An overview of treatment options for older CLL patients

This study reviewed evidence on the treatment options for elderly patients with chronic lymphocytic leukemia (CLL). Authors summarized a number of treatment recommendations based on the results of clinical trials involving elderly CLL patients.

CLL is cancer of the blood and bone marrow. It is one of the most common types of leukemia in adults. The average age at time of diagnosis is around 70 years. Standard therapy for CLL usually involves a combination of chemotherapies and immunotherapies. Chemotherapy drugs kill or slow the growth of cancer cells. Immunotherapies stimulate or restore the ability of the immune system to fight cancer.

CLL usually progresses slowly. The majority of newly diagnosed patients will not need immediate treatment. Only patients with advanced disease or who are experiencing symptoms need treatment. Elderly patients and patients with additional medical conditions may prefer to delay treatment and its associated side effects. Recent advances in treatments have led to options that are easier to tolerate. 

The combination of fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab (Rituxan) (also called FCR) is considered the standard of care for CLL. FCR is only used in older patients with few other diseases who are physically fit. A recent study in younger CLL patients (average age 61 years) found that the combination of bendamustine (Treanda) and rituximab (also called BR) was less effective but easier to tolerate than FCR. In the subgroup of patients over 65, BR had a favorable risk to benefit profile. Another study examined BR in older patients (average age 72 years). BR led to an average time to disease progression of 40 months. This was significantly longer than when rituximab was combined with chlorambucil (Leukeran; average 30 months). The rate of side effects was also higher for BR (19% compared to 10%). Another study found the combination of bendamustine with a different immunotherapy drug, obinutuzumab (Gazyva), was effective for older CLL patients (average age 68 years). 32% of patients showed complete remission (no signs of disease).

Two studies reported good outcomes in older patients treated with the chemotherapy chlorambucil and antibody therapies. These patients were not able to be treated with FCR due to possible side effects. Adding rituximab to chlorambucil improved its effectiveness. Adding obinutuzumab further improved effectiveness. Time to disease progression with this combination (31 months) was significantly longer compared to chlorambucil alone (11 months). Importantly, the rate of serious side effects did not increase significantly. Serious infections were reported in 10 to 15% of patients. The second study reported similar results with the combination of ofatumumab plus chlorambucil in older patients.

Tyrosine kinase inhibitor therapy is a type of targeted therapy that blocks signals needed for tumors to grow. Two examples are ibrutinib (Imbruvica) and idelalisib (Zydelig). Ibrutinib has been associated with a low rate of side effects in older patients. The most common include diarrhea and fatigue. The RESONATE-2 trial reported improved time to disease progression and survival when ibrutinib was combined with chlorambucil. It was also effective in patients with CLL that is hard to treat, such as when there are certain genetic mutations. Two studies involving older CLL patients (average age 71 years) found that idelalisib plus rituximab was more effective than rituximab alone. However, the rate of side effects was higher in older patients. 42% experienced severe diarrhea. Immune system disorders (affecting the bowels, lungs, or liver) were also common. 

The authors made several recommendations for treating CLL in elderly patients. Fit older patients without many other medical conditions may be suitable to receive full-dose FCR. BR should be strongly considered as an alternative. Chemotherapy plus immunotherapy combinations involving chlorambucil have also been shown to be a safe and effective alternative. Treatment with ibrutinib or idelalisib is another option for older patients, particularly if CLL is considered hard to treat, or in patients whose cancer has returned after remission.