A 79-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia - Episode 1

High-Risk Chronic Lymphocytic Leukemia

Jeff Sharman, MD: Hello, my name is Jeff Sharman. I’m the Medical Director of Hematology Research for US Oncology, and I am a practicing oncologist at the Willamette Valley Cancer in Eugene, Oregon.

Today I’ve been asked to present a case of a 79-year-old gentleman with relapsed chronic lymphocytic leukemia to address some of the treatment considerations we have in this patient population.

This particular patient is a hypothetical patient but referred to me. We’ll say that he was a 79-year-old gentleman who initially presented to his outside medical oncologist for the first time complaining of some vague intermittent abdominal pain and progressive fatigue. His past medical history is notable primarily for medically-controlled hypertension. He had a myocardial infarction 8 years ago and is on low-dose aspirin. His original CLL diagnosis was about 7 years ago, and after a period of watchful waiting, he had progressive lymphocytosis and adenopathy. He was treated with ibrutinib 420 mg daily, his symptoms improved, and he achieved a stable disease with resolution of lymphadenopathy.

Unfortunately, after 5 years of disease control on ibrutinib, he complained of increasing fatigue and decreasing appetite. Upon physical exam, he had a return of palpable lymphadenopathy, and his spleen was palpable, 4 centimeters below the costal margin. At that time, seen by an outside medical oncologist, he was started on rituximab monotherapy due to his medical comorbidities, but after 6 months on this regimen, he presents to my clinic after moving to be closer to family.

His physical exam was notable this time for palpable bilateral cervical adenopathy, right-sided inguinal adenopathy. Labs showed a white blood cell count of 55,000, predominately lymphocytes, and neutrophil count of 3100. He was anemic and thrombocytopenic, with a hemoglobin of 9.4 and platelets of 90,000, respectively. His beta-2 microglobulin was elevated, and, notably, he had a creatine clearance of just 31 mL per min.

Flow cytometry confirmed the typical immunophenotype for CLL, and at this time, FISH testing was performed and, importantly, returned a deletion of 17p in a high fraction of the cells. He was Rai stage 4 with an ECOG performance status of 1. At this time, treatment was initiated with idelalisib in combination with rituximab, or I should say idelalisib was added to rituximab at this time, 150 mg PO BID.

Now this is an interesting case, and it presents a number of features that are challenging in terms of how to pick therapy in this population with significant comorbidities. I’ve been asked to address questions pertaining to both his prior management, his current situation, and so forth.

The first question I’ve been asked is to describe my initial impression of the case and what the prognosis was for this patient. You know this is a patient who has high-risk CLL. He has relapsed after ibrutinib, and he has a deletion of 17p. What that means is that chemoimmunotherapy is not going to work for this individual, so you really don’t have that much in the way of options. Then you’ve exhausted BTK inhibitors, and there’s a question of what you have left.

In this particular case, the outside provider used rituximab monotherapy probably for lack of clarity in what options might have been available; this is a patient that because of his age and comorbidities, it’s very possible this patient may ultimately pass away of their CLL, which, in contemporary CLL management, seems like a relatively rare occurrence.

When we discuss risk stratification for patients with chronic lymphocytic leukemia, there’s a couple of things that are really important. We think about their IgHV status, which is really a measurement of how quickly the CLL is growing. What are the kinetics of growth? Then we think about the FISH status, which is how resistant it is to therapy. Deletion of 17p is a particularly noteworthy abnormality because patients with 17p have very brief responses to chemoimmunotherapy-based approaches.

Similarly, we’re seeing updates with targeted therapy, such as venetoclax, that 17p can retain adverse prognostic significance in this population. In this particular patient’s case, idelalisib had been added to the regimen. It’s noteworthy that idelalisib outcomes appear to be independent of 17p, so whether 17p is present or not, the outcomes relative to 17p don’t matter quite as much.

Transcript edited for clarity.


Case: A 79-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia

Initial presentation

  • A 79-year-old man presented to a new medical oncologist for the first time complaining of vague intermitted abdominal pain, and progressive fatigue
  • PMH:
    • Hypertension, medically controlled
    • MI, 8 years ago, on 81 mg aspirin
    • CLL, diagnosed 7 years ago
    • After a period of watchful waiting he began treatment with ibrutinib 420 mg PO qDay; symptoms improved and achieved stable disease, resolution of lymphadenopathy
    • After 5 years of disease control on ibrutinib he complained of increasing fatigue and decreased appetite, on physical exam there was return of palpable lymphadenopathy; spleen was palpable ~4 cm below costal margin
    • He was started on rituximab
    • Currently after 6 months on rituximab monotherapy he presents to the clinic
  • PE: palpable bilateral cervical and right-sided inguinal lymphadenopathy

Clinical workup

  • Labs: WBC 55,000, lymphocyte 82%, ANC 3100/mm3, Hb 9.4 g/dL, plt 90 x 109/L, LDH 220 U/L, Beta-2-microglobulin 3.9 mg/L; creatinine clearance 31 mL/min
  • FC CD 5+, CD19+, CD20+ monoclonal B-cell population
  • FISH: CLL probe set tested, deletion 17p
  • IgHV mutational status: unmutated
  • Rai stage IV; ECOG PS 1
  • Treatment of idelalisib 150 mg PO BID was added to rituximab