This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.
The CLL 2007 SA trial is a randomized, phase III study conducted by the French FILO group and compares rituximab (RTX) maintenance versus observation (OBS) after induction with fludarabine, cyclophosphamide, and rituximab (FCR) for treating newly diagnosed, fit, elderly (≥65 years) patients with previously untreated Chronic Lymphocytic Leukemia (CLL).
The primary outcome measure for this study was three-year Progression Free Survival (PFS) supplemented by secondary outcome measures which included EFS, OS, and ORR. Inclusion criteria included B-CLL, Matutes score 4 or 5, Binet score B or C, and age ≥65 years, and no del(17p).
Patients were administerd 4 cycles of induction FCR and then 409 patients in CR/PR were randomized to either maintenance rituximab 500mg/m2 q2m for 2 years (n=202), or observation (n=207). At randomization, patients were stratified for IGHV status, del(11q), and response.
- Median age = 71.3 years; males = 66.3%
- At randomization, pts in CR/CRi = 25.7%/11.0%; PR = 62.8%
- Del(11q) = 21.3%; unmutated IGHV = 54.8%
- Median follow-up from randomization = 43.6 months
- Median PFS: RTX arm = 59.3 months (95% CI, 49.6–not reached); OBS arm = 49.0 months (95% CI, 40.9–60.5; HR, 0.597; 95% CI, 0.437–0.814; P = 0.0011)
- 3-year PFS: RTX arm = 83.0%; OBS arm = 64.2%
- Estimated 3-year OS: RTX arm = 92.6%; OBS arm = 87.2%
- Rituximab maintenance significantly improved PFS in pts with or without del(11q) and in those with unmutated IGHV
- Hematological SAEs were reported in 6.9% of RTX pts and 1.9% of OBS pts (P = 0.027)
- Infectious SAEs were reported in 18.8% of RTX pts and 10.1% of OBS pts (P = 0.036)
- Post-randomization, 69 deaths were reported (RTX n=32; OBS n=37)
- Secondary cancers, excluding Basal Cell Carcinoma, were reported in 15.3% (including 5 MDS) RTX pts and 11.1% (including 3 MDS) OBS pts
In elderly patients with CLL who achieved a response to induction with FCR, PFS was significantly improved with 2 years of maintenance rituximab compared to observation. This benefit was also observed regardless of MRD status, and in patients with unfavorable characteristics such as del(11q) and unmutated IGHV. Moreover, no difference in OS was found between observation and maintenance rituximab. However, a higher incidence of adverse events was found with rituximab maintenance compared to observation, in particular hematologic and infectious events. Caroline Dartigeas concluded the talk by advising that patients should be carefully followed to detect secondary cancers as early as possible and elderly patients should be monitored for long-term toxicities.
1. Dartigeas C, et al. Rituximab maintenance after induction with abbreviated FCR in previously untreated elderly (≤ 65 years) CLL patients: results of the randomized CLL 2007 SA trial from the French FILO Group (NCT00645606). J Clin Oncol 34, 2016 (suppl; abstr 7505).