Outcomes of Autologous Stem Cell Transplant in Older Adults with Relapsed/Refractory Classic Hodgkin Lymphoma

Introduction: Adults older than 60 years constitute 20-25% of newly diagnosed classic Hodgkin lymphoma (cHL) and have inferior outcomes compared to younger patients (pts). Salvage therapy followed by an autologous stem cell transplant (ASCT) is a potentially curative option for pts with relapsed/refractory (R/R cHL). There is limited data regarding outcomes of older adults with R/R cHL who undergo ASCT in the current era where novel agents are employed in the R/R setting, in comparison with younger patients.

Methods: This multicenter, international, retrospective study of 18 participating institutions included adults with R/R cHL who underwent ASCT from January 1, 2010 through December 31 2020. Retrospective chart review was performed to collect data on patient and disease characteristics at relapse, including lines and type of salvage therapy, pre-ASCT response by PET, and use of brentuximab vedotin (BV) as consolidation post-ASCT. Study objectives were to assess progression-free survival (PFS), overall survival (OS), and the probability of non-relapse mortality (NRM) with relapse as a competing event. NRM was defined as death without preceding relapse.

Results: Of the total 1172 adults with R/R cHL enrolled in the parent cohort, 96 (8.1%) were age 60 years or older at the time of ASCT. In this older cohort, the median age was 66 years (range: 60-72). 54 (56%) were age 60-64, 31 (32%) were of age 65-69 and 11 (11%) were of age 70-72. 59 (61%) were male, 63 (66%) had advanced stage disease, 17 (18%) had bulky disease, 37 (39%) had B symptoms and 38 (40%) had extranodal disease. All patients (pts) received ABVD or ABVD-like frontline therapy. The median time to relapse was 6 months (range: 0-174). 48 pts (50%) relapsed within a year after completion of frontline treatment and 25 (26%) had primary refractory disease. Salvage therapy prior to ASCT included platinum-based chemotherapy (65%), BV-based regimen (34%), and PD-1 inhibitor-based regimens (3%). 16 pts (16%) underwent ASCT after >1 line of salvage therapy and 75 (78%) underwent ASCT after achieving a complete metabolic response (CMR). 14 pts (14.6%) received BV consolidation.

Median follow-up for entire population was 53.4 months (range: 0.3-199.0). In older adults, the 5-year PFS was 54.2% (CI₉₅: 43.4-67.6) not statistically different compared to pts <60 years (67.7% (CI₉₅: 64.3-71.3), p=0.2). However, 5-year OS was inferior in older adults: 71.9% (CI₉₅: 43.4-67.6) vs. 82.6% (CI₉₅: 43.4-67.6) in pts <60 years (p <0.0001)). In pts ≥60, 26 (27%) died including 12 (12.5%) without preceding relapse. Older adults had 3-month, 1-year and 5-year probability of NRM of 5.2% (CI₉₅: 2.2-12.2), 7.5% (CI₉₅: 3.6-15.3), and 10.9% (CI₉₅: 5.8-20.8), respectively. NRM was significantly higher in older adults compared to pts <60 who had 3-month, 1-year and 5-year probability of NRM of 0.3% (CI₉₅: 0.1-1.0), 0.9% (CI₉₅: 0.5-1.7), and 2.5% (CI₉₅: 1.6-3.9), respectively (p<0.0001). Older adults had 3-month, 1-year and 5-year probability of relapse of 1% (CI₉₅: 0.2-7.3), 7.5% (CI₉₅: 3.6-15.3), and 28.6% (CI₉₅: 19.1-42.1), respectively, which did not differ significantly from younger pts (p=0.3) who had 3-month, 1-year and 5-year probability of relapse of 0.6% (CI₉₅: 0.3-1.3), 5.1% (CI₉₅: 3.8-6.6), and 29.9% (CI₉₅: 26.6-33.5), respectively.

Conclusions: Although older adults with cHL are more likely to relapse after frontline treatment, only a minority of pts (<10%) in this large multicenter cohort underwent ASCT at age ≥60. In select older adults who underwent ASCT, the risk of relapse was similar to younger pts, but NRM was significantly higher, especially in the early post-ASCT period. Detailed assessment of comorbidity scores, toxicities of salvage therapies, and prognostic factors will be presented at the conference.

Desai:Onclive: Honoraria; CurioScience: Honoraria; Merck: Research Funding; Beigene: Research Funding. Spinner:Gilead/Kite: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Bachanova:Citius: Research Funding; Incyte: Research Funding. Evens:Incyte: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Kahl:Genentech: Consultancy; Roche: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Lilly: Consultancy; Novartis: Consultancy; Kite: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; Merck: Consultancy; ADCT: Consultancy. Dorritie:BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Kite-Gilead: Research Funding; Hoffman La-Roche: Research Funding; Genmab: Research Funding. Kenkre:Ipsen: Research Funding. Ansell:Affimed: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; AstraZeneca: Research Funding; Bristol Myers Squibb: Research Funding; Pfizer: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding; SeaGen: Research Funding; Takeda: Research Funding. Shah:Incyte, Epizyme, Seattle Genetics, Loxo Oncology, Acerta: Research Funding; AbbVie, Seattle Genetics: Consultancy. Wagner-Johnston:Beigene: Consultancy; Merck: Research Funding; Genentech: Research Funding; Astra Zeneca: Research Funding. Nowakowski:AbbVie Inc.: Consultancy; MorphoSys AG: Consultancy, Research Funding; TG Therapeutics Inc: Consultancy; ADC Therapeutics: Consultancy; Bantam Pharmaceutical, LLC: Consultancy; Segen: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; F. Hoffmann-La Roche Limited: Consultancy; Constellation Pharmaceuticals: Consultancy; Kymera Therapeutics: Consultancy; Karyopharm Therapeutics: Consultancy; MEI Pharma: Consultancy; Fate Therapeutics: Consultancy; Genentech: Consultancy; Blueprint Medicines Corporation: Consultancy; Celgene Corporation: Consultancy, Research Funding; Debiopharm: Consultancy; Daiichi Sankyo: Consultancy; Zai Laboratory: Consultancy; Ryvu Therapeutics: Consultancy; Selvita Inc: Consultancy; Curis: Consultancy, Research Funding; Incyte Corporation: Consultancy. Mocikova:Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jagadeesh:Affimed, Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; AstraZeneca, ATARA Biotherapeutics, Debio Pharma, LOXO Pharmaceuticals, MEI Pharma, Regeneron Pharmaceuticals, Inc., Seagen, Trillium Pharmaceuticals: Research Funding. Blum:BMS: Research Funding; Seattle Genetics: Research Funding. Diefenbach:FATE Therapeutics: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Millenium: Research Funding; Merck: Consultancy, Research Funding; Gilead: Current equity holder in publicly-traded company, Research Funding; Genmab: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; I MAB: Consultancy, Current equity holder in private company; NYU Grossman School of Medicine/Perlmutter Cancer Center at NYU Langone Health: Current Employment; OverT Therapeutics: Current equity holder in private company; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding. Prochazka:Abbvie: Consultancy; Eli Lilly: Consultancy; Novartis: Consultancy; Swixx: Consultancy, Speakers Bureau. Advani:Seattle Genetics: Research Funding; Cyteir: Research Funding; Regeneron: Research Funding; Autolus: Honoraria, Other: DSMB/Advisory Boards; Gilead: Research Funding; Merck: Other: Steering committee, DSMB/Advisory Boards, Research Funding; ADCT: Honoraria, Other: DSMB/Advisory Boards; BeiGene: Honoraria, Other: DSMB/Advisory Boards, Research Funding; Roche/Genentech: Honoraria, Other: Steering committee, DSMB/Advisory Boards, Research Funding.