45 (29%), Arm B1 36 (24%), Arm B2 35 (23%) and Arm C 37 (24%). The median follow-up was 22 months across study arms. The 18m PFS for Arm A and Arm B1 (non-bulky PET2-negative) was 100%, 97% (95% CI 81%-99.6%) for Arm B2 (bulky PET2 negative), and 81% (62%-91%) for Arm C (PET2 positive). The 24m PFS for Arm A and Arm B1 was 100%, 86% (66%-94%) for Arm B2, and 76% (55%-88%) for Arm C. No deaths have been reported to date in any study arm.

The most common adverse events (AEs) of any grade in patients treated on Arm A (BV+Nivo) were: maculopapular rash (40%), infusion related reaction (24%), nausea (22%), and peripheral sensory neuropathy (20%). The most common AEs in Arm B1/B2 were: neutropenia (48%), nausea (35%), fatigue (35%), constipation (24%), ALT elevation (21%), anemia (20%), and peripheral sensory neuropathy (20%). The most common AEs in Arm C were: peripheral sensory neuropathy (70%), constipation (54%), nausea (49%), fatigue (49%), neutropenia (46%), anemia (38%), vomiting (35%), diarrhea (32%). Febrile neutropenia occurred in 0% of Arm A patients, 7% of Arm B patients, and 8% of Arm C patients. 4 patients in arm A, 7 in arm B and 1 in arm C discontinued therapy for toxicity.

Conclusion: Incorporating Nivo +/- BV without radiotherapy in PET2-negative cHL patients with non-bulky early stage cHL after 2 cycles of ABVD resulted in 24-month PFS of 100% with manageable toxicity. PET2-negative patients with bulky disease and PET2-positive patients experienced good disease control, although alternative approaches for bulky PET2-negative patients and continued use of radiation in PET2 positive patients may be warranted. These results support the ongoing PET-adapted US Children’s Oncology Group led Intergroup study AHOD2131 comparing standard therapy to the incorporation of BV-nivo in early stage cHL.

Disclosures: LaCasce: Genmab: Consultancy, Honoraria. Jagadeesh: AstraZeneca, ATARA Biotherapeutics, Debio Pharma, LOXO Pharmaceuticals, MEI Pharma, Regeneron Pharmaceuticals, Inc., Seagen, Trillium Pharmaceuticals: Research Funding; Affimed, Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Lee: AstraZeneca: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Oncternal: Consultancy, Research Funding; BMS: Research Funding; Curio: Honoraria; MJH: Honoraria. Bond: GenMab: Research Funding; ADC Therapeutics: Consultancy; AstraZeneca: Research Funding; Accutar: Research Funding; Nurix Therapeutics: Consultancy, Research Funding; BMS: Research Funding; Kite/Gilead: Research Funding; Incyte: Research Funding; Novartis: Consultancy, Research Funding. Mei: Novartis: Consultancy; Synethkine: Consultancy; SeaGen: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; BMS: Research Funding; Incyte: Research Funding; Beigene: Research Funding; Genentech: Research Funding. Feldman: Epizyme: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Alexion: Research Funding; Pharmacyclics: Consultancy, Honoraria; Merck: Research Funding; TESSA: Research Funding; Portola: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; DAIICHI: Research Funding; Genmab: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding; Astrazeneca: Consultancy, Honoraria, Research Funding; Kymera: Research Funding; Corvus: Research Funding; ADCT: Consultancy, Honoraria, Research Funding; OMI: Current equity holder in private company; Genomic Testing Cooperative: Current equity holder in private company; Trillium: Research Funding. Winter: BeiGene: Consultancy; BTG Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy. Goyal: Opna Bio, Seagen: Membership on an entity's Board of Directors or advisory committees; Recordati: Consultancy. Ahmed: Merck: Research Funding; Nektar: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; Janssen: Research Funding; Xencor: Research Funding; ADC Therapeutics: Consultancy. Roth: Roche: Consultancy; Merck: Consultancy. Borogovac: Janssen: Membership on an entity's Board of Directors or advisory committees. Winter: Merck: Consultancy, Research Funding; BMS: Consultancy; Genetech: Consultancy. Hamadani: Caribou: Consultancy; Genentech: Speakers Bureau; Takeda: Research Funding; Myeloid Therapeutics: Speakers Bureau; AbbVie: Consultancy; Sanofi Genzyme: Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Forte Biosciences: Consultancy; Allovir: Consultancy; CRISPR: Consultancy; Autolus: Consultancy; Genmab: Consultancy; BMS: Consultancy; Omeros: Consultancy; Astellas Pharma: Research Funding; Kite Pharma: Consultancy, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau. Smith: Caris Life Sciences: Other: Spouse is employed by Caris Life Sciences; Ono Pharmaceutical: Consultancy; Genmab: Consultancy; Regeneron: Other: Educational lecture. Armand: Merck: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Genmab: Consultancy; Enterome: Consultancy; Genentech/Roche: Consultancy, Research Funding; ATB Therapeutics: Consultancy; Foresight: Consultancy; Regeneron: Consultancy; Kite: Research Funding; Adaptive: Research Funding; IGM: Research Funding; AstraZeneca: Research Funding. Flinn: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Genentech: Consultancy; Genmab: Consultancy; Kite, a Gilead Company: Consultancy; Roche: Consultancy; Vincerx: Consultancy; Acerta: Research Funding; Agios: Research Funding; ArQule: Research Funding; AstraZeneca: Research Funding; BioPath: Research Funding; BMS: Research Funding; CALIBR: Research Funding; CALGB: Research Funding; Celgene: Research Funding; City of Hope Medical Center: Research Funding; Constellation Pharmaceuticals: Research Funding; Curis: Research Funding; CTI: Research Funding; Biopharma: Research Funding; Epizyme: Research Funding; Fate Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Gilead Sciences: Research Funding; InnoCare Pharma: Research Funding; IGM Biosciences: Research Funding; Incyte: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Loxo: Research Funding; Marker Therapeutics: Research Funding; Merck: Research Funding; Millennium Pharmaceuticals: Research Funding; MorphoSys: Research Funding; Myeloid Therapeutics: Research Funding; Novartis: Research Funding; Nurix: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Portola Pharmaceuticals: Research Funding; Rhizen Pharmaceuticals: Research Funding; Roche: Research Funding; Seattle Genetics: Research Funding; Step Pharma: Research Funding; Tessa Therapeutics: Research Funding; TG Therapeutics: Research Funding; Vincerx Pharma, 2seventybio: Research Funding; Vincerx Advisory Committee: Membership on an entity's Board of Directors or advisory committees; Tennessee Oncology & OneOncology: Current Employment. Abramson: BeiGene Ltd: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy; Genentech, a member of the Roche Group: Consultancy; Genmab US Inc: Consultancy; Incyte Corporation: Consultancy; Interius BioTh: Consultancy; Seagen Inc.: Research Funding; Mustang Bio: Research Funding; Merck: Research Funding; Cellectis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AbbVie Inc: Consultancy; Caribou Biosciences Inc: Consultancy; Century Therapeutics: Consultancy; Epizyme Inc: Consultancy; Foresight Diagnostics: Consultancy. Herrera: Tubulis: Consultancy; AstraZeneca: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Adicet Bio: Consultancy; Merck: Consultancy, Research Funding; Genmab: Consultancy; KiTE Pharma: Research Funding; Gilead Sciences: Research Funding; AbbVie: Consultancy; Pfizer: Consultancy; Regeneron: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Caribou Biosciences: Consultancy; Allogene Therapeutics: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy.

*signifies non-member of ASH