A 61-year-old man with a history of chronic lymphocytic leukemia (CLL) presents with complaints of worsening fatigue and night sweats. He was diagnosed with CLL 3 years ago on routine blood count testing. He has no major medical comorbidities. On examination, he has several 2-to 3-cm lymph nodes in the cervical and axillary area. Spleen is palpable 5 cm below the costal margin. Blood counts show lymphocytosis with thrombocytopenia and anemia. Prognostic markers include deletion 13q by fluorescence in situ hybridization analysis and mutated IGHV. You are asked by the hematology fellow you are supervising about the best treatment of this patient.
Learning Objectives• To understand the role of chemoimmunotherapy in the management of young patients with CLL • To understand the role of novel targeted therapies in this patient population • To recognize the emerging role of IGHV mutation status in treatment selection for these patients Therapy options for patients with chronic lymphocytic leukemia (CLL) have undergone a remarkable evolution in the last several years. 1 Though chemoimmunotherapy (CIT) has been the standard first-line option for young fit patients with CLL, the overall role of CIT in the management of patients with CLL is diminishing with an increasing role for targeted therapies. Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has shown remarkable clinical activity in patients with CLL, and is currently approved for patients with CLL, both for previously untreated, and for patients with relapsed disease. Idelalisib, a phosphatidylinositol 3-kinase (P13K) kinase inhibitor, is approved in combination with rituximab for patients with relapsed CLL. Venetoclax, a BCL-2 inhibitor, was recently approved for patients with relapsed CLL with deletion 17p. Several other agents are in clinical development and will likely further enhance the therapeutic armamentarium. Early trials with these targeted therapies were conducted in relapsed/refractory patients; these drugs are now being explored in the first-line setting in several trials, including in "young fit" patients (the patient in the scenario in the Abstract).The definition of "young fit" (ie, those eligible for intensive CIT) varies.2 In the United States, age is most commonly used to identify patients eligible for intensive CIT, with patients younger than 65 years of age typically offered CIT as first-line therapy. The German CLL Study Group (GCLLSG) has used comorbidity index (Cumulative Illness Rating Scale [CIRS]) and renal function to identify CIT-eligible patients (CIRS #6 and creatinine clearance $70 mL per minute).3 CIT has been the standard therapy for this group of patients; however, ibrutinib is currently approved for all patients with CLL, including young fit patients with CLL who would otherwise be eligible for CIT. This poses a question about the appropriate therapy for this group of patients.
ChemoimmunotherapyCIT, such as with fludarabine, cyclophosphamide (FC), rituximab (FCR), has been the standard therapy for CLL (Table 1). In a singlec...