Recent Food and Drug Administration (FDA) approvals have changed the landscape of treatment for chronic lymphocytic leukemia (CLL). In a session at the 2016 National Comprehensive Cancer Network (NCCN) Annual Conference, Jeffrey Jones MD, MPH, Wexner Medical Center, The Ohio State University (Columbus), provided an update to attendees on how these new treatment options are affecting choices at the clinical level.
In particular, Dr Jones identified four agents recently approved or currently seeking approval by the FDA for patients with relapsed disease: ibrutinib, acalabrutinib, idelalisib, and duvelisib.
In the phase 3 RESONATE trial, ibrutinib successfully reduced the risk of disease progression by 78% and 75% in the full population of patients with CLL and in patients with CLL who harbored a p17 deletion, respectively, compared with ofatumumab. However, 10 cases of atrial fibrillation occurred in those receiving ibrutinib compared with only 1 case in the ofatumumab arm. In March 2016, based on data from the RESONATE-2 trial comparing ibrutinib with chlorambucil, ibrutinib was granted FDA approval as a frontline treatment for CLL. The NCCN has since recommended the use of ibrutinib only in patients who are frail, older than 70 years, or younger than 70 with significant comorbidities. Dr Jones emphasized that chemotherapy should still remain the standard of care for patients younger than 70 due to the higher toxicity associated with ibrutinib and questions surrounding its long-term effects.
Acalabrutinib also demonstrated activity in CLL, generating a 95% response rate and durable remissions with a favorable safety profile. Dr Jones suggested that the adverse side effects associated with ibrutinib could be kinase-related and thus mitigated through the use of a tyronsine kinase inhibitor such as acalabrutinib.
Another drug Dr Jones discussed was idelalisib, which was found to reduce the risk of disease progression by 73% while extending progression-free survival by more than 8 months compared with ofatumumab. In addition, diarrhea resulting from the use of idelalisib could be relatively easy to manage unless it presents later on, which could require that treatment be discontinued.
Lastly, Dr Jones discussed duvelisib, which has not been approved by the FDA but has demonstrated an objective response rate of 57% in early trials. Duvelisib, said Dr Jones, could end up being an effective and less toxic option than its predecessor.
Dr Jones concluded his session by acknowledging the challenges associated with changes in standard care and new drug approvals. As these new agents are added to NCCN guidelines, community doctors will need to work quickly to understand and adopt them into their practices.
