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Key Considerations CLL Nurses
Key Considerations for Hematology/Oncology Nurses Managing CLL/SLL

Released: June 23, 2026

Amy Goodrich
Amy Goodrich, RN, MSN, CRNP
Mollie Moran
Mollie Moran, APRN-CNP
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Key Takeaways
  • One third of patients with CLL/SLL require treatment at diagnosis, one third will progress to treatment after a period of observation, and one third will never need to receive therapy.
  • Both covalent BTK inhibitors and BCL-2 inhibitors are effective first-line treatments for CLL/SLL and differ in goals of treatment, monitoring needs, and practical demands on patients. 
  • In relapsed/refractory CLL/SLL, pirtobrutinib is an important noncovalent BTK inhibitor option now approved for patients who progressed following previous covalent BTK inhibitor therapy.
  • Proactive patient education about expected adverse events can support adherence to therapy.

The treatment landscape for chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL) has shifted away from chemoimmunotherapy and toward targeted therapy selected based on disease biology and patient goals, preferences, and resources. For hematology/oncology nurses, the expanding number of options has made patient education more nuanced. Patients need to understand not only why therapy is being recommended, but also why treatment may be deferred, why a specific regimen may be preferred over another, and how early reporting of adverse events (AEs) can help them remain on effective therapy. In this commentary, Amy Goodrich, RN, MSN, CRNP, and Mollie Moran, APRN-CNP, provide an overview of the treatment approaches for CLL/SLL with key considerations for nurses. You can find more in-depth information in this on-demand webinar, accompanying slides, and quick PDF guide.

Diagnosis and Prognosis of CLL/SLL

Mollie Moran, APRN-CNP: As many hematology and oncology nurses know, CLL/SLL is the most common leukemia in the Western world. It is a chronic, generally incurable mature B-cell neoplasm, with CLL being more apparent in the blood and SLL more apparent in the lymph nodes or spleen. Most patients are asymptomatic and are most often diagnosed through routine blood work. Approximately one third of patients will require treatment at diagnosis, with two thirds undergoing observation and half of those observed initially will require treatment as their disease progresses. We call observation watch-and-wait, although many patients experience it as “watch-and-worry”. It can be challenging for patients to grasp that they do not need immediate treatment, but monitoring is an active method of clinical management and data show that 5-year survival rates for newly diagnosed patients are nearly 90%. Even if they do need future treatment, we can reassure them that there are many highly effective and well-tolerated options.

At diagnosis, a baseline risk assessment helps to estimate when they will need treatment, what type of treatment they will require, and how well they may respond. Unfavorable prognostic markers include TP53 mutation, del(17p), unmutated IGHV, and del(11q). Favorable features include mutated IGHV and del(13q) as the sole abnormality, and normal cytogenetics and trisomy 12 are generally considered neutral.

When to Initiate Treatment

Mollie Moran, APRN-CNP: CLL/SLL is treated when patients meet 1 of several indications. First, we should investigate if they are eligible for a clinical trial regardless of whether they are experiencing symptoms. Another indication is any significant disease-related symptoms such as severe fatigue, unintentional weight loss of at least 10% over the last 6 months not related to a GLP-1 therapy, drenching night sweats, or fever without infection. Progressive, symptomatic, or bulky lymphadenopathy; and splenomegaly causing a feeling of abdominal fullness or early satiety are also indications for treatment.

CLL is present in the peripheral blood, so treatment is also necessary when other organs are involved, such as threatened end-organ function, progressive thrombocytopenia, steroid-refractory autoimmune cytopenias, or progressive anemia. A rising white blood cell count alone is not the indication for therapy as patients with CLL can live with a very high white blood cell count for a long period without requiring intervention.

Considerations for Frontline Treatment Selection

Amy Goodrich, RN, MSN, CRNP: When we do decide to treat, recommended frontline therapy is stratified by the presence or absence of del(17p) or TP53 mutation. Targeted treatments have overwhelmingly become preferred over chemoimmunotherapy. We have fixed-duration and measurable residual disease–guided regimens containing the BCL-2 inhibitor venetoclax and continuous covalent BTK inhibitor–based regimens. The second-generation BTK inhibitors, acalabrutinib and zanubrutinib, have proven to be at least as efficacious as the first-generation inhibitor ibrutinib with fewer AEs, so ibrutinib is now rarely used in the frontline setting.

Treatment selection requires shared decision-making as there are several patient-specific factors to consider, including comorbidities, potential drug interactions, disease presentation, as well as AE profiles and treatment administration of the different options. For instance, oral BTK inhibitors have the convenience of no infusions and no regular monitoring for tumor lysis syndrome (TLS), a serious AE of venetoclax. So, for a patient with a long commute from the clinic and time-consuming responsibilities at home, continuous oral BTK inhibitor–based treatment may be the best option to minimize clinic visits. However, cardiac comorbidities or concerns about long-term adherence may have us more often considering venetoclax with obinutuzumab.

It is also important to discuss with patients the differing goals of fixed-duration and continuous therapy. With continuous therapy, we aim for disease control and prolonged progression-free survival rather than deep remission. Treatment continues as long as it is effective and tolerated; however, disease will likely still be detectable. Alternatively, fixed-duration venetoclax-based therapy aims for deeper remissions, often with undetectable measurable residual disease and treatment-free remission. Both are reasonable approaches and the choice is dependent on patient preferences.

Enter your patient’s clinical presentation into this interactive treatment decision tool to receive expert recommendations for the frontline treatment of CLL/SLL.

Sequencing Treatment for Relapsed/Refractory CLL/SLL

Mollie Moran, APRN-CNP: Our treatment approaches have been evolving as we see more patients with CLL/SLL treated with novel targeted agents, and we know that not all relapses are created equally. If their disease progresses after treatment, we repeat FISH and cytogenetic testing to identify del(17p) and TP53 mutation as well as possibly BTK and PLCG2 mutations, like mutations to BTK C481S, to identify specific mechanisms of resistance to treatment. However, it is important to remember that IGHV mutation status does not change after initial testing.

For second-line therapy, it is common to alternate BTK inhibitors and venetoclax as they have different targets and side effect profiles. There are also some data that treating patients with a BTK inhibitor before venetoclax can decrease tumor burden and therefore reduce risk of TLS with the subsequent BCL2 inhibitor.

For heavily pretreated or double-refractory patients with CLL/SLL, noncovalent BTK inhibitors have an important role after covalent BTK inhibitor exposure. Ibrutinib, acalabrutinib, and zanubrutinib bind covalently to BTK in the ATP pocket at the C481 site; thus, C481S mutations can impair binding and cause resistance to the entire drug class. Alternatively, pirtobrutinib is a noncovalent BTK inhibitor that does not depend on binding to the C481 site and has an AE profile similar to that of the covalent BTK inhibitors but with a generally decreased incidence. It was originally approved by the FDA for the treatment of adults with R/R CLL/SLL after 2 prior lines of therapy, including a BTK inhibitor and BCL2 inhibitor. However, pirtobrutinib recently received expanded approval after prior treatment with a covalent BTK inhibitor alone, with prior venetoclax exposure no longer being required. There were also recent data from the BRUIN CLL-322 study that showed the addition of pirtobrutinib to fixed-duration venetoclax and rituximab improved outcomes for R/R CLL/SLL after at least 1 prior line of therapy. As a result of these developments, we may see pirtobrutinib used more frequently in the second line.

Lisocabtagene maraleucel, an autologous CAR T-cell therapy, is another treatment option for R/R CLL/SLL in the third-line setting. CAR T-cell therapy requires monitoring for a variety of AEs, most notably cytokine release syndrome and neurotoxicity, but it is a useful treatment option that is moving further into the outpatient setting. Pirtobrutinib is often used before CAR T-cell therapy, but it can also be used as a bridging therapy to lisocabtagene maraleucel.

Managing AEs and Supporting Treatment Adherence

Amy Goodrich, RN, MSN, CRNP: Patient education on potential AEs should begin before treatment starts because expected toxicities are less likely to interrupt therapy when patients know what to report and how symptoms can be managed.

BTK inhibitor toxicities of special interest include cardiac events like atrial fibrillation and ventricular arrhythmias, as well as bleeding, hypertension, and infections. Patient education regarding bruising and bleeding is particularly important as these AEs can easily occur in day-to-day life and can be serious. Other common events include anemia, arthralgia, myalgia, cough, diarrhea, fatigue, headache, and neutropenia. Lymphocytosis is also expected and patients should be warned that they will likely have an increased white blood cell count as treatment begins, but this is temporary and should eventually return to baseline. Some AEs can be managed with dose reductions or interruptions, but many can be easily managed with other treatments. For instance, headaches often occur early in treatment and can be improved with caffeine or acetaminophen; however, NSAIDs should be avoided due to risk of bleeding. Use this guide to receive expert recommendations for the management of BTK inhibitor AEs.

With venetoclax, AE counseling shifts toward TLS, infusion-related reactions, cytopenias, and infection risk. All patients should take allopurinol prior to treatment and should focus on staying hydrated each day. It should also be communicated that monitoring for TLS is important for safety and will be frequent.

Treatment adherence is going to be influenced by the tolerability of these agents as well as cost, patient support at home, and ability to travel to the clinic for IV infusions or ability to establish a routine for oral medications. Shared decision-making is crucial to helping patients feel more responsible for their care and be more adherent to these regimens.

Your Thoughts
What factors have you found to be most important to your patients when considering the available treatment options? What other topics related to the care of patients with CLL/SLL would you like to learn more about? Answer our poll or leave a question for our faculty in the comments.

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