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471 Frontline Brentuximab Vedotin As Monotherapy or in Combination for Older Hodgkin Lymphoma Patients

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Clinical Studies in Hodgkin Lymphoma
Hematology Disease Topics & Pathways:
Biological, antibodies, Diseases, Hodgkin Lymphoma, Therapies, T-Cell Lymphoma, Lymphoid Malignancies
Sunday, December 6, 2020: 2:15 PM

Christopher A. Yasenchak, MD1, Rodolfo Bordoni, MD2*, Dipti Patel-Donnelly, MD3, Timothy Larson, MD4*, Jerome Goldschmidt, MD5*, Ralph V. Boccia, MD6, Vivian J.M. Cline7*, Mariana Sacchi, MD8*, Andres Forero-Torres9*, Robert B. Sims, MD9, Jingmin Liu9* and Jonathan W. Friedberg, MD, MSSc10

1Willamette Valley Cancer Institute and Research Center, Eugene, OR
2Georgia Cancer Specialists, Marietta, GA
3Virginia Cancer Specialists, Fairfax, VA
4Minnesota Oncology P.A., Minneapolis, MN
5Oncology and Hematology Associates of SW Virginia, Blackburgs, VA
6Center for Cancer and Blood Disorders, Bethesda, MD
7U.S. Oncology Associates, Austin, TX
8Bristol-Myers Squibb Company, Princeton, NJ
9Seattle Genetics, Inc., Bothell, WA
10University of Rochester Medical Center, Rochester, NY

Introduction: Older patients with classical Hodgkin lymphoma (cHL) have poor outcomes relative to younger patients, often due to comorbidities and toxicities related to standard first‑line (1L) chemotherapy (5-yr PFS: 30%–45% vs 75%–80%) (Evens 2008; Proctor 2009). Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, has robust activity in patients refractory to several lines of chemotherapy.

Methods: This phase 2, open-label study, SGN35-015 (NCT01716806), evaluated efficacy and tolerability of BV alone or combined with single-agents in treatment-naive cHL patients ≥60 yr. The full-analysis set (FAS) includes all patients who received BV (1.8 mg/kg IV). Patients in Part A received BV monotherapy on Day 1 of every 3-week cycle (n=26); Part B: BV+dacarbazine (DTIC; 375 mg/m2; n=19); Part C: BV+bendamustine (benda; 70 mg/m2; n=20); and Part D: BV+nivolumab (nivo; 3 mg/kg; n=20). The efficacy evaluable (EE) set includes FAS who had at least 1 post-baseline response assessment (n=25, 19, 17, 19).

Results: Demographic characteristics were generally similar: median age 78, 69, 75, and 72 yr in Parts A, B, C, and D, respectively, and 62% of patients (range 45%–70%) reported impaired physical functioning at baseline. Most patients had disease stage III/IV (62%, 68%, 75%, 80%), were ECOG 0/1 (77%, 74%, 80%, 95%), and male (54%, 68%, 50%, 75%). Median time from diagnosis was 1.2 to 1.5 mo (FAS; 10 Jan 2020 data cutoff). ORR were high (92% [95% CI: 74%, 99%], 100% [95% CI: 82.4%, 100%], 100% [95% CI: 80.5%, 100%], 95% [95% CI: 74%, 99.9%]) at a median follow-up of 59.4, 58.6, 51.3, and 19.4 mo in the EE data set. Median PFS in the EE set was 10.5 mo (95% CI: 5.6, 77.5) with monotherapy and 46.8 mo (95% CI: 11.0, 68.7), 40.3 mo (95% CI: 4.8, NR), and not reached (95% CI: 9.4, NR) in the combination parts. Median OS in the FAS set was 77.5 mo (95% CI: 40.1, NR) with monotherapy; 64.0 (95% CI: 53.4, NR), 46.9 (95% CI: 6.8, NR), and not reached (95% CI: NR, NR) in the combination parts. Treatment-related adverse event (AE) ≥ Grade 3 occurred in 50%, 37%, 70%, and 60% of patients; peripheral neuropathy (PN) was most common (35%, 26%, 20%, 35%). Treatment-related serious AEs occurred in 12%, 11%, 40%, and 5% of patients. Part C enrollment (BV+benda) closed early due to multiple acute toxicities. There were no treatment-related deaths in any part of the study. The median treatment cycles per patient were 8.0, 12.0, 5.0, and 14.5. Treatment discontinuation due to related AEs occurred in 42%, 42%, 40%, and 30% of patients, most commonly due to PN (38%, 37%, 30%, 20%).

Conclusions: Older patients with cHL and multiple comorbidities have very high response rates and a clinically meaningful improvement in PFS with BV as monotherapy or combined with other single agents and improved tolerability versus combination chemotherapy. Median overall survival exceeded 6 yrs with BV monotherapy. BV+nivo or BV+DTIC appeared to be the most reasonable combination treatment options in this study.

Disclosures: Yasenchak: BeiGene: Speakers Bureau; Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria. Bordoni: Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Guardant Health: Honoraria, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Patents & Royalties; Northside Hospital Cancer Institute: Other: Uncompensated relationship; Practice Point Communications: Other: Uncompensated relationship; Foundation Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; G1 Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel-Donnelly: Gilead: Research Funding; Boston Biomedical: Research Funding; Roche: Research Funding; LAM Therapeutics: Research Funding. Goldschmidt: Amgen: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Blue Ridge Cancer Care: Current Employment. Boccia: Rigel: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cline: Pfizer: Honoraria; Reflexion Medical: Consultancy, Other: Travel expenses; Texas Oncology: Current Employment. Sacchi: Bristol-Myers Squibb Company: Current Employment. Forero-Torres: Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sims: Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Liu: Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Friedberg: Astellas: Consultancy; Acerta Pharma — A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Bayer: Consultancy; Portola Pharmaceuticals: Consultancy; Roche: Other: Travel expenses; Seattle Genetics: Research Funding; Kite Pharmaceuticals: Research Funding.

*signifies non-member of ASH