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Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Potentially Practice-Changing Trials in Hodgkin Lymphoma
Hematology Disease Topics & Pathways:
Research, Clinical trials, Hodgkin lymphoma, Combination therapy, Adult, Lymphomas, Clinical Research, Diseases, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved for patients with advanced classical Hodgkin lymphoma (cHL). A study in nonbulky early-stage cHL showed preserved efficacy with improved safety when omitting vinblastine in the BV+AD regimen (Blood Adv. 2023;7[7]:1130-1136). Initial results from the phase 2 SGN35-027 part C study, with a median follow-up of 16.5 months, showed promising efficacy and an acceptable safety profile for BV and nivolumab in combination with chemotherapy (AN+AD) in patients with nonbulky, early-stage cHL. Here, we present updated results from this study after longer follow-up.
Methods
SGN35-027 (NCT03646123) part C enrolled patients with Ann Arbor stage I or II cHL without bulky disease, defined as those with a single node or nodal mass with a <10-cm diameter on computed tomography. Patients received 4 cycles of AN+AD (BV 1.2 mg/kg [A] capped at 100 kg, nivolumab 240 mg [N], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]) intravenously on days 1 and 15 of each 28-day cycle. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was not required. The primary endpoint is complete response (CR) rate at end of treatment (EOT) by investigator assessment per Lugano 2014 classification with incorporation of LYRIC. Secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), duration of CR (DOCR), and safety analysis. Additional analyses included efficacy assessments for early favorable and early unfavorable subgroups, as defined per German Hodgkin Study Group criteria.
Results
At the data cutoff of May 30, 2024, 154 patients received ≥1 dose of AN+AD (male, 45%; female, 55%; White, 84%; early favorable, 36%; early unfavorable, 64%; median age, 31 years [range, 18-77 years]). The median duration of follow-up was 30.7 months (range, 24-45 months). The ORR at EOT was 96% (95% CI, 92%-99%), and the CR rate was 92% (95% CI, 86%-95%). In the early favorable (n=55) and early unfavorable (n=98) subgroups, CR rates were 95% (95% CI, 85%-99%) and 91% (95% CI, 83%-96%), respectively. Of patients who achieved a CR, the DOCR rate at 36 months was 95% (95% CI, 89%-98%). At a median PFS follow-up of 26.3 months, 6 patients (4%) had progressive disease, all of whom had early unfavorable disease at diagnosis. No progressive disease events were reported in early favorable patients. The 36-month PFS rate was 95% (95% CI, 88%-98%). The planned treatment course of 4 cycles was completed by 98% of patients. Six patients (4%) received subsequent treatment; of them, 2 received consolidative radiotherapy. Overall, 44% of patients received G-CSF at investigator discretion, mostly for primary prophylaxis.
Any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Grade ≥3 treatment-related TEAEs occurred in 34% of patients, most commonly neutropenia (9%), alanine aminotransferase (ALT) increase (7%), aspartate aminotransferase increase (5%), lipase increase (3%), and peripheral sensory neuropathy (3%). Any-grade treatment-emergent immune-mediated adverse events (IMAEs) with a potential immunologic cause occurred in 22% of patients, most commonly hypothyroidism (6%), hyperthyroidism (5%), maculopapular rash (4%), ALT increase (3%), and pneumonitis (2%). Grade ≥3 treatment-emergent IMAEs occurred in 8% of patients, most commonly ALT increase (3%) and maculopapular rash (1%). Serious TEAEs occurred in 19% of patients. Treatment-related serious TEAEs occurred in 12% of patients, with the most common being pyrexia (3%). There was 1 disease-related death reported after the safety reporting period.
Conclusions
This updated analysis from the SGN35-027 part C study demonstrated continued efficacy of this novel regimen, sparing bleomycin, vinblastine, and radiation, in early-stage cHL, with a CR rate of 92% and 36-month PFS rate of 95%. The safety profile remains favorable and consistent with that in the prior analysis. Long-term results from this study support the use of BV and nivolumab in combination with limited chemotherapy in patients with nonbulky, early-stage cHL.
Disclosures: Abramson: Merck: Research Funding; Cellectis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AbbVie Inc: Consultancy; Interius BioTh: Consultancy; Incyte Corporation: Consultancy; Genmab US Inc: Consultancy; Genentech, a member of the Roche Group: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy; BeiGene Ltd: Consultancy; Caribou Biosciences Inc: Consultancy; Century Therapeutics: Consultancy; Epizyme Inc: Consultancy; Foresight Diagnostics: Consultancy; Mustang Bio: Research Funding; Seagen Inc.: Research Funding. Bartlett: Foresight Diagnostics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Millennium: Research Funding; Celegne: Research Funding; Forty Seven: Research Funding; Kite Pharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Washington University School of Medicine: Current Employment; ADC Therapeutics: Research Funding; Gilead: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding; Autolus: Research Funding; BMS: Research Funding. Burke: Genentech/Roche: Consultancy; Kymera: Consultancy; Adaptive Biotechnologies: Consultancy; Abbvie: Consultancy; SeaGen: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Regeneron: Consultancy; BeiGene: Consultancy; Foresight Diagnostics: Consultancy; Nurix: Consultancy; Eli Lilly and Company: Honoraria, Other: Food/Beverage ; Genmab: Consultancy; AstraZeneca: Consultancy. Lynch: SeaGen, Foresight Diagnostics, Abbvie, Janssen: Consultancy; TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, SeaGen, Rapt, Merck, Janssen: Research Funding; Merck: Honoraria. Domingo Domenech: Bristol Myers Squibb-Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ideogen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Linhares: Kyowa Kirin: Speakers Bureau; Pfizer, ADC, Abbvie, Novartis, BeiGene, BMS, Kyowa, Genentech, AstraZeneca, Kite, Janssen: Other: Advisory boards; Baptist Health South Florida: Current Employment; Institutional PI on SGN35-027 Part C trial with corresponding research funding by Seagen/Pfizer: Research Funding. Ramchandren: Pfizer BMS (institutional): Research Funding. Gandhi: Janssen Oncology Ad Board 5/2023: Membership on an entity's Board of Directors or advisory committees; Sanofi Ad Board 12/2022: Membership on an entity's Board of Directors or advisory committees. Shah: AbbVie, Seattle Genetics: Consultancy; Incyte, Epizyme, Seattle Genetics, Loxo Oncology, Acerta: Research Funding. Jurczak: Roche: Consultancy, Research Funding; Merck: Research Funding; Lilly: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; MSD: Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Re: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Sobi: Speakers Bureau. Prince: Takeda: Honoraria; Bristol Myers Squibb: Honoraria; GSK: Honoraria; Amgen: Honoraria; Johnson and Johnson: Honoraria; AbbVie: Research Funding; Mallinckrodt: Honoraria; Kyowa Kirin: Honoraria. Guo: Seagen, Pfizer: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Pfizer: Current Employment, Current equity holder in publicly-traded company. Davis: Seagen, a wholly owned subsidiary of Pfizer, Inc.; Bristol Myers Squibb: Research Funding; Pfizer, Inc.: Current equity holder in publicly-traded company; Seagen, a wholly owned subsidiary of Pfizer, Inc.: Ended employment in the past 24 months; Pfizer, Inc.: Current Employment. Ho: Pfizer Inc.: Current Employment. Yasenchak: Pfizer: Consultancy; Beigene: Speakers Bureau. Lee: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Oncternal: Consultancy, Research Funding; Takeda: Research Funding; Curio: Honoraria; MJH: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding.
OffLabel Disclosure: Brentuximab with nivolumab in combination with limited chemotherapy is not approved in patients with nonbulky, early-stage classical Hodgkin lymphoma. The SGN35-027 part C study is exploring this combination in this specific patient population.