Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, CLL, Clinical Research, Health outcomes research, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Non-Biological therapies, Transplantation (Allogeneic and Autologous)
Methods: This retrospective analysis used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational registry and randomized clinical trials, RESONATE (NCT01578707) and RESONATE-17 (NCT01744691). Adults with relapsed/refractory CLL/SLL with del(17p) received either aHCT (reported to CIBMTR in 2008–2017) or single-agent ibrutinib (420 mg/day; enrollment dates: RESONATE, June 2012–April 2013; RESONATE-17, January 2013–June 2013). Main outcomes measured for patients who received aHCT or ibrutinib were overall survival (OS) and progression-free survival (PFS); additionally for patients with aHCT cumulative incidence of relapse/progression, incidence of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) were reported. Outcome comparisons were estimated by the inverse probability weighting to balance the important confounders: age, sex, race, bulky disease, Rai stage, prior treatment, Eastern Cooperative Oncology Group (ECOG) performance status score, time from diagnosis to treatment, del(11q), del(13q), and trisomy 12.
Results: Among qualified patients with relapsed/refractory CLL/SLL and del(17p), the median follow-up was capped at 60 months for the aHCT cohort (n=145); median follow-up for ibrutinib (n=196) was 64 and 33 months for RESONATE (n=53) and RESONATE-17 (n=143), respectively. Median age among patients in the aHCT versus ibrutinib cohort was 58.9 versus 64.5 years (P<0.001), and 70% versus 34% (P<0.001) had an ECOG performance status score of 0; the median time from diagnosis to treatment was 42 versus 70 months (P<0.001), and the proportion of patients with a bulky disease was 18% versus 52% (P<0.001). Of patients with aHCT, 77% underwent reduced-intensity or nonmyeloablative conditioning, 83% received calcineurin inhibitors with mycophenolate or methotrexate as GVHD prophylaxis, and 29% received antithymocyte globulin. At 60 months after aHCT, the cumulative incidence (95% CI) of disease relapse and NRM were both 37% (0.29–0.45); the cumulative incidence (95% CI) was 53% (0.45–0.61) for grade 2–4 acute GVHD and 67% (0.59–0.74) for chronic GVHD. After adjusting for confounders patients treated with ibrutinib had significantly longer OS (adjusted HR=0.39, 95% CI: 0.23–0.68, P=0.0008) and PFS (adjusted HR=0.43, 95% CI: 0.27–0.69, P=0.0005) versus those with aHCT.
Conclusion: This retrospective analysis suggests that ibrutinib treatment may offer improved OS and PFS outcomes over aHCT in patients with relapsed/refractory CLL/SLL and del(17p).
Disclosures: Awan: Dava Oncology: Consultancy; Loxo Oncology: Consultancy; AbbVie/Pharmacyclics: Consultancy, Research Funding; BMS: Consultancy; Genmab: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; BeiGene: Consultancy; Adaptive Biotechnologies: Consultancy; Incyte: Consultancy. Liu: AbbVie: Current Employment, Current holder of stock options in a privately-held company. Huang: Everest Clinical Research: Consultancy, Current Employment, Research Funding; AbbVie: Consultancy, Current Employment, Research Funding. Krigsfeld: Inovio: Current holder of stock options in a privately-held company; Dynavax: Current holder of stock options in a privately-held company; Moderna: Current holder of stock options in a privately-held company; Pharmacyclics LLC, an AbbVie Company: Current Employment, Other: travel, accommodations, expenses; BMS: Current Employment, Current holder of stock options in a privately-held company, Other: travel, accommodations, expenses; AbbVie: Current Employment, Current holder of stock options in a privately-held company, Other: travel, accommodations, expenses. Raz: AbbVie: Current Employment, Current holder of stock options in a privately-held company. Wolfe: Curio Sciences: Other: Paid Lecture. Hamadani: Sanofi Genzyme: Speakers Bureau; AstraZeneca: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; DMC, Inc: Speakers Bureau; CRISPR: Speakers Bureau; Byondis: Consultancy; BeiGene: Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; Omeros: Consultancy; CRISPR: Consultancy; Forte Biosciences: Consultancy; Takeda: Research Funding; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy; BMS: Consultancy; Autolus: Consultancy; Caribou: Consultancy; Astellas Pharma: Research Funding; Allovir: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; Genmab: Consultancy.
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