Allogeneic Hematopoietic Stem Cell Transplant Effective for Patients with CLL Previously Treated with Novel Agents

September 3, 2020

Allogeneic hematopoietic stem cell transplant’s role in the chronic lymphocytic leukemia has changed due to new novel agents, but research shows its still effective despite novel agent exposure.

Novel agents are becoming an important part of the chronic lymphocytic leukemia landscape as they improve outcomes for patients, but the number of novel agents used prior to allogeneic hematopoietic stem cell transplant (alloHCT) and after do not have an impact on survival outcomes.

AlloHCT was the standard of care for patients with early relapse or refractory chronic lymphocytic leukemia (CLL) and provided an opportunity for long-term disease control in the absence of other treatments. Now, novel agents such as Imbruvica (ibrutinib), Calquence (acalabrutinib) and Venclexta (venetoclax) are improving response rates, progression-free survival (PFS) and overall survival (OS) in patients and paving the way for long-term disease control depending on sequential treatment. Moreover, these novel agents don’t come with the same risks as alloHCT such as graft-versus-host-disease (GVHD), organ toxicity and non-relapse mortality (NRM).

However, some patients still face initial barriers with these novel agents and all of the novel agents may not work for them, but researchers have determined that alloHCT remains an option for these patients and is not adversely impacted by novel agents. In a study of 65 patients with CLL who underwent one or more treatments with novel agents, whether prior to alloHCT or after, researchers found a two-year PFS of 63%, OS of 81%, NRM of 13% and relapse incidence of 27%. Moderate to severe GVHD developed in 27% of patients.

“The data presented here support consideration of alloHCT for novel agents treated, fit patients, with responding disease,” the authors wrote, “and should be considered particularly for patients in whom novel agents are not expected to provide long-term disease control.”

Ninety-two percent of patients received novel agent immediately prior to alloHCT treatment with a 6% complete response for those receiving Imbruvica, 97% of patients then discontinued it before alloHCT treatment. Patients receiving Venclexta-based therapy prior to alloHCT had a 52% complete response and 95% discontinued treatment prior to alloHCT with intolerance of the therapy in 5%.

After alloHCT treatment, researchers looked at patients in two arms, those who were exposed to one novel agent versus two or more novel agents with similar poor risk features and a similar median age of 60. Both groups had similar PFS and OS outcomes that were not significantly different and that exposure to these novel agents prior to alloHCT were also predictors of PFS after alloHCT treatment with no significant differences between the arms. The predicated outcomes were initially estimated at 66% PFS and 94% OS. Those results suggest that alloHCT is still a meaningful treatment even when patients with CLL are exposed to novel agents, the authors explained.

“Taken together, this study suggests that alloHCT is safe and effective in patients with CLL exposed to one or more novel agents prior to alloHCT,” they concluded. “These data support the use of alloHCT for well-selected patients with high-risk CLL.”


x