ORLANDO, Fla.—Patients with follicular lymphoma who receive initial treatment with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) followed by 2 years of maintenance with rituximab had outcomes that compared favorably with more intensive combinations, results of a retrospective population-based analysis using the British Columbia (BC) Cancer Agency Lymphoid Cancer Database has found.
Patients with FL refractory to R-CVP have a “dire” prognosis, necessitating improved therapeutic approaches for this high-risk subgroup, noted Alden A. Moccia, of the BC Cancer Agency, Vancouver, BC, Canada, and colleagues. The recently reported PRIMA trial was the first to evaluate the benefit of rituximab maintenance following first-line immunochemotherapy in this patient population. In that trial, the majority of patients received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) induction followed by rituximab maintenance administered bimonthly for 2 years. Results yielded a substantial benefit in progression-free survival (PFS), Dr. Moccia noted in a poster presentation during the 52nd American Society of Hematology Annual Meeting and Exposition.
In the current analysis, the investigators assessed outcomes in an unselected population of chemotherapy-naïve patients with FL treated in BC with R-CVP followed by observation or 2 years of maintenance with rituximab. Since 2004, standard treatment policy in BC has recommended 8 cycles of R-CVP as first-line systemic therapy for symptomatic advanced-stage FL. Since 2006, maintenance with rituximab 375 mg/m2 IV every 3 months for 2 years has been recommended for patients achieving a complete (CR/CRu) or partial (PR) remission following induction therapy. Asymptomatic patients generally undergo a period of watchful waiting, with systemic therapy initiated only when clinically indicated, Dr. Moccia reported.
All patients with FL who received first-line R-CVP between March 2004 and January 2010 were included in the analysis. Outcomes of patients who received rituximab maintenance were compared with those of patients who responded to R-CVP but did not receive maintenance (ie, prior to the routine maintenance policy). Primary end point was PFS, defined as the interval from the beginning of R-CVP to first progression, relapse, or death from any cause. Patients who progressed while on R-CVP or did not achieve at least a PR were considered to have refractory lymphoma.
Median age of the 251 patients identified in the analysis was 60 years (range, 31-86 years), and 58% were male. Eighty-three percent had stage 3/4 disease; 30%, bulky disease ≥10 cm; 20%, B symptoms; and 16% had elevated LDH. Follicular Lymphoma International Prognostic Index (FLIPI) variables were retrievable on 95% of patients; 26% were low risk; 29%, intermediate risk; and 45%, high risk. FL grade 1 was observed in 56% of patients; 29%, grade 2; 14%, grade 3; and 1%, not otherwise specified.
Prior to initiation of systemic treatment, 48 patients (19%) were on observation, with a median time between diagnosis and first cycle of R-CVP of 19 months (range, 4-130 months). At a median follow-up of 36 months (range, 0-74 months), 33 patients (13%) had died (24 from lymphoma, 3 from treatment toxicity, and 6 from unrelated causes while in sustained remission).
Twenty-seven patients (11%) had lymphoma refractory to R-CVP and an additional 8 (3%) failed to complete therapy (3 due to poor tolerance, 3 died from treatment toxicity, and 2 died from unrelated causes). Patients with refractory disease were treated as follows: 6 purine analogue-based regimens, 13 R-CHOP, 3 radiation therapy, 3 palliative care, and 2 other chemotherapy regimens. Patients with refractory disease had extremely poor outcomes; 3-year overall survival (OS) was 48%.
Of the 251 patients, 216 responded to R-CVP (ORR 86%: CR/CRu 44%; PR 37%; 5% detailed radiologic response not available). Following response to R-CVP, 59 patients were observed and 167 received rituximab maintenance. These 2 groups had similar baseline characteristics in terms of age, stage, gender, and FLIPI score; however, median follow-up was longer for observation patients (59 months) compared with those receiving rituximab maintenance (34 months).
Eighteen patients (11%) developed progressive disease while receiving rituximab maintenance. Within the subset of patients with available imaging studies for review, 23% in PR after R-CVP converted to CR/CRu while on rituximab maintenance. The 3-year PFS was significantly improved for patients receiving rituximab maintenance (83%) vs those on observation alone following response to R-CVP (62%; P=0.002) (see Figure). Please click here for more study data. The 3-year OS was similar in the 2 cohorts (93% vs 93%, P=0.985).