Low‐dose fludarabine and cyclophosphamide combined with rituximab in the first‐line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long‐term results of project Q‐lite by the Czech CLL Study Group

Summary Therapeutic options used to be very limited for treatment‐naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo‐immunotherapy. Because dose‐reduced fludarabine‐based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low‐dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full‐dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy‐chain variable‐region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m2 intravenously (iv) or 20 mg/m2 orally on days 1–3 and cyclophosphamide to 150 mg/m2 iv/orally on days 1–3. Grade 3–4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression‐free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low‐dose FCR is a well‐tolerated and effective first‐line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726).