Health Related Quality of Life (HRQOL) in Patients Receiving Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) or Fludarabine and Cyclophosphamide (FC) for First Line Therapy with Advanced Chronic Lymphocytic Leukemia (CLL).

Chemoimmunotherapies like the FCR combination have been shown to increase complete remission rates and progression-free survival in patients with CLL in comparison to chemotherapies without biologicals (Hallek et al., ASH 2008). Until now little is known on HRQOL outcome of CLL patients receiving chemoimmunotherapy. Therefore we assessed the HRQOL in patients with advanced CLL, who were randomized between FC and FCR treatment within an international randomized trial of the German CLL Study Group (GCLLSG).

817 pts with good physical fitness as defined by a cumulative illness rating scale (CIRS) score of up to 6 and a creatinine clearance (cr cl) ≥ 70 ml/min were enrolled between July 2003 and March 2006. Pts were randomly assigned to receive 6 courses of either FC (N=409; F 25mg/m² i.v. d1–3 and C 250 mg/m² i.v. d1–3; q 28 days) or FC plus R (N=408; 375 mg/m² i.v. d 0 at first cycle and 500 mg/m² d1 all subsequent cycles; q 28 days). The EORTC C30 questionnaires were sent to all patients included in Germany or Austria at baseline, after 3, 6, 12 months (mo) and then in yearly follow-up (FU). In all other countries questionnaires were handed out to the patients personally on the same time points during their visits in the study center. The analysis of the questionnaires was performed according to the EORTC recommendations (Aaronson et al., 1993). The questionnaire contained a global health scale, five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain, nausea and vomiting) as well as six single items (dyspnea, appetite loss, sleep disturbances, financial impact, constipation and diarrhea). Mean score values of the EORTC scales ranged between 0 and 100. High scores in the functional scales represent good HRQOL, low scores in the symptom scales a low symptom burden.

HRQOL was evaluated in 763 (93%) of the included patients who completed at least one questionnaire (376 (49%) FC and 387 (51%) FCR treated patients). The compliance rate was significantly higher in those countries, where the questionnaire was handed out personally (96% in other countries versus 92% in Germany and Austria; P=0.013). Pts answering the baseline questionnaire and at least one further questionnaire (444; 58%) were compared to those how did not (319, 42%): pts with only one or a missing baseline questionnaire had a significantly higher CIRS score (1,7 vs 1,4; P=0.007) and more frequently leukocytopenias (24% CTC grade 3 and 4 leukocytopenias vs 13%; P< 0.001). Age, distribution of Binet stages, gender, poor prognostic factors (del(11q) or del(17p), unmutated IgVH) and treatment arms were similar distributed between both groups. There were also no differences in the rate of other toxicities or response rates. A total of 482 questionnaires were available initially, 406 at interim staging, 454 at final staging, 496 after 12 mo FU, 414 after 24 mo FU and 198 after 36 mo FU.

A comparison of the two treatment arms at interim or final staging after 3 and 6 months respectively showed no significant difference between both arms with regards to the global health status, functional scales and symptom scales. Dyspnoe was scored significantly higher during FC treatment in comparison to FCR (23 versus 18; P = 0.023). At 12, 24 and 36 months of FU no significant difference between FC and FCR in all functional scales, symptom scales, single item and global health status was found. Both treatment arms showed slight improvement (defined as difference of 5-10 points) of global health status at 12 months FU in comparison to baseline (FC: 62 at baseline vs 68 at FU 12; FCR: 62 vs 70).

Although the FCR regimen is associated with a higher rate of cytopenias in patients' perception this increased hematological toxicity does not result in a difference in HRQOL between both treatment arms. After a median observation time of 38 mo the better efficacy of the FCR regimen with regards on response rates and progression-free survival does not yet result in an improved HRQOL. For the final evaluation of HRQOL outcome after chemoimmunotherapy a longer is FU is needed.

Eichhorst:Roche: Honoraria, Research Funding; Mundipharma: Research Funding; Hospira: Honoraria. Fischer:Roche: Travel Grand; Munipharma: Travel Grand. Fink:Roche: Travel Grand. Fingerle-Rowson:OrthoBiotech: Employment; Roche: Honoraria. Westermann:Roche: Travel Grand. Wendtner:Roche: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; BayerSchering: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Hallek:Roche: Research Funding, Speakers Bureau; Mundipharma: Research Funding, Speakers Bureau.