A 2017 update on CLL management

This study reviewed recent evidence on the management of chronic lymphocytic leukemia (CLL).

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 diagnosis ranges from 67 to 72 years. Standard therapy for CLL usually involves a combination of chemotherapies and immunotherapies. Chemotherapy drugs kill or slow the growth of cancer cells. Immunotherapy uses agents that stimulate or restore the ability of the immune system to fight cancer.

Certain genetic abnormalities, such as damaged or missing parts in chromosomes, can make CLL more difficult to treat. These include deletions on 13q14, deletions on 11q, deletions on 17p, trisomy 12, and mutations of the TP53 gene.

Patients at different disease stages also have different treatment needs. The most common staging systems are called Rai and Binet. Both use physical examinations and blood counts to group patients from low-stage to advanced-stage disease. A more inclusive prognostic score (known as CLL-IPI) uses genetic, biological, and clinical variables to classify patients from low to very high risk.

This review outlines the current treatment options for CLL.

Some of the most notable advances in CLL treatment have been achieved by combining different types of therapies. For physically fit patients, chemo-immunotherapy with fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab (Rituxan) (also called FCR) remains the current standard therapy. In a study of 817 patients, 92.8% of patients treated with FCR showed overall response. The complete response rate was 44.5%. 76.6% of patients treated with FCR were progression-free at 2 years. However, FCR did not improve the survival of patients with deletion 17p.

The combination of bendamustine (Treanda) and rituximab (also called BR) has also been shown to be effective in relapsed CLL as well as newly diagnosed CLL. When used as a first-line treatment, the overall response rate to BR was 88%. Another study found reported an overall response rate of 45.5% in patients no longer responding to fludarabine. 59% of relapsed patients responded to BR. 92.3% of patients with deletion 11q, 100% with trisomy 12, and 7.1% with deletion 17p responded to BR.

Some elderly patients and patients with additional medical conditions may not tolerate standard therapy. Encouraging results have been reported when combining the milder chemotherapy drug chlorambucil (Leukeran) with an anti-CD20 antibody such as obinutuzumab (Gazyva), ofatumumab (Arzerra), or rituximab. One study examined chlorambucil plus ofatumumab in 447 newly diagnosed CLL patients not able to receive fludarabine-based treatment. The average time to disease progression was 22.4 months. This was significantly longer compared to chlorambucil alone (13.1 months). 50% of patients experienced serious side effects. An alternative for unfit patients is continuous therapy with the tyrosine kinase inhibitor ibrutinib (Imbruvica). One study noted a 12-month overall survival (time from treatment until death from any cause) rate of 90% in high-risk elderly CLL patients.

In cases of a disease relapse, the same treatment that induced a remission may be repeated as long as the duration of the remission was at least 3 years. If the disease relapses earlier, more intensive therapy is recommended. Treatment options include BR, alemtuzumab (Campath), lenalidomide (Revlimid), ofatumumab, ibrutinib, idelalisib (Zydelig), or venetoclax (Venclexta). The choice of one of these options may depend on the fitness of the patient and disease stage. Physically fit patients no longer responding to standard therapies or patients with deletion 17p may be offered a stem cell transplantation from a donor plus a kinase inhibitor or another novel agent. 

This study concluded that CLL can have a highly variable clinical course and a treatment regime should be matched to the patient’s characteristics, disease stage, and risk group.