Triggers to Initiate Treatment in Patients With CLL

Matthew S. Davids, MD, MMSc:Cytogenetics continue to play an important role in our initial treatment recommendations for patients with CLL [chronic lymphocytic leukemia]. The main branch point being whether the patients have deletion 17p or not. If patients have deletion 17p, we know that they’re not going to have a good response to chemoimmunotherapy, both in terms of depth of response and also durability of response.

So these are patients we should be considering for novel agent-based approaches. And right now the drug that’s approved in this setting is ibrutinib. Ibrutinib, as you probably know, is an oral BTK [Bruton tyrosine kinase] Inhibitor that tends to generally be well tolerated in patients, even older patients with CLL. So for most patients who have deletion 17p, ibrutinib will be the treatment of choice.

Despite all of the changes we have had in CLL therapies over the last few years, one thing that has not changed is the indications for therapy. This was recently revisited by the International Workshop on CLL [iwCLL] in 2018, and it published new guidelines about CLL. But they did not change the recommendations for initial treatment. So these continue to include patients who have progressive cytopenias, anemia or thrombocytopenia, which would give them Rai stage III or IV disease; patients with bulky organ-threatening lymphadenopathy or splenomegaly; and patients who have constitutional symptoms that are being driven by the CLL, and these can include things such as unintentional weight loss, progressive fatigue, or night sweats.

This patient meets multiple iwCLL criteria for treatment. Interestingly he does not meet the criteria based on his counts. There’s no anemia and the thrombocytopenia is mild. However, this patient has bulky lymphadenopathy and splenomegaly, and has developed significant constitutional symptoms, including progressive weight loss and fatigue. It’s always important to consider other causes of these symptoms in patients, because there are, of course, other malignancies and other causes of these constitutional symptoms, but in this particular patient, given the bulky lymphadenopathy and splenomegaly associated with constitutional symptoms, that certainly does warrant treatment by the iwCLL criteria.

Transcript edited for clarity.

Case:A 74-Year-Old Male WithIgVH-Unmutated CLL

• A 74-year-old male presented to PCP with complaints of extreme fatigue, weakness, and weight loss of ~15lbs over the last 3 months.
• PMH: Mild hypertension managed by statin
• PE: BP 135/85, enlarged lymph nodes (~6cm), palpable spleen approx. 7cm below costal margin
• Laboratory findings:
  • WBC; 100 X 10⁹/L
  • Lymphocytes; 82 X 10⁹/L
  • Hb; 15.1 g/dL
  • Platelets; 125 X 10⁹/L
  • ANC; 1,800/mm³
  • LDH 250 u/L
• β2M, 4.3 mg/L
• FISH; normal
• Molecular analysis;IgVH-,TP53wild-type
• ECOG PS 1
• Rai Stage II