Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents

Abstract

Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation–specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.

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

“…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.…”

Targeting Bruton’s Tyrosine Kinase in CLL

“…In the modern era, allogeneic hematopoietic stem cell transplant has become safer and more accessible. Recent retrospective analyses of transplant outcomes in CLL reported 2-year PFS of 63% ( 125 ) and 3-year non-relapse mortality of 7% in patients who were previously treated with targeted agents ( 126 ). Treatment with CD19 CAR T can also achieve high rates of initial response in patients who failed ibrutinib ( 115 ).…”

The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

“…In this study, the investigators observed that PFS was predicted by the hematopoietic cell transplantation-specific comorbidity index. No differences were observed among the patients receiving previous TA (one or two ibrutinib/venetoclax) or TA and CIT as the previous treatment [ 235 ]. Currently, most guidelines recommend it for patients with high-risk CLL that have relapsed or are refractory to at least one TA or in cases of clonally related Richter transformation with a response to chemotherapy [ 202 , 236 ].…”