Allogeneic hematopoietic cell transplantation after prior targeted therapy for high-risk chronic lymphocytic leukemia

Abstract

Allogeneic hematopoietic cell transplantation (alloHCT) can cure previously treated high-risk chronic lymphocytic leukemia (CLL) patients if they are suitable for transplant through the graft-versus-leukemia effect. However, since the emergence of targeted therapies, the role of alloHCT for high-risk CLL is less clear. To address this question, we evaluated 108 high-risk CLL patients who underwent alloHCT from 2010 to 2018. Thirty patients from the period of 2013 to 2018 received targeted therapy prior to alloHCT. The median age for the targeted therapy cohort was 60 years (range, 30-71 years), and 20% and 73% had complete and partial remission, respectively: 76% had del(17p), 46.2% had 5 or more cytogenetic abnormalities, and 78.9% were IGHV unmutated. The median number of prior therapies was 4 (range, 1-9). With a median follow-up time of 36 months (range, 10-72 months), the 3-year overall (OS) and progression-free survival (PFS) were 87% and 69%, respectively. The 3-year cumulative incidence of nonrelapse mortality and relapse was 7% and 24%, respectively. For the control cohort of 78 patients who underwent alloHCT from 2010 to 2014 and received only chemoimmunotherapy prior to transplant, the 3-year OS and PFS were 69% and 58%, respectively. Patients treated with targeted therapy prior to alloHCT had a significantly higher number of circulating T and B cells and a lower ratio of CD4 regulatory T cells to CD4 conventional T cells early after transplant. In summary, despite multiple high-risk features, the clinical outcome of CLL patients who receive targeted therapy prior to transplant is excellent and alloHCT should be offered while the disease is under control.

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter’s transformation

“…A recent singlecenter retrospective analysis of 108 patients with high-risk CLL, among whom 30 had received a novel agent before receiving HSCT, suggested favorable outcomes for patients who received previous novel therapy with 3-year PFS and OS of 72% and 87%, respectively, vs 58% and 69%, respectively, for patients who received only chemoimmunotherapy, but these differences were not statistically significant (P 5 .3 and P 5 .22, respectively). 9 Taken together, these findings and ours suggest that exposure to novel agents before HSCT does not have a negative impact on outcomes and perhaps might be advantageous. Data from larger registries are needed to more definitely answer this question.…”

“…6 However, few studies have investigated the possible impact of previous exposure to these novel agents on HSCT outcomes. [7][8][9] With this study, we aimed to help further determine the impact of exposure to novel agents on post-HSCT outcomes in patients with CLL and those with CLL-RT.…”

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

“…OS and PFS appeared similar regardless of whether patients had received one versus two or more novel agents or a BTK versus a BCL2 inhibitor as the most recent line of therapy before allogeneic HCT. Encouragingly, both studies also reported low risks of TRM at 7% and 13% with modern transplantation techniques (100,120). It is conceivable that modern CLL therapies have the potential to improve the outcomes of allogeneic HCT by optimizing pretransplant disease control or by inducing less toxicity compared to conventional chemotherapy.…”

Cellular Therapy in High-Risk Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter Syndrome

“…The cumulative incidence of relapse and non-relapse mortality (NRM) was 24% and 7%, respectively. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was the only baseline clinical features (including HLA matching status, number and type of prior targeted inhibitors, and adverse genetic features) associated with an increased risk of death [hazard ratio (HR), 1.4; p=0.032] on univariable analysis ( 56 ).…”