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3060 Brentuximab Vedotin in Combination with Nivolumab in CD30+ Malignancies Refractory to Brentuximab Vedotin

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Antibody Therapy, Hodgkin lymphoma, adult, Lymphomas, Clinical Research, Combination therapy, Checkpoint Inhibitor, T Cell lymphoma, Diseases, Therapies, therapy sequence, Lymphoid Malignancies, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Christina Poh, MD1,2, Ryan C Lynch, MD1,2, Edus H Warren, MD, PhD1,2, Chaitra S Ujjani, MD1,2, Stephen D Smith, MD1,2, Michi M Shinohara, MD1,3*, Jonathan R Fromm, MD, PhD4, Xinyi Fan1*, Jenna M Voutsinas, MPH1*, Qian Wu1*, Laura Naylor2*, Heather Rasmussen2* and Ajay K Gopal, MD1,2

1Fred Hutchinson Cancer Center, Seattle, WA
2Division of Hematology and Oncology, University of Washington, Seattle, WA
3Division of Dermatology, University of Washington, Seattle, WA
4Division of Hematopathology, University of Washington, Seattle, WA


Brentuximab vedotin (BV), in combination with multi-agent chemotherapy, is considered a standard of care for newly diagnosed CD30+ lymphomas. Despite high reported efficacy, some patients fail to respond to initial BV exposure and many more eventually progress despite ongoing BV therapy. In addition to direct cytotoxicity, BV may also induce immunogenic cell death (Gardai, et al. Cancer Res 2015) and foster a reduction of regulatory T-cells (Herrera, et al. Blood 2018) that may synergize with immune checkpoint inhibitors. To date, the high response rates reported with BV and anti-PD-1 combinations have been limited to patients naïve to both of these agents (Advani, et al. Blood 2021). To address the more clinically relevant scenario of prior BV +/- anti-PD-1 exposure, we designed a study to evaluate the combination of BV and nivolumab in patients with CD30+ lymphoma refractory to prior BV, including those with prior anti-PD-1 therapy. We report the final safety, efficacy and correlative analysis of BV in combination with nivolumab in R/R CD30+ lymphomas refractory to BV.


We conducted an open-label trial (NCT01703949) involving patients 18 years and older with CD30+ lymphomas refractory to BV therapy. Refractoriness was defined as lack of disease response or progression within 6 months following a minimum of 2 cycles of BV. BV was given at 1.8 mg/kg in combination with nivolumab at 3 mg/kg every 3 weeks for 4 cycles. The primary endpoint was overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival, overall survival, time to next treatment, safety and tolerability and immune response biomarkers.


As of July 27, 2023, 19 patients have enrolled and 17 have initiated therapy (Table 1). Fourteen patients had classical Hodgkin lymphoma (cHL), 2 had ALK-negative anaplastic large cell lymphoma (ALK- ALCL) and 3 had CD30+ mycosis fungoides (MF). Median age was 35 (range 27-71) years and the median number of prior regimens was 5 (range 1-9), including a median of 6 prior cycles of BV (range 2-19). All patients had BV-refractory disease including 16 (84%) who were non-responsive to and 3 (16%) who relapsed within 6 months of BV. Five (26%) patients with cHL received prior anti-PD-1 therapy and 4 (21%) had anti-PD-1 refractory disease. Median time from last BV and anti-PD-1 therapy to study treatment was 5.2 and 1.1 months, respectively. Eight (42%) patients had prior autologous stem cell transplant. Of response evaluable patients, the ORR and CR rate was 44% and 6% after 2 cycles and 44% and 19% after 4 cycles of therapy. Of patients who were refractory to prior BV and anti-PD-1 therapy, 1 (25%) and 1 (25%) achieved a PR and CR, respectively. ORR and CR rate was 43% and 14% for patients with cHL, 100% and 50% for patients with ALK- ALCL, and 100% and 100% for patients with MF, respectively. At completion of study, 1 patient with cHL, 1 with MF and 2 with cHL continued BV with nivolumab, BV monotherapy and nivolumab monotherapy, respectively. Median time to progression and next therapy was 4.5 (range 1.8-45.6) and 5.0 (range 1.8-45.6) months, respectively. Of the 3 patients who achieved a CR after 4 cycles of therapy, 2 (67%) continued treatment (1 with BV and nivolumab and 1 with BV monotherapy), and 1 (33%) has been on surveillance for 45.6 months with no evidence of relapse. At a median follow-up of 21.7 (range 0.5-60.4) months, 15 (79%) patients are alive with 3 in CR. Eleven (58%) and 8 (42%) patients reported no and grade 1 peripheral neuropathy (PN) at baseline, respectively. At end of treatment, 12 (63%) and 1 (5%) patients reported grade 1 and 2 PN, respectively. No patients experienced grade ≥3 PN, transaminitis, infections or infusion reactions. One (5%) patient had a 1-week dose delay due to grade 1 ALT/AST elevation. Two (11%) deaths were noted on study; one patient developed respiratory failure secondary to pneumonitis and influenza and another patient experienced cardiac arrest due to benzodiazepine withdrawal. Correlative PD-1 levels drawn at baseline and at the end of treatment did not correlate with response.


Despite the presence of BV-refractory disease, 4 cycles of BV and nivolumab is tolerable and associated with encouraging efficacy in patients with heavily treated CD30+ lymphoma. This treatment option may have increasing relevance as more patients receive BV or anti-PD-1 therapy as part of initial treatment.

Disclosures: Poh: Acrotech: Consultancy; Incyte: Research Funding; Seattle Genetics: Consultancy; BeiGene: Consultancy. Lynch: Incyte: Research Funding; TG Therapeutics: Research Funding; Bayer: Research Funding; Cyteir: Research Funding; Genentech: Research Funding; Seagen Inc.: Research Funding; Cancer Study Group: Consultancy; Foresight Diagnostics: Consultancy; Rapt: Research Funding; Abbvie: Consultancy; SeaGen: Consultancy; Merck: Research Funding. Ujjani: Astrazeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Other: Travel expenses , Research Funding; PCYC: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Epizyme: Consultancy; Lilly: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Atara: Consultancy. Smith: ADC Therapeutics, AstraZeneca, Ayala (spouse), Bayer, BeiGene, Bristol Myers Squibb (spouse), De Novo Biopharma, Enterome, Genentech, Inc., Ignyta (spouse), Incyte Corporation, Kymera Therapeutics, Merck Sharp and Dohme Corp., MorphoSys, Nanjing Pharmaceu: Research Funding; ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Karyopharm, KITE pharma, Incyte, Numab Therapeutics AG, Abbvie, Coherus Biosciences, advisory board (spouse) Genentech, Inc.: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees. Shinohara: Cabaletta Bio: Research Funding; Kyowa Kirin: Research Funding; Aztex: Research Funding. Fromm: Merck: Research Funding. Gopal: Compliment Corporation: Current holder of stock options in a privately-held company; Incyte, Kite, Morphosys/Incyte, ADCT, Acrotech, Merck, Karyopharm, Servier, Beigene, Cellectar, Janssen, SeaGen, Epizyme, I-Mab bio, Gilead, Genentech, Lilly, Caribou, Fresenius-Kabi: Consultancy; Merck, I-Mab bio, IgM Bio, Takeda, Gilead, Astra-Zeneca, Agios, Janssen, BMS, SeaGen, Teva, Genmab: Research Funding.

OffLabel Disclosure: Brentuximab is approved for use in Hodgkin lymphoma, anaplastic large cell lymphoma and CD30+ CTCL. Nivolumab is approved for use in Hodgkin lymphoma but not in anaplastic large cell lymphoma or CD30+ CTCL

*signifies non-member of ASH