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A Study of Frontline Therapy in Adults 80 Years and Older with Chronic Lymphocytic Leukemia (CLL)

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Authored by Dr. Brian Koffman

The Bottom Line:

In those over 80 with chronic lymphocytic leukemia (CLL), older age and not being treated with a novel agent frontline were associated with increased mortality. The leading cause of death in this group was the CLL itself.

Who Performed the Research and Where Was it Presented:

Mazie Tsang led a group of researchers from the Mayo Clinic who presented their findings at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago in 2023.


While the average at the time of diagnosis is 71, those >80 years old are underrepresented in clinical trials, and there are less data on how they respond to therapy.

Methods and Participants:

The Mayo Clinic CLL Database was interrogated to study adults ≥80 years at the time of frontline CLL treatment between 1/1995 and 11/2022. Overall survival (OS), time to next treatment (TTNT), and cause of death were studied, and the study period covered years before and after the introduction of novel therapies.


  • 216 patients with CLL age ≥80 years at the time of frontline CLL therapy were studied.
  • The median time from CLL diagnosis to initiation of frontline therapy was 3.1 years.
  • The median OS after the start of frontline therapy was 3.9 years.
  • The median OS was:
    • 3.3 years for those who received alkylating agents (e.g., chlorambucil, n=96), a kind of chemotherapy,
    • 3.8 years for purine analogs (e.g., fludarabine, n=11), another kind of chemotherapy,
    • 3.9 years for anti-CD20 monoclonal antibody monotherapy (e.g., obinutuzumab, n=64),
    • Not reached for novel agents (n=43)
  • The types of novel agents included:
    • ibrutinib (n=19),
    • acalabrutinib (n=16),
    • venetoclax (n=7)
    • orelabrutinib (n=1).
  • Overall, survival was the same for the 36 patients who received a BTK inhibitor (ibrutinib, acalabrutinib, or orelabrutinib) compared to the seven patients who received venetoclax-based therapy.
  • At a median follow-up time of 6.7 years from the first visit, 143 patients died from the following:
    • progressive CLL (n=63),
    • infections (n=12),
    • other cancer (n=11),
    • non-CLL reasons (n=21).
    • Cause of death was unavailable for 36 patients.
  • Older age (any 5-year increase in age) was associated with a 50% increased risk of death.
  • Treatment with non-novel agents was associated with 3.2 times increased risk of death.
  • Of the 216 patients, 76 patients required second-line therapy.
  • The median time to the subsequent treatment (TTNT) was 4.2 years.


The novel agents, such as BTK inhibitors and venetoclax-based treatments, when used in the frontline setting, are associated with significantly improved overall survival in patients with CLL who are ≥80 years old. This is not surprising as it is the same outcome we see in younger patients.

The fact that 44% of these elderly patients died directly from the progression of their CLL belies the often-told maxim: You will die with your CLL, not from it. If it’s not true for nearly half of those in their 80s, how much more untrue is it for someone diagnosed at a younger age?

Links and Resources:

Watch my monologue on the ASCO abstract:

ASCO 2023: Chronic Lymphocytic Leukemia Treatment Options for Elderly Patients

To read the full ASCO article and see the tables, please click on A Study of Frontline Therapy in Adults >80 years with Chronic Lymphocytic Leukemia (CLL).

Stay strong. We are all in this together.


Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society, Inc.