Stem Cell Transplantation in CLL: Almost Gone but Not Forgotten

Jun 3, 2021 11:00:00 AM / by Champions Oncology

chronic lymphocytic leukemia - blood sample

Advances in molecular diagnostics and ex vivo drug sensitivity screening have greatly improved the use of targeted therapies for the treatment of chronic lymphocytic leukemia (CLL), such as B cell receptor signaling inhibitors, which include the Bruton tyrosine kinase (BTK) inhibitors like ibrutinib[1] and acalabrutinib and the phosphoinositide 3-kinase (PI3K) inhibitors duvelisib and idelalisib[2], as well as the BCL2 inhibitor venetoclax[3]. For most patients that are matched appropriately with these treatments, they show greatly improved progression-free survival and overall survival.

For a subset of patients, these first-line treatments fail due to the development of resistance or severe drug toxicity, and allogeneic hematopoietic stem cell transplantation (allo-HCT) remains one of the only treatment options that can result in durable responses. Allo-HCT involves the transplantation of blood stem cells from donor blood or bone marrow to replace diseased blood cells with healthy donor cells. Allo-HCT requires that recipients undergo high dose chemotherapy or radiation prior to transplantation to destroy malignant cells. In addition to the intensive immunosuppressive conditioning needed prior to transplantation, allo-HCT can cause graft-versus-host disease and organ toxicity, thus making it a potentially high-risk procedure with uncertain outcomes.

03June2021_InsidePicNonetheless, allo-HCT may be the only option remaining for refractory or relapsed patients, and a recent study examined outcomes in patients receiving allo-HCT following one or more failed first line treatments[4]. This retrospective multicenter cohort study followed 65 CLL patients who underwent allo-HCT following one or more prior first-line therapy. Cytogenetic and molecular characteristics were included, as was the type of first-line treatment, which included ibrutinib, venetoclax, PI3K inhibitors, and/or chemotherapy. 24-month progression-free survival (PFS) and overall survival (OS) were 63% and 81% respectively, relapse incidence was 27%, and nonrelapse mortality was 13%. There was also a relatively low incidence of acute or chronic graft-versus-host disease. The overall findings suggest that the number and type of prior treatments does not negatively impact PFS and OS following allo-HCT, and patients with high-risk mutations are also well suited for allo-HCT treatment. Improvements in pre-allo-HCT immunosuppression conditioning treatments have also improved survival outcomes in CLL patients.

Allo-HCT will continue to be a valuable treatment option for some CLL patients, but improvements in specific immunotherapies, including advances in targeted inhibitors and chimeric antigen receptor (CAR) T cells will likely provide more effective first-line treatment options. Improvements in cytogenetic and molecular diagnostics as well ex vivo drug sensitivity screening will also optimize treatment selection for better outcomes in CLL patients.


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[1] Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.

[2] Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.

[3] Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):311-322.

[4] Roeker, Lindsey E., et al. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents. Blood Advances. 2020;4.16: 3977-3989.

Tags: Hematological Malignancies