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233 Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin LymphomaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Hodgkin Lymphoma Clinical Trials
Hematology Disease Topics & Pathways:
Clinical Trials, Clinical Research, Clinically Relevant
Saturday, December 11, 2021: 3:00 PM

Ryan C. Lynch, MD1, Chaitra S. Ujjani, MD1, Christina Poh, MD2, Edus H. Warren, MD, PhD3, Stephen D. Smith, MD4, Mazyar Shadman, MD1, Andrei R Shustov, MD5, Brian G. Till, MD3, Yolanda D. Tseng, MD6*, Hilary Coye, PA-C7*, Megan Shelby, PA-C7*, Susan Ottemiller, ARNP, DNP7*, Hongyan Du, MD5*, Jacquelin Vandermeer, BS8*, Heather A. Rasmussen, BS5*, Stefan Alig, MD9*, Ash A. Alizadeh, MD, PhD9, Avanti Gulhane, MD10*, Delphine Chen, MD10*, Eric Wayne Dean, MD7*, Jason Lukas, MD, PhD7*, Paul S. Martin, MD7, Edmond A Marzbani, MD5*, Jenna Voutsinas, MPH11* and Ajay K Gopal, MD12

1University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA
2Division of Medical Oncology, University of Washington, Seattle, WA
3Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
4Division of Medical Oncology, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA
5University of Washington, Seattle, WA
6Department of Radiation Oncology, University of Washington, Seattle
7Seattle Cancer Care Alliance, Seattle, WA
8University of Washington, Seattle
9Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA
10Department of Radiology, University of Washington, Seattle, WA
11Fred Hutchinson Cancer Research Center, Seattle
12University of Washington/Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA

Introduction

ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) represents standard frontline therapy for classical Hodgkin lymphoma (CHL) in North America. Substituting brentuximab vedotin for bleomycin in this regimen demonstrated improved efficacy in advanced stage patients (pts) but also increased toxicity (Connors et al NEJM 2017). PD-1 inhibitors are highly active in relapsed/refractory CHL, and the first-line setting may represent the ideal time for incorporating PD1 inhibition given the relatively intact host immunity and juxtaposition of malignant cells with T cells in the tumor microenvironment.

Methods

This was a single arm pilot study combining pembrolizumab with AVD in untreated CHL of any stage. Eligibility requiredECOG 0-1, adequate organ function, and measurable disease. The trial intended to enroll 30 pts. AVD was given at standard doses on days 1 and 15 of a 28-day cycle. Pembrolizumab (200 mg IV) was given starting cycle 1 day 1 and every 21 days thereafter (cycle 1 day 22, cycle 2 day 15 etc.). The primary objective was to estimate the safety of delivering 2 cycles of APVD. The secondary objective was to estimate the FDG-PET2 negative (Deauville score 1-3) rate after 2 cycles of APVD. Exploratory objectives included overall and progression free survival, predictive capacity of PET2 after APVD, analysis of ctDNA as well as assessments of metabolic tumor volume. After PET2 response assessment, subjects could continue APVD for up to 6 total cycles as deemed appropriate for their stage/risk factors (including alternate systemic therapy or radiotherapy).

Results

All 30 subjects have enrolled and received at least 2 cycles of therapy. Median age was 32 years (range 18-69). Most pts had advanced stage (stage I n =1 (3%), stage II n=11 (37%), stage III n=7 (23%), stage IV n=11, (37%)). Thirteen (43%) pts had B symptoms at diagnosis and 5 (17%) had bulky disease. Among the 30 pts enrolled, 28 are evaluable for response (one pt declined interim-PET and further treatment and final patient will have PET2 shortly after abstract deadline.Nineteen (68%) pts were PET2 neg (5PS 1-3). No PET2+ pts have progressed to date. End of therapy (EOT) PET negativity (after 2-6 cycles) was 78% (18/23). Among the 5 pts with residual FDG uptake at EOT, only 1 (20%) has developed recurrent lymphoma.

With median follow-up of 10.3 months, 1-year PFS and OS were 96% and 100%, respectively. Six (20%) pts required interruption of pembrolizumab due to toxicity, primarily grade ≥ 2 transaminitis (83%). Those with grade 2 transaminitis (2/6) completed chemotherapy prior to resolving to grade 1 and did not receive additional pembrolizumab. Those with grade ≥ 3 transaminitis (3/6) were required to permanently discontinue pembrolizumab. All transaminitis was transient and resolved with steroids and/or withholding pembrolizumab. No pneumonitis and no other grade ≥ 3 immune-related AEs were observed. Toxicities were otherwise similar to those expected with ABVD chemotherapy. No pt had a treatment delay of > 21 days during the first 2 cycles, and no pt who interrupted pembrolizumab due to toxicity has relapsed. Updated efficacy and more detailed safety data will be presented at the meeting.

Conclusion

Pembrolizumab + AVD without a PD-1 lead-in is safe and effective therapy for frontline HL. In this study, PET2+ following APVD does not appear to be associated with high risk of disease relapse. Additional analyses of MTV and ctDNA are ongoing to better understand these results. Concurrent APVD, without an anti-PD-1 run-in, represents a well-tolerated, and efficacious backbone that can be further evaluated in all stages of CHL.

Disclosures: Lynch: Cyteir: Research Funding; SeaGen: Research Funding; RAPT: Research Funding; Bayer: Research Funding; Incyte: Research Funding; Genentech: Research Funding; Morphosys: Consultancy; TG Therapeutics: Research Funding; Juno Therapetics: Research Funding. Ujjani: Atara, AstraZeneca, AbbVIe, ACDT, Epizyme, TG Therapeutics, Pharmacyclics, Beigene: Consultancy. Poh: Morphosys: Consultancy; Acrotech: Honoraria; Incyte: Research Funding. Smith: Karyopharm: Consultancy; Beigene: Consultancy, Research Funding; KITE pharm: Consultancy; Bristol Myers Squibb (spouse): Research Funding; Acerta Pharma BV: Research Funding; De Novo Biopharma: Research Funding; Genentech: Research Funding; Millenium/Takeda: Consultancy; Ignyta (spouse): Research Funding; AstraZeneca: Consultancy, Research Funding; Bayer: Research Funding; Incyte Corporation: Research Funding; ADC Therapeutics: Consultancy; Incyte: Consultancy; Portola Pharmaceuticals: Research Funding; Ayala (spouse): Research Funding; Merck Sharp & Dohme Corp: Research Funding. Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding. Shustov: Seagen Inc.: Research Funding. Till: Mustang Bio: Consultancy, Patents & Royalties, Research Funding. Alizadeh: Gilead: Consultancy; Janssen Oncology: Honoraria; Roche: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Foresight Diagnostics: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Bristol Myers Squibb: Research Funding; Forty Seven: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; CAPP Medical: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cibermed: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Gopal: Teva: Research Funding; Servier: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; SeaGen: Consultancy, Honoraria, Research Funding; Incyte: Honoraria; IGM Biosciences: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Research Funding; I-Mab bio: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Cellectar: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Acrotech: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Kite: Consultancy, Honoraria; MorphoSys: Honoraria; Nurix Inc: Consultancy, Honoraria; Bristol Meyers Squibb: Research Funding.

*signifies non-member of ASH