Clinical Management of Relapsed CLL - Episode 1

Diagnostic Workup and Risk Status for CLL

Danielle Brander, MD:So, this is a 70-year-old female with a known diagnosis of CLL who had progression by elevated white blood cell count and also some anemia, and was also, importantly, symptomatic by her progressive splenomegaly, and therefore, was presenting for a discussion of treatment. Her important prognostic markers that were tested included a FISH showing a deletion of 17p, anIgHVstatus showing unmutated.

The diagnostic workup for CLL, particularly for patients who require treatment, includes prognostic markers that no longer only allow us to define how long the patient would respond to treatment or how long till they need treatment, but we’re using these prognostic markers to determine the best course of action for CLL treatment. In this case, some of the markers that are critically important include the FISH test. FISH will test for deletion of 17p. I also, for patients starting treatment, checkTP53mutation status, as bothTP53mutations and deletion of 17p require a non-chemotherapy approach to the first-line treatment.

The risk status for this patient would be considered high to very high because she was found to have a deletion of 17p prior to any therapy.

This patient does require therapy by iwCLL treatment indications for a few reasons. First, she’s symptomatic by her splenomegaly. That is, she’s having left upper quadrant pains and has an enlarged spleen. The second reason that she would require treatment is that her anemia was reported as progressive. And now, 10 g/dl is less than the threshold where we consider requiring treatment.

There are many factors that I consider for each patient that requires treatment of their disease. Some of them are the patient’s age and other organ functions. Especially with chemotherapy, the creatinine and their kidney function is critically important. The other factors that you consider is just how the patient’s overall health status is. The average age, or the median age, of CLL diagnosis is around 72. So, many of these patients are older and do have other medical conditions that have to be taken into account.

Even with those factors considered, there are other key factors about the CLL that we take into account, and that’s why it’s important that these markers are checked ahead of time. The very key ones are the presence of theTP53dysregulation or dysfunction, and that can occur either through deletion of 17p or mutation of theTP53gene, and that is why it’s critical to test those 2 factors.

Patients who have those really should be considered for nonstandard chemoimmunotherapy approaches. And that is because there’s a lot of evidence that deletion of 17p orTP53mutation, those patients not only will not have a great response to chemotherapy, they also don’t have a long duration of response. And finally, there’s evidence that those patients are more prone to clonal evolution or change of their disease when the chemotherapy is given.

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