Chronic Lymphocytic Leukemia

While the approval of new agents represents a great step forward in the treatment of chronic lymphocytic leukemia (CLL), physicians are now challenged with how to best utilize these new treatment options, according to a presentation by Anthony Mato, MD, MSCE, at the 2nd Annual Live Medical Crossfire: Hematologic Malignancies.

An updated analysis of obinutuzumab alone or in combination with chemotherapy for patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia detected no new safety signals. Investigators in the phase IIIb GREEN trial also found overall response rates greater than 80% at 3 months post-treatment in some patients.

According to long-term follow-up data from the phase III CLL11 study, treatment with obinutuzumab combined with chlorambucil reduced the risk of death by 24% versus rituximab plus chlorambucil in treatment-naïve patients with chronic lymphocytic leukemia with comorbidities. These findings were presented at the 2018 European Hematology Association Congress.

Neil E. Kay, MD, a professor of medicine at the Mayo Clinic, discusses the challenges that arise when treating a patient with relapsed chronic lymphocytic leukemia (CLL). Most times, responses in this setting are short lived.

Matthew S. Davids, MD, MMSc, discusses the findings with duvelisib plus fludarabine-cyclophosphamide-rituximab as a frontline therapy for younger patients with CLL, as well as the potential future for this agent in the treatment of patients with CLL.

Based on data from the phase III MURANO trial, venetoclax has been granted a regular approval by the FDA for the treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, with or without 17p deletion, who has received at least 1 prior therapy.

According to results presented at the 2018 ASCO Annual Meeting, moxetumomab pasudotox, a first-in-class recombinant immunotoxin targeting CD22, demonstrated deep and durable responses in a substantial proportion of pretreated patients with relapsed/refractory hairy cell leukemia.

Treatment-naive patients with chronic lymphocytic leukemia achieved high rates of minimal residual disease–negative status of 77% with peripheral blood testing after 6 cycles from treatment with ibrutinib (Imbruvica) and venetoclax (Venclexta). Additionally, patients in the CAPTIVATE trial, wihch was presented during the 2018 ASCO Annual Meeting, achieved an objective response rate of 100%.

Optimizing Targeted Therapy in IgVH-Unmutated CLL

According to topline results from the phase III ILLUMINATE trial, the combination of ibrutinib and obinutuzumab improved progression-free survival compared with chlorambucil plus obinutuzumab in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Neil E. Kay, MD, professor of medicine at the Mayo Clinic, addresses the “Big 4” in salvage therapies for patients with relapsed/refractory chronic lymphocytic leukemia, including a newer therapy coming down the pipeline now.

According to results from the MABLE trial, the combination of rituximab plus bendamustine demonstrated significant value as a frontline treatment option for fludarabine-ineligible patients with chronic lymphocytic leukemia.

Results from a recent study conducted at the University of Pennsylvania may demonstrate why some patients with chronic lymphocytic leukemia are resistant to tisagenlecleucel, while potentially providing a pathway to enhance patient response.

The combination of bendamustine and rituximab induced a 12-month progression-free survival of 78.6% for patients with chronic lymphocytic leukemia, suggesting that the combination is an effective first salvage regimen.

The FDA approved several indications throughout the month of April 2018. A number of drugs were granted priority review and Fast Track designation. The FDA also halted all clinical trials using tazemetostat as treatment, and new initiatives were introduced to help ease the development of genetic and genomic-based tests. Check out our list of all FDA happenings from April 2018.