First-line Treatment Options in CLL


A key opinion leader highlights alternative treatment options to ibrutinib in the first-line setting for chronic lymphocytic leukemia.

Andrew Zelenetz, MD: Are there alternatives to ibrutinib for the first line? There are. We have 2 head-to-head comparative trials in the relapse/refractory setting of ibrutinib vs acalabrutinib, and very recently presented was zanubrutinib vs ibrutinib. Both trials demonstrate at least equal efficacy of the 2 agents. There might be a hint of actually greater efficacy with zanubrutinib, but the data are way too preliminary to make any informed conclusions. One thing that’s clear is that the cardiovascular risks with both alternative agents, acalabrutinib and zanubrutinib, are lower. We see lower atrial fibrillation and lower hypertension. In a patient with preexisting hypertension, I’d shy away from starting with ibrutinib because patients with preexisting hypertension are at greater risk of having that exacerbated by ibrutinib. We don’t see that as much with acalabrutinib or zanubrutinib, for that matter.

Overall, this is a good patient for a single-agent BTK [Bruton tyrosine kinase] inhibitor. The alternative would be treatment along the CLL [chronic lymphocytic leukemia] 14 approach, with obinutuzumab and venetoclax. The advantage is that it’s a time-limited therapy vs an open-ended therapy. People are very comfortable with BTK inhibitors added as a totally appropriate first-line choice.

Now, BTK inhibitors are associated with different sets of adverse effects. All the approved drugs cause bruising and bleeding, and there’s no major difference in them. They all increase infection risk, and that’s because of their impact on the B-cell function. We see rash and diarrhea with all these agents as well. However, as I said, we see fewer cardiovascular effects with zanubrutinib and acalabrutinib, but we do we see them. You can still get atrial fibrillation with acalabrutinib because it’s not as though you can tell someone we’re going to give you this, and there’s no risk whatsoever.

This transcript has been edited for clarity.

Case: A 77-Year-Old Man With Chronic Lymphocytic Leukemia

Initial Presentation

  • A 77-year-old man presented to urgent care reporting worsening fatigue accompanied by persistent, unexplained fevers and night sweats over the past few weeks and unintentional 12-lb weight loss over the past 6 months
  • PMH: HTN, medically controlled; BPH; OA in spine and hips
  • PE: palpable cervical, axillary, and right-sided inguinal lymphadenopathy

Clinical Workup

  • Labs: WBC 49,000, lymphocyte 74%, ANC 3700/mm3, Hb 9.2 g/dL, PLT 90 x 109/L, LDH 240 U/L, B2M 4.1 mg/L
  • FC: CD 5+, CD23+, CD20+ monoclonal B-cell population; confirmed diagnosis of CLL

Hem/Onc Workup

  • Mutation testing: IGHV unmutated; FISH: positive for del(11q)
  • Rai stage IV; Binet stage C
  • ECOG PS 1


  • Started on treatment with ibrutinib 420 mg PO QD; his symptoms improved and he achieved partial response
  • 3 months into treatment he returned to urgent care reporting SOB, pain in his chest, confusion, and anxiety; he was convinced he was having a heart attack
    • Work-up revealed treatment-related atrial fibrillation
    • Situation was explained to the patient and he was offered medication and monitoring but preferred to change to a different medication out of concern for this happening again or worsening
    • Labs were repeated
  • Treatment was initiated with idelalisib 150 mg PO BID + rituximab
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