Considering Additional Molecular Testing for CLL

Danielle Brander, MD:So, this patient who was started on frontline ibrutinib as part of a clinical trial initially did very well. She had response in her symptoms. The left upper quadrant pain went away, her palpable spleen went away, and by about 18 months on therapy she achieved complete response by exam and was feeling well.

However, she had developed atrial fibrillation as a complication associated with the ibrutinib, and despite multiple interventions and working with the cardiologist, she was unable to continue on the ibrutinib. And then by the spring of 2017, she had to stop the treatment. Though she did OK for a couple months, pretty quickly and expectedly she progressed again both in her possible splenomegaly and symptoms, as well as her cytopenias. And at that point, she returned to discuss next lines of treatment.

At that time in discussing her treatment options and, importantly, considering that she had the deletion of 17p, we repeated her organ function and with a normal creatinine elected to start the patient on venetoclax-based therapy.

When patients with CLL who are treated with frontline therapy and then relapse, in general, I recommend repeating the FISH panel. And the reason for this is for patients who don’t have 17p at the time of diagnosis, often we can see that change when they present with relapsed disease. I also recommend checking a full panel of chromosomes or karyotype, as we’re increasingly recognizing the patients who have complex karyotype overall and have a lower duration of response to some of the targeted therapies. However, we know this patient had a deletion of 17p on their FISH panel. I would still recommend repeating and checking for a complex karyotype. At this time, we don’t have a full understanding of the other prognostic markers that may be important in understanding the duration of response to venetoclax.

Transcript edited for clarity.

Case: An Older Patient with Relapsed CLL

March 2015

• A 70-year-old female reported symptoms of weight loss, fatigue, and pain in the upper left portion of her abdomen
• PE showed moderate axillary lymphadenopathy and splenomegaly, spleen palpated 7 cm below the costal margin
• Otherwise, the patient is overall well-appearing and continues to exercise
• Laboratory results:
  • WBC, 48,000; 73% lymphocytes
  • Hb, 10 g/dL (1 year ago Hb, 12 m/dL)
  • Platelets, 125,000/mm³(1 year ago platelets, 165,000/mm³)
  • ANC 1,800/mm³(WNL)
  • LDH, 250 U/L
  • Beta-2-microglobulin, 4.2 µg/L
• Cytogenetics by FISH showed 17p deletion in 56%
• IgVH unmutated
• Bone marrow biopsy; diffuse infiltration by CLL
• The patient was enrolled in a clinical trial and was treated with ibrutinib 420 mg daily
• After 18 months, she achieved complete remission of her disease and resolution of her symptoms

November 2017

• The patient developed had developed atrial fibrillation and despite cardiology interventions could not restart ibrutinib
• During routine follow up, the patient reported increasing fatigue
• PE: cervical lymphadenopathy, ~4 cm; spleen, palpable 8 cm below the costal margin
• Normal kidney function
• Laboratory results:
  • ALC; 112,000 cells/mL
  • Hb; 10.8 g/dL
  • Platelets; 105,000 cells/mm³
• The patient was started on venetoclax