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Acalabrutinib Treatment in Very Old and Frail Patients with Chronic Lymphocytic Leukemia (CLL) – ICML 2023

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Authored by Dr. Brian Koffman

The Bottom Line:

No new concerns or safety signals were found in old and frail chronic lymphocytic leukemia (CLL) patients treated with acalabrutinib.

Who Performed the Research and Where Was it Presented:

Dr. Simon of the German CLL Study group led the presenters at ICML (International Conference on Malignant Lymphomas) 2023 in Lugano, Switzerland.


BTK inhibitors have revolutionized the treatment of CLL. However, although patients (pts) above 80 years of age represent roughly 20% of the general CLL population, they remain underrepresented in clinical trials. Comorbidities, frailty, and organ dysfunction have a high prevalence in older pts and significantly impact the efficacy and tolerability of treatments as well as survival. The CLL-Frail trial aims to evaluate the efficacy and safety of acalabrutinib monotherapy in pts ≥80 years of age and/or a FRAIL scale score of ≥3.

Methods and Participants:

Patients needing treatment with previously treated and untreated CLL and ≥80 years of age and/or a FRAIL scale score ≥3 were eligible. A maximum of one previous therapy was allowed. At least 50% of patients needed to fulfill frailty criteria. Pts received acalabrutinib 100 mg BID until progression or intolerance. The primary endpoint was the overall response rate at the initial response assessment (cycle 7, day 1 = ∼6 months after initiation of therapy.


  • 30 pts were enrolled in the first 12 months of recruitment.
  • The median age was 82, and 50% had a FRAIL scale score of ≥3.
  • The median CIRS score was 10, with 73% of pts scoring>6.
  • The median ECOG-Score was 1.
  • Most pts had a Binet stage A (77%).
  • Unmutated IGHV and TP53mut/del were present in 63% and 10%, respectively.
  • 19 pts (63%) were treatment naïve.
  • In the previously treated cohort, prior lines of treatment included chemoimmunotherapy in 73% and ibrutinib + obinutuzumab + venetoclax, bendamustine + ibrutinib + ofatumumab, and obinutuzumab + venetoclax, in 9% of pts each.
  • At the data cut in November 2022, the median observation time was eight months, and 21 patients remained on therapy.
  • The reasons for discontinuation were adverse events in five (56%) and death and withdrawn consent in two (22%) patients each, respectively.
  • All patients experienced at least one AE, totaling 200 AEs, of which 35 (18%) were grade >3 (more serious).
  • Fifteen severe adverse events (SAEs) were reported, of which eight (53%) were assessed as treatment-related by the investigator.
  • There were no cases of severe (Grade ≥3) bleeding,
  • Two patients (6%) experienced atrial fibrillation with grades two and three, respectively.
  • Two cardiac SAEs termed cardiac failure were reported in patients with prior hypertension and atrial fibrillation.
  • Four patients (13%) died, of which one death was deemed treatment-related. Causes of death were infection in three cases (one bacterial and two COVID-19 pneumonia) and concomitant disease in one case.


Acalabrutinib seems well tolerated in an older and frail population, a group too often excluded in clinical trials.

Links and Resources:

Watch Dr. Brian Koffman’s monologue on the abstract:

The actual ICML abstract can be accessed by clicking: Safety of acalabrutinib treatment in very old (≥80 y) and/or frail patients with chronic lymphocytic leukemia – interim safety analysis of the ongoing phase II CLL-Frail trial

Stay Strong; We are all in this together

Brian Koffman, MDCM (retired), MSEd
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society, Inc.