Lenalidomide is an oral immunomodulatory agent approved in relapsed multiple myeloma with dexamethasone, for transfusion-dependent anemia in myelodysplastic syndrome associated with deletion 5q, and in relapsed/progressive mantle cell lymphoma following bortezomib. In recent clinical trials, lenalidomide has shown promising activity in hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Starting doses and dosing schedules vary by malignancy, with lenalidomide started at a lower dose for CLL than for NHL or multiple myeloma. Certain adverse events (AEs) are common across tumor types (e.g., neutropenia, thrombocytopenia, fatigue), whereas others are more often associated with CLL patients (e.g., tumor lysis syndrome and tumor flare reaction). Effective management requires awareness of these differences as well as appropriate prophylaxis, monitoring, and treatment of AEs. This article reviews the efficacy and safety of lenalidomide in CLL and NHL, focusing on approaches for the advanced practitioner to improve patient quality of life through optimal management of side effects. With these steps, lenalidomide can be administered safely, at the best starting doses and with minimal dose interruptions or reductions across hematologic malignancies.
Richter transformation (RT) is the development of high-grade lymphoma in patients with B-cell chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). CLL/SLL is a heterogenous disease with a highly variable clinical course. Disease progression in patients with CLL continues to occur even in the era of novel therapies. A small percentage of CLL patients will develop aggressive histologic transformation to diffuse large B-cell lymphoma (DLBCL), commonly known as RT. It is known that certain genetic aberrations predispose patients to RT, including mutations in NOTCH1, TP53, CDKN2A, and unmutated IGHV somatic mutations. Historically, challenges existed in making a definitive diagnosis of RT. More recently, clonal relationships between the underlying CLL and DLBCL-RT are primarily diagnosed by sequencing immunoglobulin genes. Yet, RT continues to present challenges to health-care providers in managing patients with CLL/SLL, even with novel agents. This article aims to increase advanced practitioner awareness of predictive factors for RT, clinical manifestations, and diagnostic criteria to promote early recognition and intervention. Advanced practitioners need to be cognizant of clinical signs of RT and of diagnostic criteria for an appropriate and rapid diagnosis. In doing so, the advanced practitioner can promote early diagnosis and intervention, which may improve patient outcomes, given the dismal prognosis of RT.
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