Low-Dose Fludarabine and Cyclophosphamide Combined with Rituximab In the Treatment of Elderly/Comorbid Patients with chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Preliminary Results of Project Q-Lite by Czech CLL Study Group

Combination of fludarabine, cyclophosphamide and rituximab (FCR) is currently considered the treatment of choice in physically fit patients (pts) with chronic lymphocytic leukemia (CLL). However, many patients cannot tolerate this aggresive treatment because of advanced age and/or serious comorbid conditions. For these patients, chlorambucil has remained so far the standard of treatment. Low-dose fludarabine-based regimens have recently demonstrated promising results in small studies.

to assess efficacy and safety of low-dose FC or FCR regimen used in elderly/comorbid patients with CLL.

Between March 2009 and June 2010, we treated 74 pts with active disease (CLL, n=70, SLL, n=4, 57% males, median age, 70 years [range, 58–83], median Cumulative Illness Rating Score 4 [range, 0–10]) by low-dose FC/FCR at fourteen centers cooperating within Czech CLL Study Group. Dose reduction of chemotherapy was as follows: fludarabine to 50% (12 mg/m² i.v. or 20 mg/m² orally on Days 1–3), cyclophosphamide to 60% (150mg/m² i.v./p.o. D1-3). The dose of rituximab was standard (375mg/m² in 1st cycle, 500mg/m² from 2nd cycle). The choice of regimen (FC vs FCR) was at the discretion of the attending physician. Treatment was repeated every 4 weeks. Antimicrobial prophylaxis with cotrimoxazole and aciclovir or equivalents was recommended. Fifty per cent of pts were treated in first line, the remaining half had relapsed/refractory CLL. Rai stage III/IV was present in 57% pts; 39% had bulky disease. IgVH genes were unmutated in 74%; according to hierarchical model, del 11q was present in 32% and del 17p in 8%.

FCR was used in 72 pts, FC in 2. Based on intention-to-treat principle, the overall response/complete response rate (including clinical CR and CR with incomplete blood count recovery) was 70/35%; 34 pts are still on treatment. No data on PFS/OS are available yet. Serious (CTC grade III/IV) neutropenia occurred in 51%, thrombocytopenia in 13% and anemia in 10% of pts. Serious infections were diagnosed in 13% of pts. Three pts (4%) died, all of them after failure of treatment (pneumonia, n=2, pulmonary embolism, n=1).

Treatment of elderly/comorbid CLL patients with low-dose FC/FCR demonstrated very promising results. Toxicity was acceptable and manageable. Longer follow-up is needed for the assessment of PFS and OS. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic.

Smolej: Roche: Honoraria; Bayer-Schering: Honoraria; Genzyme: Honoraria. Off Label Use: Low-dose FCR in elderly/comorbid patients with CLL. Belada: Roche: Consultancy, Honoraria. Motyckova: Roche: Honoraria.