Novel Targeted Agents For First-line CLL Treatment

A new influx of targeted agents combined with data concerning the efficacy and tolerability of chemoimmunotherapy regimens call into question the current standards of care for the treatment of chronic lymphocytic leukemia (CLL), according to a review published recently in Cancer Treatment Reviews.¹

The disease primarily affects elderly patients with a median age of diagnosis of 71.² A patient’s age, comorbidities, and any possible chromosomal aberrations should influence treatment decisions, as these factors can affect the course of the disease and its treatment.

Current Standards

“The management of patients with CLL is undergoing improvements, particularly due to novel therapies,” review author Tadeusz Robak, MD, of the department of hematology at Copernicus Memorial Hospital, Medical University of Lodz, Poland, told Cancer Therapy Advisor.

“Purine analogs based immuno-chemotherapy, particularly fludarabine combined with cyclophosphamide and rituximab (FCR), is still the standard of care for first-line therapy of younger fit patients. But its use in older co-morbid patients is limited, particularly due to high toxicity,” Dr Robak said. “Recently, in this patient population, chlorambucil and anti-CD20 monoclonal antibodies (rituximab, ofatumumab or obinutuzumab) are recommended as the first-line treatment.”

FCR is recommended for physically fit patients based on the results of the GCLLSG CLL8 (ClinicalTrials.gov Identifier: NCT00281918) trial, which showed the first-line FCR significantly improved progression-free survival compared with fludarabine and cyclophosphamide alone (median 56.8 vs 32.9 months). But FCR was also associated with myelosuppression, hematologic toxicity, and infections, and patients older than 65 experienced these effects more frequently and with greater severity.^3,4

A second study comparing first-line FCR to bendamustine and rituximab also showed an advantage for FCR, though no difference was observed among patients older than 65.⁵ Elderly patients who are physically fit are therefore recommended to undergo treatment with bendamustine and rituximab, a combination with fewer side effects but lower efficacy.

Among elderly patients with comorbidities, recent trials showed the efficacy of chlorambucil plus an anti-CD20 antibody such as obinutuzumab, ofatumumab, or rituximab. One trial showed that ofatumumab plus chlorambucil significantly improved progression-free survival, overall survival, and complete response compared with chlorambucil alone.⁶

Another study of chlorambucil plus an anti-CD20 antibody showed an increase in adverse events, suggesting a need for novel therapies to provide patients with improvements in efficacy and safety profiles.⁷