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472 Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

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, Therapies, Hodgkin Lymphoma, checkpoint inhibitors, immunotherapy, Lymphoid Malignancies, Clinically relevant, transplantation
Sunday, December 6, 2020: 2:30 PM

Alex F. Herrera, MD1, Lu Chen, PhD2*, Yago Nieto, MD3, Leona Holmberg, MD, PhD4*, Patrick B. Johnston, MD/ PhD5, Matthew Mei, MD6, Leslie Popplewell, MD1*, Saro H. Armenian, DO, MPH7, Thai Cao, MD8*, Len Farol, MD9*, Firoozeh Sahebi, MD10, Ricardo Spielberger, MD9*, Robert Chen, MD11, Auayporn P. Nademanee, MD, BS12, Lacolle Peters1*, Neena Kennedy1*, Steven T. Rosen, MD13, Larry W. Kwak, MD, PhD14, Stephen J. Forman, MD15 and Tatyana A. Feldman, MD16

1City of Hope, Duarte, CA
2Department of Information Sciences, City of Hope, Duarte
3Department of Stem Cell Transplantation and Cellular Therapy, UT M.D. Anderson Cancer Ctr., Houston, TX
4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
5Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
6Gehr Family Center for Leukemia Research, City of Hope Medical Center, Duarte, CA
7Department of Population Sciences, City of Hope, Duarte, CA
8Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
9Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA
10Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA
11Autolus Limited, London, United Kingdom
12Department of Hematology/HCT, City of Hope Nat'l. Med. Ctr., Duarte, CA
13Beckman Research Institute, City of Hope, Duarte, CA
14Deputy Director, City of Hope Comprehensive Cancer Center, Duarte, CA
15Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
16Hackensack University Medical Center, NY, NY

Introduction: Standard of care for patients (pts) with relapsed or refractory (RR) Hodgkin lymphoma (HL) is salvage therapy (tx) followed by autologous hematopoietic cell transplantation (HCT). However, most pts with high-risk RR HL will relapse after HCT. The AETHERA study demonstrated that post-HCT consolidation with brentuximab vedotin (BV) in high-risk HL pts improved progression-free survival (PFS) compared to placebo, particularly in pts with 2+ risk factors (Moskowitz, 2018). Pts with prior BV exposure were excluded from AETHERA, and BV is increasingly used prior to HCT in HL. PD1 blockade is effective in pts with RR HL and PD1 monotherapy as post-HCT consolidation in HL resulted in promising 18 mo PFS (Armand, 2019). Combined BV and nivolumab (Nivo) is a safe and effective salvage tx in HL, therefore we conducted a multicenter phase 2 study to evaluate the safety and efficacy of BV-Nivo post-HCT consolidation in high risk RR HL.

Methods: After HCT, adult pts with high-risk HL defined as having ≥ 1 of the following modified AETHERA risk factors were eligible: primary refractory HL, relapse < 1 year of completing initial tx, extranodal disease (dz) at relapse, B symptoms (sx) at relapse, requiring > 1 salvage tx, not in CR at HCT. Prior BV or PD1 blockade were allowed if pts were not refractory. Pts underwent HCT according to institutional standards at the 5 centers. Starting between day 30-75 after HCT, pts received 1.8 mg/kg of BV and 3mg/kg nivo q21 days for a planned 8 cycles. If 1 drug was discontinued due to toxicity, the other could be continued. Investigators assessed response and progressive disease (PD) according to the 2014 Lugano classification. The primary endpoint was 18 mo PFS from study tx initiation. Secondary endpoints were overall survival (OS), safety, and the response rate in pts not in complete response (CR) at baseline.

Results: 59 pts were enrolled and treated with at least one dose of study tx. Baseline characteristics are listed in Table 1. 18 (31%) pts were primary refractory, 35 (59%) had early relapse, 23 (39%) had extranodal dz and 14 (24%) had B sx at relapse, 15 (25%) received > 1 salvage tx before HCT, and 48 (81%) were in CR at HCT. 21 (36%) had 1 modified AETHERA risk factor, 23 (40%) had 2 and 14 (24%) had 3+ risk factors. The median follow-up time from study tx initiation was 15.7 months (range, 2.8-35.5).

Patients initiated BV-nivo a median 54 days from HCT (range, 34-75) and received a median of 8 cycles (range, 1-8). 29 (49%) pts completed all 8 cycles of BV and nivo and 45 (76%) patients completed 8 cycles of one drug. 14 (24%) pts discontinued both BV and nivo early, including 6 for adverse events (AE), 6 pt withdrawals, 1 pt lost to follow-up, and 1 pt death from PJP pneumonia unrelated to study tx. BV was discontinued in 8 (14%) pts – due to grade (gr) 3 peripheral neuropathy (PN) in 2 pts, gr 2 PN in 2 pts, carpal tunnel syndrome in 1 pt, gastrointestinal AEs in 2 pts, and infusion related reaction in 1 pt. Nivo was discontinued in 7 (12%) pts – due to pneumonitis in 2 pts, and colitis, elevated bilirubin, abnormal transaminases, pneumonia with elevated creatinine, and hypotension with fever in 1 pt each. BV was dose reduced to 1.2mg/kg in 11 (19%) pts, 9 pts for PN, and 1 each for neutropenia and arthralgia. The most common AEs related to BV-Nivo consolidation were PN (51%, 3% gr 3), neutropenia (42%, 31% gr 3-4), fatigue (37%), diarrhea (29%, 3% gr 3), nausea (25%, 2% gr 3), arthralgia (24%), AST elevation (24%, 2% gr 3). The most frequent gr 3-4 AEs were neutropenia (31%), pneumonitis (7%), and ALT elevation (5%). Immune-related (ir) AEs requiring systemic corticosteroids occurred in 18 (31%) patients. Most common Gr 2 or higher irAEs included: pneumonitis (12%), AST or ALT elevation (8%), hypothyroidism (5%), and rash (3%).

6 pts were not in CR at baseline after HCT (all PR). 5 pts converted to CR with study tx and 1 pt remained in PR without PD. There were only 2 PFS events, 1 pt with relapse at 15 months and PJP-related death after prophylaxis was self-discontinued. The estimated 18 mo PFS and OS in all patients were 95% and 98%, respectively. The estimated 18 mo PFS in pts with 2+ and 3+ risk factors were 92% and 89%, respectively.

Conclusions: Post-HCT consolidation with BV-Nivo in pts with high-risk RR HL is a promising approach, with only 1 relapse observed in our cohort with short follow-up thus far. Post-HCT BV-Nivo was tolerable, though IrAEs were observed more frequently than in the pre-HCT setting and PN and neutropenia were common.

Disclosures: Herrera: Pharmacyclics: Research Funding; Karyopharm: Consultancy; AstraZeneca: Research Funding; Gilead Sciences: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Nieto: Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support. Holmberg: Sanofi: Research Funding; Seattle Genetics: Research Funding; Millenium-Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; UpToDate: Patents & Royalties: Royalties; Janssen: Research Funding; Merck: Research Funding. Mei: Sanofi: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees. Chen: Autolus Therapeutics: Current Employment. Rosen: Abbvie: Speakers Bureau; Seattle Genetics: Consultancy; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau. Kwak: Theratest: Current equity holder in private company; Pepromene Bio: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy; InnoLifes, Inc: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Sellas Life Sciences Grp: Consultancy; CJ Healthcare: Consultancy; Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees. Feldman: Portola: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Trillium: Research Funding; Janssen: Speakers Bureau; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; AstraZeneca: Consultancy.

OffLabel Disclosure: Nivolumab is not FDA-approved for use as consolidation after autologous stem cell transplantation

*signifies non-member of ASH