OVERVIEW OF CLL

Chronic lymphocytic leukemia is a neoplastic disease of clonal CD5 + B-cells that is characterized clinically by lymphocytosis, cytopenias, and infection.^1-3 This disease primarily affects older adults with a median age of diagnosis of patients in their seventies.⁴ In 2016, an estimated 18 960 new cases will be diagnosed in the United States with an expected 4660 deaths yielding a predicted 5-year survival of 82.6%.⁴

Newly diagnosed patients with early stage disease are generally monitored without treatment until they show signs of disease progression; however, undergoing treatment early in their disease state does not necessarily prolong survival.¹ Historically, treatment was limited to combination therapy with alkylator-based treatment (chlorambucil), with corticosteroids (prednisone), until the introduction of the nucleoside analogue fludarabine in the early 1990s. The US Food and Drug Administration (FDA) approved rituximab for treating patients with follicular non-Hodgkin's lymphoma in 1997, which opened the way for new combination therapies for patients with CLL. In 2010, rituximab with fludarabine and cyclophosphamide was approved for previously treated and treatment-naive patients with CLL.^5-6 Today, regimens incorporating alkylating agents, nucleoside analogues, and anti-CD20 monoclonal antibodies (cyclophosphamide, fludarabine, and rituximab) give markedly improved remission duration as compared to older treatments. However, regimens incorporating alkylating agents, nucleoside analogues, and anti-CD20 monoclonal antibodies are also associated with a higher rate of reported toxicities compared to chlorambucil and prednisone, which preclude their use in patients with medical comorbidities.^7-8

Biomarkers Associated with Poor Prognosis

Cytogenetic abnormalities are present in approximately 80% of patients with CLL. The most commonly defined cytogenetic abnormalities include deletions at 6q, 11q, 13q and 17p or chromosomal additions such as trisomy 12.⁴ Specific deletions such as del(11q) and del(17p) are predictive of significantly worse outcomes in patients with CLL with a shorter progression-free survival (PFS) and overall survival (OS) (Table 1).^9-11