Patients with relapsed/refractory chronic lymphocytic leukemia (CLL) have excellent responses with kinase inhibitors such as ibrutinib or idelalisib + rituximab, or BCL2 inhibitors such as venetoclax, but patients with high-risk cytogenetics (del17p and/or del11q and TP53 mutation) do not seem to achieve long-term disease control and suffer relapse. However, allogeneic hematopoietic stem-cell transplantation (alloHCT) can result in sustained progression-free survival (PFS) independent of cytogenetic risk. As nonrelapse 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 for this age group are lacking. Van Gelder and colleagues reported on a study that focused 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) to identify factors that predict low 2-year NRM and high 8-year PFS. They also studied the impact of del17p and del11q on PFS.
The most important prognostic factor for 2-year NRM in multivariate analysis was the donor HLA match: hazard ratio (HR) of 2.5 (95% confidence interval [CI], 1.1-5.4) for an HLA-matched unrelated donor, and HR of 4.0 (95% CI, 1.4-11.6) for an HLA-mismatched unrelated donor, both versus a matched sibling. 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). High-risk cytogenetics did not have a significant impact on 8-year PFS. Previous autologous HCT was also identified as a risk factor for poor 8-year PFS (HR, 1.9; P=0.03). Based on the regression model, a reference patient was created with high-risk cytogenetics (del17p and/or del11q) and “good transplant” characteristics (remission at the time of alloHCT and HLA- and sex-matched sibling donor). The predicted 2-year NRM for this patient was 12.1% (95% CI, 2.5%-21.7%) and 8-year PFS was 53.5% (95% CI, 38.0%-69.0%). 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. In contrast, a patient with “poor transplant” characteristics (del17p and/or del11q, with no remission at the time of alloHCT, and an unrelated sex-mismatched donor) had a predicted 2-year NRM of 37% and 8-year PFS of approximately 20%. Taking into account the amount of uncertainty for predicting survival after alloHCT and 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. Low-NRM risk factors can be identified in these “good transplant” patients, which will ensure very low NRM and 8-year PFS >50%.
Van Gelder M, et al. ASH 2016. Abstract 522.