ASCO 2016 Abstract #7505: Maintenance Therapy with Rituximab After FCR Induction Contributes to Longer Median PFS When Treating Older Patients with CLL
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 elderly 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 event-free survival, overall survival, and overall response rate. Estimated enrolment of this trial was approximately 500 patients, and the inclusion criteria included B-CLL, Matutes score 4 or 5, Binet score B or C, and age >65 years.
A longer median PFS was achieved in the RTX arm than the OBS arm (58.3 months vs 49.0 months) which translates into three-year PFS rates of 83.0% in the RTX arm and 64.2% in the OBS arm. The authors concluded that RTX maintenance after FCR induction does add benefit, but is associated with a higher risk of toxicity.
Background: A promising concept to improve outcome in CLL is maintenance with immunotherapy after induction with FCR to improve quality and duration of response.
Methods: Treatment-naive, ≥ 65 y, fit pts with B-CLL and no del17p, received an induction with 4 cycles of FCR, a shortened schedule chosen to reduce the risk of cumulative toxicity in elderly pts with physiological decline. Pts in CR/PR were randomly allocated to maintenance 500 mg/m2rituximab (RTX arm) q2m x 2 y or observation (OBS arm). Primary objective was to demonstrate an improvement in 3-y PFS from randomization from 50% in OBS arm to 66% in RTX arm. 406 patients were required. At randomization, pts were stratified for IGHV status, del11q and response. Median FU from randomization is 43.6 m.
Results: 409 pts were randomized (202 in RTX arm; 207 in OBS arm). Median age was 71.3 y, 66.3% were males, 25.7/11.0% were in CR/CRi and 62.8% in PR post-FCR, 21.3% had del11q and 54.8% unmutated IGHV. Median PFS in RTX arm was 59.3 m (95% CI: 49.6; not reached) as compared to 49.0 m (95% CI: 40.9; 60.5) in OBS arm (HR 0.597, 95% CI: 0.437; 0.814, P.0011), corresponding to a 3-y PFS of 83.0% and 64.2% in each arm, respectively. Estimated 3-y OS was 92.6% and 87.2% in RTX and OBS arm, respectively (NS). Rituximab maintenance significantly improved PFS in pts with or without del11q and in those with unmutated IGHV. SAEs for hematological toxicity were declared in 6.9% and 1.9% (P.027), and SAEs for infectious toxicity in 18.8% and 10.1% (P.036) of the pts, in RTX and OBS arms, respectively. Sixty-nine deaths occurred post-randomization, 32 in RTX arm and 37 in OBS arm. Secondary cancer (excluding BCC) occurred in 15.3% (incl. 5 MDS) and 11.1% (incl. 3 MDS) of pts in RTX and OBS arm, respectively.
Conclusions: Two-y maintenance rituximab significantly improved PFS as compared to observation in selected elderly CLL pts in response after FCR induction. This benefit was also observed in pts with unfavorable characteristics. Maintenance was feasible but associated with a higher incidence of toxic events. Benefit from maintenance will be further analyzed according to MRD eradication. Clinical trial information: NCT00645606.
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).