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Treatment Tools in CLL
The Value of Interactive Tools in Selecting Treatment for CLL

Released: October 28, 2024

Expiration: October 27, 2025

Nicole Lamanna
Nicole Lamanna, MD
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Key Takeaways
  • Interactive decision support tools can impact HCP treatment decisions in a rapidly evolving therapeutic landscape, potentially improving patient care.

Numerous recent approvals of effective targeted and immune therapies have shifted treatment paradigms for chronic lymphocytic leukemia (CLL). A rapid pace of approvals and expanded indications can challenge oncology healthcare providers (HCPs) to make optimal treatment decisions. To provide HCPs with case-specific treatment recommendations from 5 CLL experts (including myself), Clinical Care Options (CCO) has developed and maintained an interactive treatment decision support tool. In this commentary, I will discuss the value of tools like these in assisting HCPs who are considering treatment options for their patients.

Using Interactive Treatment Decision Support Tools
For each version of the CLL tool, 5 experts provided treatment recommendations for hundreds of different case scenarios in the newly diagnosed and relapsed/refractory CLL settings (in this most recent iteration, Farrukh T. Awan, MD, MS, MBA; Jennifer R. Brown, MD, PhD; Sameer A. Parikh, MBBS; Jennifer A. Woyach, MD; and I provided expert guidance and recommendations). Unique case scenarios were defined by patient and disease factors that the experts considered critical to making treatment decisions, including patient age and fitness, cytogenetic abnormalities, and previous treatment. To use the tool online, HCPs can enter patient information and their intended treatment plan; expert recommendations for that specific patient scenario are then provided, followed by a survey to determine whether the recommendations will impact the HCP’s intended treatment.

Tools like these have been used extensively by HCPs treating patients with CLL. For example, with the latest version of the CLL tool (which was released August 20, 2024 and can be found at clinicaloptions.com/CLLtool), 130 HCPs have entered 225 CLL cases into the tool. Of those responding, 51% reported that they sought recommendations for a specific patient, and after reviewing expert recommendations for their cases, 52% of HCPs whose planned treatment differed from the experts’ treatment recommendation indicated that they would change their treatment. These data suggest that a decision support tool can impact HCP treatment decisions in a rapidly evolving therapeutic landscape, potentially improving patient care.

Treatment Recommendations for Specific CLL Cases
Let’s look at a few patient cases to illustrate the type of treatment recommendations the tool can provide. Our first case is an 80-year-old male with previously untreated CLL. He has bulky 7 x 7 cm bilateral axillary lymph nodes and 12 x 12 cm retroperitoneal and para-aortic nodes, along with significant chest lymphadenopathy. Worsening symptomatic anemia is observed, with a hemoglobin level of 8.9 g/dL. He has no evidence of hemolysis, and his platelet level is 90,000/µL with a white blood cell (WBC) count of 325,000/µL. Testing reveals his CLL to be IGHV unmutated, with normal findings with fluorescence in situ hybridization (FISH). He has a long-standing history of controlled hypertension and diabetes; he also has chronic renal insufficiency with creatinine  2.0 mg/dL.

By entering this patient’s key characteristics into the tool (newly diagnosed, no del(17p) or TP53 mutation, IGHV unmutated, bulky disease, and diminished creatinine clearance), we find that the experts would recommend acalabrutinib or zanubrutinib (3 experts) or venetoclax + obinutuzumab or acalabrutinib or zanubrutinib (2 experts). From my perspective, this patient’s case is complicated by bulky disease and a history of hypertension, diabetes, and chronic renal insufficiency. Treating him with venetoclax plus obinutuzumab could be considered with admission of the patient to the hospital for very close monitoring of his kidney function. Given his bulky disease and WBC count of 325,000/µL, he has a high risk of tumor lysis syndrome with venetoclax or obinutuzumab. I would consider using a second-generation BTK inhibitor like acalabrutinib or zanubrutinib for this patient, likely without an anti-CD20 monoclonal antibody (mAb). Given the favorable outcomes seen with second-generation BTK inhibitors in head‑to‑head trials with ibrutinib, I tend to recommend that new patients start with a second-generation BTK inhibitor like acalabrutinib or zanubrutinib when these agents are optimal for the patient. It would be important to work with other members of this patient’s care team, such as an internist or cardiologist, so that they would be aware that he might need adjustment in his hypertension medications with a second-generation BTK inhibitor.

Let’s look at another case. A 63‑year‑old man is newly diagnosed with CLL and presents to his primary care provider with lymph node swelling and increasing fatigue. He has a history of some hypertension, which is medically controlled, as well as atrial fibrillation. Upon examination, he is found to have axillary lymphadenopathy, and his spleen is not palpable. Laboratory results show progressive lymphocytosis, mild anemia with a hemoglobin level of 10.3 g/dL, and a platelet count of 107,000/µL. Analysis by FISH reveals that the patient has del(11q), and molecular analysis shows he has unmutated IGHV.

By entering this patient’s key characteristics into the tool (newly diagnosed, no del(17p) or TP53 mutation, IGHV unmutated, history of cardiac arrhythmias), we find that the experts would recommend venetoclax + obinutuzumab (4 experts) or acalabrutinib or zanubrutinib (1 expert). From my perspective, with this individual’s hypertension well controlled, treatment with a BTK inhibitor could be an option, although I would likely choose a second-generation BTK inhibitor for the more favorable toxicity profile. It’s also likely that you would need to adjust his other medications. If he’s on coumadin or another anticoagulant, or if you’re concerned about his history of atrial fibrillation and hypertension, venetoclax plus obinutuzumab would also be an option for this patient.

Let’s look at a last case of a 72-year-old man with CLL (unmutated IGHV, del(11q), and no TP53 mutation or del(17p) on molecular testing) who had previously been treated with venetoclax + obinutuzumab. He tolerated treatment well and completed 12 months of therapy, but after 3 years he experienced progressive disease with lymphocytosis, lymphadenopathy, and anemia. He was then treated with acalabrutinib, which he tolerated well, but 2 years later he now has slowly progressive symptomatic disease with a WBC count of 42 x 109/L, Hb 10.8 g/dL, and a platelet count of 90,000/µL. A FISH panel shows del(11q) and no del(17p) or TP53 mutation; however, mutation testing reveals a BTK C481 mutation.

By inputting the patient’s key characteristics into the tool (requires third-line therapy; received first-line venetoclax + anti-CD20 mAb with relapsed disease ≥2 years after completion of treatment; received second-line covalent BTK inhibitor–based therapy), we can note that the experts would recommend a noncovalent BTK inhibitor such as pirtobrutinib (3 experts), pirtobrutinib or lisocabtagene maraleucel CAR T-cell therapy (1 expert), or retreatment with venetoclax + obinutuzumab (1 expert).

Your Thoughts
What guidance do you use when making treatment decisions for patients with CLL? Have you used a treatment decision support tool when considering therapy? Try CCO’s CLL tool at clinicaloptions.com/CLLtool and leave a comment to join the conversation.

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Have you used an interactive decision support tool when considering treatment options for a patient with CLL?

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