Newer treatment options for CLL

This study reviewed the current treatment options for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common form of leukemia in Western countries. Treatment options for CLL depend on the stage of the disease (the severity) and the overall health and fitness of the patient. Patients with early-stage CLL who are not experiencing symptoms may follow a watch-and-wait method of management. Patients with stages III or IV or those with symptoms should receive treatment. Symptoms include greatly enlarged spleen or lymph nodes, rapidly increasing levels of lymphocytes (a type of white blood cell), weight loss, fever, or night sweats. The type of treatment depends on patient characteristics.

This review outlined different treatment options for CLL.

The standard first treatment for physically fit patients is a combination of the chemotherapies fludarabine (Fludara) and cyclophosphamide (Cytoxan) with the immunotherapy rituximab (Rituxan). One trial noted that 69% of patients were still alive 4.9 years after treatment, compared to 62% of patients treated with only chemotherapy. Another study noted a 6-year survival rate of 77%. This treatment combination has been associated with decreased white blood cell levels and a high rate of infections. Decreasing the dose of FCR or substituting other treatments for the chemotherapies are less toxic but also less effective.

Older patients with other health problems are generally treated with the chemotherapy chlorambucil (Leukeren). Recent studies have shown that combining this treatment with obinutuzumab (Gazyva) or rituximab improved response rates. Time to disease progression was longest with obinutuzumab (29 months) compared to rituximab (15 months) or chlorambucil alone (11 months). The addition of immunotherapies increased the rate of low white blood cell levels. Patients with few health problems may be treated with a reduced dose of FCR. Bendamustine (Treanda) and rituximab are also possible for fit patients over the age of 65.

Patients with certain genetic alterations (such as deletion 17p or TP53 mutation) are not as sensitive to chemotherapy. In these patients, ibrutinib (Imbruvica) or idelalisib (Zydelig) combined with rituximab or ofatumumab (Arzerra) improved response rates. Stem cell transplantation is an option for younger patients.

Treatment of relapsed CLL depends on when the patient relapses. In early relapse, ibrutinib led to a response in 90% of patients. 69% were still in remission (no disease activity) after 30 months. Idelalisib combined with rituximab also improved survival compared to rituximab alone.

In patients who relapse after 24–36 months, retreatment with chemotherapy and immunotherapy is possible. A combination of bendamustine, rituximab, and ibrutinib may be an alternative.

Studies are examining future treatment options, such as the sequential triple-T. This is targeted, tailored treatment, with chemotherapy to decrease tumor size, followed by targeted immunotherapy and long-term maintenance therapy. These treatments can be tailored to fit a patients’ fitness and response.

This study reviewed the treatment options for patients with different levels of health and fitness.