Chronic Lymphocytic Leukemia

The treatment paradigm of chronic lymphocytic leukemia continues to advance, with many ongoing clinical trials investigating combinations seeking to build upon the success seen with Bruton’s tyrosine kinase inhibitors. Such potential combination therapies for CLL include venetoclax (Venclexta) with either ibrutinib (Imbruvica) or acalabrutinib (Calquence).

According to findings from the phase III MURANO trial recently published in the<em> New England Journal of Medicine, </em>the venetoclax&nbsp;(Venclexta) plus rituximab&nbsp;(Rituxan) regimen lowered the risk of disease progression or death by 83% in comparison with bendamustine (Treanda) plus rituximab&nbsp;(Rituxan) in patients with relapsed or refractory chronic lymphocytic leukemia<em>.</em>

Constantine S. Tam, MD, associate professor, Peter MacCallum Cancer Centre, discusses the phase III DUO trial, a randomized comparison of duvelisib versus ofatumumab (Arzerra) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia.

According to phase I findings published in <em>The Lancet Oncology,</em>&nbsp;an&nbsp;objective response rate of 37% was induced in patients with&nbsp;relapsed/refractory lymphoma or chronic lymphocytic leukemia treated with the&nbsp;PI3K-delta inhibitor umbralisib.

The clinical course of chronic lymphocytic leukemia is highly variable, and a subset of patients may never need clinical intervention. However, most patients will eventually require treatment during their disease.

Susan O&rsquo;Brien, MD,&nbsp; discusses the tremendous impact that has been seen with ibrutinib following the long-term follow-up of the RESONATE studies and highlights where this regimen is headed in the future of treatment for patients with CLL.

Based on improved insight into chronic lymphocytic leukemia biology and pathophysiology, approaches to identify patients who are at higher risk for disease progression have been refined, as have strategies to select therapies that maximize treatment outcomes due to their selectivity for distinctive phenotypic or physiological features of the respective CLL cells.

Matthew S. Davids, MD,&nbsp;sheds light on the significant findings of this study and gave a look ahead to ibrutinib combination therapies in the future treatment landscape of CLL.

Prospects for patients with chronic lymphocytic leukemia have improved with the use of targeted agents such as ibrutinib; however, complete remissions are rare, and treatment options for patients relapsing after treatment with ibrutinib remain limited.

Recent years have seen major advances in diagnostic approaches in CLL, and disease assessment may now include analysis of multiple genetic mutations in addition to recurrent cytogenetic changes. Furthermore, with the development of novel treatment approaches, the significance of prognostic markers is shifting.

Based on supporting data from the phase III DUO trial and the phase II DYNAMO study, duvelisib has been submitted to the FDA for a full approval&nbsp;for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and an accelerated approval for the treatment of patients with relapsed/refractory follicular lymphoma.

Matthew S. Davids, MD, Associate Director, Dana-Farber Cancer Institute Center for Chronic Lymphocytic Leukemia, discusses a multicenter study of ibrutinib (Imbruvica) plus FCR as a frontline therapy for younger patients with chronic lymphocytic leukemia (CLL).&nbsp;<br /> &nbsp;

Matthew S. Davids, MD, MMSc, recently discussed the treatment choices for patients with chronic lymphocytic leukemia, and the factors he considers when choosing a treatment, based on 2 patient cases.

Arsenic trioxide (Trisenox) has been approved by the FDA in&nbsp;combination with the all-trans retinoic acid agent tretinoin for the treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia with the t(15;17) translocation or <em>PML-RARA</em> gene expression.

The Therapeutic Approach for High-Risk CLL