Understanding Chronic Lymphocytic Leukemia: Treatment, AEs, and More


Understanding CLL is important for all oncology nurses, regardless if they specialize in hematologic or solid malignancies.

All nurses—whether treating solid tumors or hematologic malignancies–must better understand blood cancers, such as chronic lymphocytic leukemia (CLL), as well as their treatment options and special considerations associated with the disease, according to Laura J. Zitella, MS, RN, ACNP-BC, AOCN.

“Many of your patients, even those with solid tumors, are at risk for developing leukemia. So, [learning about leukemia] is applicable to [all nurses]. In addition to that, age is one of the biggest risk factors for leukemia. So, you might have a patient who has head and neck cancer but is possibly being treated for their CLL,” Zitella, a hematology/oncology nurse practitioner and associate professor at the University of California San Francisco, said during a presentation at the 3rd Annual School of Nursing Oncology.

Chronic Lymphocytic Leukemia

CLL is one of the most common adult leukemias, for which the majority of patients are diagnosed by routine exams or blood tests that find asymptomatic increases in lymphocyte count.

The disease is characterized by the proliferation of small, mature-appearing lymphocytes in the blood, marrow, and lymphoid tissue. Of note, more than 95% of cases in the US are B-cell CLL, Zitella said.

Clinical features of the disease include an absolute lymphocyte count of >5000/mcl with predominance of mature small lymphocytes, anemia and thrombocytopenia, lymphadenopathy, hepatosplenomegaly, hypogammaglobulinemia, and elevated Beta-2 microglobulin and lactate dehydrogenase.

To Treat or Not to Treat

Approximately 80% to 90% of patients are asymptomatic at the initial presentation of their diagnosis—for which standard of care is to simply observe the patient.

“There has been no survival benefit to early treatment (compared with watching and waiting) in asymptomatic patients,” Zitella explained.

Treatment comes into play when patients could be eligible for a clinical trial; if they experience significant disease-related symptoms, such as fatigue, night sweats, weight loss, or fever without infection; there is a risk of end-organ damage; there is bulky disease (spleen is >6 cm below costal margin or lymph nodes > 10 cm); lymphocytes doubled in 6 months or less; there are progressive cytopenias; or there is progressive high-risk disease.

Treatment Options

Treatment varies for patients with CLL, depending on their age, any comorbidities they may have, as well as if a patient presents with a 17p deletion.

“The most important thing in leukemias is knowing the genomic factors,” Zitella said. “This has been true for years even before it became important in solid tumors, so genetic factors have always been the defining characteristic of leukemias.”

Preferred options for patients who are you (aged 65 or younger) and fit are ibrutinib (Imbruvica) or a clinical trial as an initial therapy, or ibrutinib (if not used in the frontline setting), venetoclax (Venclexta) plus rituximab (Rituxan), duvelisib (Copiktra), or idelalisib (Zydelig) plus rituximab as relapsed therapies.

For young patients with comorbidities, those aged 65 or older, and individuals who are frail with significant comorbidities, oncologists will use ibrutinib, venetoclax plus obinutuzumab (Gazyva), or suggest a clinical trial in the first-line setting. For these patients who have relapsed, they may be treated with ibrutinib, venetoclax plus rituximab, duvelisib, or idelalisib plus rituximab.

For those with a 17p deletion, initial therapy consists of either ibrutinib, venetoclax plus obinutuzumab, or a clinical trial. In the relapsed setting, treatment includes ibrutinib (if not used in the frontline setting), venetoclax plus rituximab, duvelisib, idelalisib plus rituximab.

“There is a trend in leukemia towards moving toward nonchemotherapy-based regimens,” Zitella said. “You are going to see in CLL that all of the current preferred regimens recommended by the NCCN are all nonchemotherapy. So, that has been a really exciting advance.”

Adverse Events

With any treatment, there are a variety of adverse events (AEs) for nurses to keep in mind.

AEs associated with ibrutinib include diarrhea, hypertension, atrial fibrillation, bleeding, and rash. Hypersensitivity reactions and hepatitis B reactivation are commonly associated with both obinutuzumab and rituximab. Nurses should be take precautions for tumor lysis with venetoclax. And lastly, duvelisib and idelalisib are both associated with diarrhea, hepatotoxicity, pneumonitis, rash, cytomegalovirus reactivation, and pneumocystis pneumonia prophylaxis.

In addition, nurses should monitor for atypical infections, such as sinopulmonary infections; hypogammaglobulinemia; autoimmune hemolytic anemia and/or autoimmune thrombocytopenia; and non-melanomatous skin cancer.

Zitella recommended to nurses to reference the National Comprehensive Cancer Network guidelines to better understand various leukemias, their treatments and their AEs.

“My other tip about NCCN Guidelines is that if you read the patient guidelines, it is an excellent summary that is very easy to read about any disease,” she said. “So, when I am seeing something for the first time, that is one of the things that I use.”

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