LOW-DOSE FCR IN THE TREATMENT OF ELDERLY/COMORBID PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL): UPDATED RESULTS OF PROJECT Q-LITE BY CZECH CLL STUDY GROUP

Sborník

Background. 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 approach because of advanced age and/or serious comorbid conditions leading to unacceptable toxicity. For these patients, chlorambucil remains so far the standard of treatment. However, regimens based on low-dose fludarabine have recently demonstrated promising results in small studies. Aims. to assess efficacy and safety of low-dose FCR regimen used in elderly/comorbid patients with CLL/SLL: updated results are presented. Patients and Methods. Between March 2009 and February 2012, we treated 169 pts with active disease and efficacy/safety data are currently available on 145 pts (CLL, n=137, SLL, n=8, males, 59%, median age, 69 years [range, 58 - 87], median Cumulative Illness Rating Score 4.5 [range, 0-14], median creatinine clearance, 67 ml/min) by low-dose FCR at 17 centers cooperating within Czech CLL Study Group. Dose reduction of chemotherapy in comparison to regular FCR regimen was following: 50% of fludarabine dose (12 mg/m² i.v. or 20 mg/m² orally on day 1-3) and 60% of cyclophosphamide dose (150 mg/m² i.v./p.o. on day 1-3). Rituximab was administered in standard schedule (375mg/m² i.v. day 1 in 1st cycle, 500mg/m² i.v. day 1 from 2^nd cycle). Treatment was repeated every 4 weeks. Antimicrobial prophylaxis with sulfamethoxazol/ trimethoprim and aciclovir or equivalents was recommended. A total of 50% pts were untreated, remaining half had relapsed/refractory disease (median previous lines 1, range, 1-6). Advanced Rai stages (III/IV) were present in 61% pts; 39% had bulky disease. IgVH genes were unmutated in 74%; according to Doehner´s FISH hierarchical model, del 11q was present in 34% and del 17p in 6%. Results. Based on intention-to-treat principle, the overall response/complete response rate (including clinical CR [without bone marrow biopsy] and CR with incomplete blood count recovery) was 81/43% in first line and 69/35% in relapse. Serious (CTCAE grade III/IV) neutropenia occurred in 53%, thrombocytopenia in 12% and anemia in 12% of pts. Serious infections developed in 10% of pts. Median follow-up of living patients was 13 months (range, 2-31). Twenty-five patients have died; the most common causes of death were CLL progression and infections. Longer follow-up is necessary for PFS/OS and quality of life data. Conclusions. Treatment of elderly/comorbid CLL/SLL patients with low-dose FCR demonstrated promising results in first line as well as relapsed/refractory setting. Toxicity was acceptable and manageable. Recruitment in the study is ongoing and updated results will be presented. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic

Haematologica, 2012; 97(s1):  59