Background: Despite a 5 to 20-fold higher risk of Hodgkin lymphoma (HL) in people with HIV (PWH) than the general population, PWH were excluded from clinical trials that led to the approval of anti-PD-1 agents (PD-1) in HL. PD-1 have overall response rates (ORR) of 65-70% in the general population and are used in all lines of HL therapy. Several prospective and retrospective studies have shown PD-1 are safe in PWH, but they remain underutilized in HIV-associated HL (HIV-HL) where data are limited.
Methods: Patients (pts) with HIV-HL were identified from the retrospective, international database, “Cancer Therapy using Checkpoint inhibitors in PWH-International (CATCH-IT)” consortium, that is maintained at the Dana-Farber Cancer Institute (DFCI) and approved by DFCI and local institutional review boards. Pts who received either nivolumab or pembrolizumab, alone or in combination with other agents were included. Records were reviewed for demographics, HL and HIV characteristics, and treatment data.
Safety was evaluated by the occurrence of immune-related adverse events (irAEs) per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response to treatment was evaluated using descriptive statistics, and immune reconstitution was measured by changes in CD4 + T cell counts (CD4) from prior to end of PD-1 therapy via paired t-tests. ORR was defined as the proportion of pts with partial or complete response (PR/CR) per the 2014 Lugano classification for HL. Duration of response (DOR) was defined as the time from the date of the first CR or PR to the date of progressive disease (PD) or death. Progression-free survival (PFS) was defined as the time from PD-1 initiation to disease progression, death, or censored on the date of the last follow-up. Overall survival (OS) was defined as the time from PD-1 initiation to death or censored at the last follow-up. DOR, PFS, and OS were evaluated by Kaplan-Meier methodology.
Results: We identified 23 pts with HIV-HL from 12 institutions in the United States: 20 cisgender men, 3 cisgender women; 10 Black,10 White, and 10 Hispanic; median age 48 years [interquartile range (IQR): 36-58]. At HL diagnosis, 19 (83%) pts had advanced stage disease, and in 20 pts where EBV status of the tumor was known, all were positive. Nine (39%) pts had primary refractory disease. The median number of prior systemic therapies was 2 (IQR: 1-3). One pt had PD-1 as 1 st-line therapy, 6 had PD-1 as 2 nd-line therapy, and 16 had PD-1 as ≥3 rd-line therapy. Fourteen (61%) pts received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as 1 st-line therapy. Two pts had prior autologous stem cell transplant (ASCT). At the time of PD-1 initiation, 22 pts (96%) had advanced stage disease, 17 (46%) had extranodal disease, and the median ECOG performance status was 1 (IQR: 0-2). Seventeen (74%) pts received PD-1 monotherapy, 5 (22%) received nivolumab + brentuximab vedotin, and 1 received nivolumab + ifosfamide, carboplatin, and etoposide. Four pts had uncontrolled HIV at the time of PD-1 initiation (HIV viral load range=10,000-2,000,000 copies/mL). All pts received antiretroviral therapy during treatment. Median baseline CD4 was 155 cells/µL (IQR: 66-297) and CD8 was 429 cells/µL (IQR: 158-716). Median CD4 and CD8 increased to 310 and 653 cells/µL at the end of PD-1 treatment (P=0.0084, P=0.32).
The median number of PD-1 cycles was 6 (IQR: 4-21). Three (13%) pts had irAEs (all grade 3): hypothyroidism, autoimmune pancreatitis, and pneumonitis. None required PD-1 discontinuation. The ORR was 83% in the overall cohort. Sixteen pts (70%) had CR, 3 (13%) PR, and 4 (17%) PD as best response. Among the 19 pts with CR or PR, the median DOR was 19.7 months; 8 had PD after initial response and 11 had ongoing CR at data cut-off. Ten pts received consolidation with ASCT after PD-1, 6 of whom had received PD-1 at ≥3 rd line treatment. All pts who received ASCT had ongoing CR at data cut-off. Median PFS was 21.2 months in the overall cohort. Among pts with CD4 <200 and >200 cells/µL, PFS was not statistically different (17.3 vs 29 months; P=0.95). At data cut-off, 17 pts (74%) were alive and 6 (26%) had died due to HIV-HL. Median OS was 23.6 months in the overall cohort.
Conclusion: In HIV-HL, PD-1 blockade was safe, had a high ORR and CR rate, and allowed for immune reconstitution in pts across a wide range of CD4 counts and HIV viral loads. These data add to the evidence that anti-PD-1 agents are effective in PWH and should be used in HIV-HL.
Disclosures
Lurain:EMD-Serrono: Research Funding; Janssen: Research Funding; Lentigen: Research Funding; CTI BioPharma: Research Funding; Eli Lilly: Research Funding; Merck: Research Funding; BMS-Celgene: Research Funding. Ramaswami:EMD-Serrono: Research Funding; Janssen: Research Funding; BMS-Celgene: Research Funding; Merck: Research Funding; Eli Lilly: Research Funding; CTI BioPharma: Research Funding; Lentigen: Research Funding. Abdel-Wahab:ChemoCentryx: Consultancy, Honoraria. Feldman:Seagen: Consultancy, Honoraria, Other: travel expenses, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria; Sankyo: Speakers Bureau; Karyopharm: Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; ADC therapeutics: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Research Funding; Bayer: Honoraria; Kyowa Kirin: Research Funding; Amgen: Research Funding; Viracta Therapeutics: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Secura Bio: Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Daiichi: Speakers Bureau; Juno/Bristol Myers Squibb (BMS): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics LLC/Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola Pharmaceuticals: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Trillium Therapeutics: Research Funding; Pfizer: Research Funding; Genmab: Consultancy, Speakers Bureau; MorphoSys: Speakers Bureau. Kim:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; PierianDx: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Diffusion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Mirati Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Arcus Biosciences: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; BMS: Research Funding; Regeneron: Research Funding; Debiopharm Group: Research Funding; Genentech/Roche: Research Funding. Drakaki:Athos Therapeutics: Current Employment, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Attica Sciences: Current Employment, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Dyania Health: Consultancy, Current Employment, Current holder of stock options in a privately-held company; Urogen Pharma: Current holder of stock options in a privately-held company; Alimera Sciences: Current holder of stock options in a privately-held company; Kyn Therapeutics: Current holder of stock options in a privately-held company; Moderna Therapeutics: Current holder of stock options in a privately-held company; Proteas Bioanalytics: Current holder of stock options in a privately-held company, Patents & Royalties; BMS: Consultancy, Research Funding; AstraZeneca: Consultancy, Other: Travel, accommodations, expenses, Research Funding; Radmetric: Consultancy; Seagen: Consultancy, Other: Travel, accomodations, expenses; Janssen: Consultancy; PACT Pharma: Consultancy; Merck: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Exelixis: Consultancy; Aveo: Consultancy; Kite/Gilead: Research Funding; Jounce Therapeutics: Research Funding; Infinity Pharmaceuticals: Research Funding; Seattle Genetics/Astellas: Research Funding; Immunomedics/Gilead: Research Funding; Harvard Medical School: Patents & Royalties: spouse; UCLA: Patents & Royalties: spouse; Eli Lilly: Other: Travel, accommodations, expenses . Morse:Genentech/Roche: Honoraria, Speakers Bureau; Novartis: Honoraria; Sanofi: Honoraria; Lexicon: Honoraria, Research Funding; Ipsen: Honoraria, Speakers Bureau; Bayer: Honoraria; Taiho Pharmaceutical: Honoraria, Speakers Bureau; Boehringer Ingelheim: Honoraria; Eisai: Honoraria, Research Funding, Speakers Bureau; Merck: Honoraria, Research Funding; Exelixis: Honoraria, Speakers Bureau; AstraZeneca/Daiichi Sankyo: Honoraria, Speakers Bureau; Servier: Honoraria, Speakers Bureau; Tersera: Honoraria; QED Therapeutics: Honoraria; Precision Biologics: Research Funding; BMS: Research Funding; Onyx: Research Funding; Advanced Accelerator Applications: Research Funding; AlphaVax: Research Funding; Duke University: Patents & Royalties. Johnson:Janssen: Membership on an entity's Board of Directors or advisory committees; Iovance: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Catalyst BioPharma: Membership on an entity's Board of Directors or advisory committees; Mallinckrodt: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Mosaic ImmunoEngineering: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Oncosec: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Targovax: Membership on an entity's Board of Directors or advisory committees; Teiko: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding. Mangla:Targeted Oncology: Honoraria; SpringWorks Therpeutics: Consultancy, Research Funding; Nektar: Research Funding; Tracon Pharma: Research Funding; Regeneron: Research Funding. Dittus:GenMab: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; ADC Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Seagen: Research Funding; Astrazeneca: Research Funding. Ravi:Eli Lilly: Research Funding; Telix: Research Funding; Bayer: Research Funding; OncLive: Speakers Bureau. LaCasce:Research to Practice: Consultancy; Seagen, Kite Pharma: Membership on an entity's Board of Directors or advisory committees. 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Herrera:AstraZeneca/MedImmune: Consultancy; Kite, a Gilead Company: Research Funding; Merck: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Regeneron: Consultancy; Tubulis GmbH: Consultancy; BMS: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding; Pfizer: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Karyopharm Therapeutics: Consultancy; Allogene Therapeutics: Consultancy; Seattle Genetics: Consultancy, Research Funding; AbbVie: Consultancy; Genmab: Consultancy; Caribou Biosciences: Consultancy; Gilead Sciences: Research Funding; AstraZeneca: Research Funding.
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