CLL: experts discuss workup and treatment strategies

  • David Henry, MD; Anthony R. Mato, MD; Lindsey Roeker, MD
  • 14 Apr 2020

  • curated by Pavankumar Kamat
  • Univadis Clinical Summaries
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  • In an interview hosted by David Henry, MD, of Pennsylvania Hospital in Philadelphia, 2 hematologic oncologists — Anthony R. Mato, MD, and Lindsey Roeker, MD, both of Memorial Sloan Kettering Cancer Center in New York — discuss treatment tips in chronic lymphocytic leukemia (CLL).

Key points

  • Workup:
    • Initial workup of CLL must also include fluorescence in situ hybridization, looking for trisomy 12 as well as deletions in 13q, 17p, and 11q.
    • Next-generation sequencing to determine TP53 mutations and IgVH mutational analysis is also important.
    • Mutated IgVH disease tends to respond a bit better to therapy.
  • Choice of the first treatment:
    • If the disease is IgVH unmutated, chemoimmunotherapy combinations are not considered, regardless of patient age or fitness.
    • A novel agent as the first therapy is suitable.
      • The standard option is ibrutinib plus or minus obinutuzumab.
      • There is also an option of time-limited (1 year) venetoclax plus obinutuzumab.
      • The third option is recently approved acalabrutinib with or without obinutuzumab.
  • Advice for using venetoclax:
    • For a patient with a white blood cell (WBC) count of 100,000 µL being considered for oral venetoclax, it is advisable to start with 20 mg and then have an escalation every 7 days. 
    • Sometimes high-risk patients need to be in-house for 48 hours once a week for the first couple of weeks, until their WBC count falls.
    • Debulking with obinutuzumab clears out a lot of the WBCs and potentially "melts away" some of the nodes.
    • Evidence shows a 36-month PFS of ~82% with 1 year of venetoclax therapy.
    • Ibrutinib and acalabrutinib are treat-to-progression approaches that appeal to patients who are unwilling to come to the hospital or do not want to consider an infusional-based therapy. 
  • Treating relapse:
    • In a patient with relapse, IgVH status is not likely to change, but TP53 mutational status can change.
    • For TP53-mutated disease treated with venetoclax with relapse after 3 years, it would be ideal to retreat with the same regimen or to switch to a Bruton's tyrosine kinase (BTK) inhibitor.
    • Emerging data indicate response rates exceeding 80% for BTK inhibitors after venetoclax.
    • Dr. Mato expressed no concerns with the use of a rituximab biosimilar, although he had not used one yet.