Abstract
Patients with relapsed/refractory chronic lymphocytic leukemia (CLL) have excellent responses with kinase or BCL2 inhibitors, but patients with high risk cytogenetics (del(17p) and/or del(11q)) do not seem to achieve long-term disease control. Allogeneic hematopoietic stem cell transplantation (alloHCT) can result in sustained progression-free survival. As non-relapse mortality (NRM) after alloHCT is partly age-dependent, alloHCT is preferably considered in younger high cytogenetic risk CLL patients, but data of early NRM and longer-term PFS lack for this age group. We focused in this study on younger allo-transplanted CLL patients (<50 years) in an EBMT registry cohort with additional data collection (n=197, median follow-up 90.4 months). The most important prognostic factor for 2-year NRM in multivariate analysis was the donor HLA match: HR 2.5, 95% CI: 1.1-5.4 for an HLA-matched unrelated donor, and HR 4.0, 95% CI: 1.4-11.6 for an HLA-mismatched unrelated donor, both versus a matched sibling (Table 1). Predictors for poor 8-year PFS were "no remission at the time of alloHCT" (HR 1.7 (95% CI: 1.1-2.5)) and partially HLA-mismatched unrelated donor (HR 2.8 (95% CI: 1.5-5.2))(Table 2). High risk cytogenetics did not have a significant impact on 8-year PFS. Based on the regression model, a reference patient was created with high risk cytogenetics (del(17p) and/or del(11q)) and "good transplant" characteristics (remission at the time of alloHCT and HLA- and sex-matched sibling donor). The predicted two-year NRM for this patient was 12.1% (95% CI: 2.5%-21.7%)(Figure A) and 8-year PFS 53.5% (95% CI: 38.0%-69.0%)(Figure B). Such a low predicted NRM may keep up with the 9% "real-world" reported 1-year NRM of ibrutinib and the 8-year PFS compares favorably to outcomes after using kinase inhibitors or venetoclax. Taking into account the amount of uncertainty for predicting survival after alloHCT but also for the sequential administration of kinase inhibitors and venetoclax, alloHCT still remains a valid option for younger high cytogenetic risk refractory/relapsed CLL patients with a 10/10 HLA-allele matched donor.
Dreger:Novartis: Speakers Bureau; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Delgado:Janssen: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Schoenland:Jansen: Honoraria, Other: financial support of conference participation, Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schetelig:Sanofi: Honoraria.
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