Disease Testing in Chronic Lymphocytic Leukemia

Jeff Sharman, MD: MRD testing at this point is prognostic; it tells you how likely a patient is to maintain their response. But to date, there’s nothing that tells us how to change therapy based on MRD status. There are studies coming that will potentially have MRD-adapted treatment decisions. Findings from those studies have not reported. MRD testing, therefore, really just helps us to understand the likelihood of length of a response.

With patients treated with BTK strategies, MRD isn’t so much a consideration. That’s primary amongst patients treated with venetoclax. We’re asked how accurately it predicts the risk of relapse and how widely is it being used. Well, again, following obinutuzumab-venetoclax, you can check MRD status. From the MURANO Study, which is a population of relapsed-refractory patients treated with obinutuzumab-venetoclax, you can stratify based upon MRD high, low, and negative. If you’re negative, chances are you’re going to maintain your response considerably longer than those patients who are low or high. Those patients are going to have relatively short durations of response.

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