Treatment tips in CLL

Thursday, February 20, 2020

The million-dollar question in the treatment of chronic lymphocytic leukemia (CLL) is what to do after a patient relapses following treatment with venetoclax. Anthony Mato, MD, and Lindsey Roeker, MD, both of Memorial Sloan Kettering in New York, join podcast host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to explore the evidence about this question and to review the initial patient work-up and treatment strategies.

In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, discusses patients compliance and how clinician biases can influence compliance.

Practice points:

  • For patients with CLL with unmutated immunoglobulin variable heavy chain gene (IgVH), novel agents are the first therapy.
  • Evidence is limited about the best treatment approach after relapse on venetoclax.

* * *

Initial work-up in patients with CLL

  • The initial work-up for patients with CLL is often fluorescent in situ hybridization (FISH), looking for trisomy 12, as well as deletion of 13q, 17p, and 11q.
  • Next-generation sequencing is used to look for mutations in TP53 and IgVH mutational analysis is done to recognize whether a patient is mutated.
  • IgVH-mutated patients tend to respond better to therapy.

When to treat

  • Henry recommends the “if it bothers you, it bothers me” approach, noting that indications for treatment include fever, chills, night sweats, lumps and bumps in the neck, large liver and spleen, and high creatine.


  • If a patient is IgVH unmutated, that takes chemoimmunotherapy combinations off the table, regardless of whether the patient is young or fit. Instead, they are on a pathway to receive a novel agent as first therapy.
  • The choices for novel agents keep expanding. Some standards include ibrutinib plus or minus obinutuzumab, venetoclax plus obinutuzumab, and acalabrutinib plus or minus obinutuzumab.
  • Each of these combinations has different adverse event profiles and dose schedules. Patient preferences and comorbidities should drive decision making on novel combinations.


  • The million-dollar question: What is the best treatment following relapse on venetoclax?
  • The answer is unclear but there are generally two choices: Re-treat with the same regimen or switch to a Bruton’s tyrosine kinase (BTK) inhibitor.
  • There are limited data on re-treatment and emerging data on BTK inhibitors after venetoclax that points to success.

* * *

For more MDedge Podcasts, go to

Email the show:

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Podcast Participants

David Henry, MD
David Henry, MD, FACP, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He received his bachelor’s degree from Princeton University and his MD from the University of Pennsylvania, then completed his internship, residency, and fellowship at the Hospital of the University of Pennsylvania. After 2 years as an attending in the U.S. Air Force, he was drawn to practicing as a hem-onc because of the close patient contact and interaction, and his belief that, win or lose with each patient, one can always make a difference in their care and lives. Follow Dr. Henry on Twitter: @davidhenrymd.
Ilana Yurkiewicz, MD
Ilana Yurkiewicz, MD, is a fellow in hematology and oncology at Stanford University, where she also completed her internal medicine residency. Dr. Yurkiewicz holds an MD from Harvard Medical School and a BS from Yale University. She went into hematology and oncology because of the high-stakes decision-making, meaningful relationships with patients, and opportunity to help people through some of the toughest challenges of their lives. Dr. Yurkiewicz is also a medical journalist. She is a former AAAS Mass Media Fellow and Scientific American blog columnist, and her writing has appeared in numerous media outlets including Hematology News, where she writes the monthly column Hard Questions. Dr. Yurkiewicz is on Twitter: @ilanayurkiewicz.