Updates in Front-Line Treatment of Chronic Lymphocytic Leukemia

CLL is the most common leukemia in adult patients in the western world, with 21,040 estimated new cases in 2020.

Prognostic criteria, age, and comorbidities drive the selection for front-line treatment for chronic lymphocytic leukemia (CLL). Meanwhile, therapies such as BTK inhibitors and BCL2 inhibitors have become the new mainstay for treating CLL, according to a presentation at the Hematology/Oncology Pharmacy Association virtual 2021 conference.

Charlene Kabel, PharmD, BCOP, clinical pharmacy specialist, Adult Leukemia Service Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, discussed CLL patient characteristics that influence selection of front-line therapy, including genomics, comorbidities, and performance status, as well as how to select a proper treatment regimen based on a patient profile.

CLL is the most common leukemia in adult patients in the western world, with 21,040 estimated new cases in 2020. CLL predominantly affects Caucasian, elderly males between 67 and 72 years of age, with a majority of patients having more than or equal to 1 comorbidity at diagnosis, according to Kabel.

Current front-line treatments for these age groups, frail or fit, include acalabrutinib ± G, ibrutinib, and venetoclax ± G, although there are many alternatives, such as ibrutinib + R, ibrutinib + G, and HDMP + R. However, there are treatment challenges in more than 70% of patients older than 65 years of age, as up to 90% of patients have a comorbidity at diagnosis.

“Patients’ comorbidities can drive treatment selection, such as atrial fibrillation, gastric ulcer, migraines, and chronic kidney disease,” Kabel said. “Treatment can be patient-dependent, considering compliance, convenience, financial toxicity, and duration of therapy.”

Kabel added that additional front-line trials comparing Bruton’s tyrosine kinase (BTK) inhibitors and BCL2 inhibitors, with or without CD20 monoclonal antibodies, are warranted. Ibrutinib and acalabrutinib are approved BTK inhibitors for CLL and are known for inhibiting CLL cell survival and proliferation. Meanwhile, venetoclax (Venclexta) is the only FDA-approved BCL-2 inhibitor for CLL, and inhibition of BCL-2 allows for natural apoptosis of CLL cells.

Time definitive and chemoimmunotherapy-free approaches are the future direction of upfront treatment in CLL, according to Kabel.

“Some unanswered questions, however, include doublet versus triplet combinations with novel targeted agents, early discontinuation of BTK inhibitors, and MRD testing and its impact on clinical outcomes.”

Editor's Note: This article was updated on April 23, 2021 to accurately represent the content of the presentation.


Kabel C. Updates in Front-Line Treatment of Chronic Lymphocytic Leukemia. Presented at: Hematology/Oncology Pharmacy Association 2021 virtual conference; April 15, 2021. Accessed April 15, 2021.