Treatment Standards in Chronic Lymphocytic Leukemia

Effectively treating chronic lymphocytic leukemia (CLL) requires pharmacists to remain up-to-date on the latest advances in care, which was the subject of the continuing education session “Current and Emerging Treatment Standards for Patients With Chronic Lymphocytic Leukemia,” presented at the Asembia Specialty Pharmacy Summit 2018.

CLL is the most common form of the disease in Western countries, and in 2017, there were an estimated 20,110 new cases and 4660 deaths as a result of CLL. Novel immunotherapies target specific signaling pathways in CLL, such as Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3Kδ). The symposium provided a review of current and emerging agents and treatment regimens for CLL, along with communication strategies to improve decision making among health care providers and patients with CLL.

After a brief overview on CLL diagnosis, staging, and prognosis, the presentation provided pertinent clinical trial data and drug information on 2 BTK inhibitors, ibrutinib and acalabrutinib; an oral PI3Kδ inhibitor, idelalisib; and a B-cell lymphoma 2 (BCL-2) inhibitor, venetoclax. Newly updated 2018 National Comprehensive Cancer Network (NCCN) guidelines recommend ibrutinib, chlorambucil plus obinutuzumab, or fludarabine cyclophosphamide rituximab as a first-line option.

In the RESONATE-2 trial, ibrutinib demonstrated significant efficacy over chlorambucil in progression-free survival (PFS; HR, 0.16; 95% CI, 0.09-0.28; P<.001) and overall survival (HR, 0.16; 95% CI, 0.05-0.56; P = .001) in patients with relapsed/refractory CLL/small lymphocytic lymphoma, with fewer adverse events leading to study discontinuation (9% vs 23%). Acalabrutinib, another BTK inhibitor, is FDA approved for mantle cell lymphoma and recommended for relapsed CLL under “other recommended option.”

Acalabrutinib is currently undergoing phase 3 trials after demonstrating a median PFS of 88% (95% CI, 81%-93%) in a prior study. Idelalisib is an oral PI3Kδ inhibitor approved by the FDA for relapsed CLL with rituximab; however, this agent is not for first-line use, because of infection-related toxicity and deaths during phase 3 trials in previously untreated patients with CLL.

Venetoclax is a BCL-2 inhibitor approved by the FDA for relapsed CLL with 17p deletion, although the NCCN guidelines recommend this agent alongside rituximab in patients with or without 17p deletion. The interim analysis from the MURANO trial comparing venetoclax plus rituximab with bendamustine plus rituximab showed significantly longer PFS in venetoclax plus rituximab across all subgroups (1-year PFS, 92.7% vs 72.5%; 2-year PFS, 84.9% vs 36.3%).

In addition to reviewing notable clinical trial data and NCCN guideline recommendations, the presentation covered the management of immune-related adverse events, which is critical in the use of BTK inhibitors. Ibrutinib therapy is not very selective because it also affects alternative kinase targets that can compromise the therapeutic efficacy and may increase the risk of adverse events; the more selective BTK inhibitor, acalabrutinib, is anticipated to have similar efficacy with reduced toxicity.

The presentation concluded with a review of optimal patient communication strategies, including patient and caregiver education, development of a treatment plan, managed care concerns and economic considerations, strategies to improve adherence, and infection-related risks and prophylaxis