IgVH and Other High-Risk Cytogenetic Risk Factors in CLL

Ian W. Flinn, MD, PhD:Personally, in addition to the testing that the patient had, I would have ordered a next-generation sequencing panel. There are very limited panels, which have genes that are most relevant in CLL [chronic lymphocytic leukemia], such asp53,ATM, andMYD88.

But there are also much more broader panels available to physicians and their patients. Frankly, either is fine as long as you get those core genes. They’re important because we miss many of the alterations that are seen just with FISH [fluorescence in situ hybridization].

FISH picks up huge deletions in a chromosome, but approximately an equal number of patients who have 17p deletions will also have an intact chromosome but have mutations in thep53gene, which leads to dysfunction and similar outcomes.

This patient had high-risk chronic lymphocytic leukemia. First of all, he was symptomatic. He was technically, at this point, Rai stage I disease because he did not have a hemoglobin count of less than 11 g/dL. But he was borderline on that. He had some high-risk cytogenetics, with 11q deletion, which—for most patients who are treated with classical chemotherapy—has a worse survival and worse progression-free survival. Finally, he had an unmutated immunoglobulin heavy chain. We know that patients with an unmutated immunoglobulin heavy chain have a worse prognosis in terms of progression-free survival and overall survival.

These cytogenetic risk factors are important in determining a patient’s therapy. Until very recently, chemoimmunotherapy was the frontline therapy for most patients with CLL. These factors would have shown that a patient treated with chemoimmunotherapy would not do as well as a patient who does not have these risk factors. Now with the advancement to more targeted therapy in the frontline setting, some of these risk factors are overcome either completely or partially. That’s 1 reason why patients with these risk factors should probably be treated with a targeted therapy such as a BTK [Bruton tyrosine kinase] inhibitor.

Transcript edited for clarity.

Case:A 62-Year—Old Male WithIgVH-Unmutated CLL

• A 62-year-old male presented to PCP with complaints of extreme fatigue and night sweats
• PE: Enlarged mobile lymph nodes bilaterally (~1.5 cm), no palpable spleen or liver
• Laboratory findings:
  • WBC; 100 X 10⁹/L
  • Lymphocytes; 82 X 10⁹/L
  • Hb; 11.2 g/dL
  • Platelets; 190 X 10⁹/L
  • ANC; 1,950/mm³
  • LDH 150 U/L
• Cytogenetic; del(11q),IgVH-unmutated
• β2M, 2.9 mg/L
• Referred to community oncology who diagnosed patient with chronic lymphocytic leukemia
• Patient was started on ibrutinib + rituximab (IR)
• Rai Stage I