Front-Line Therapy with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) Followed by 2 Years of Rituximab Maintenance for Follicular Lymphoma (FL) Is Associated with Excellent Outcomes and Improved Progression-Free Survival (PFS) In Comparison to No Maintenance
Authors: Moccia Alden A. , Hoskins Paul , Klasa Richard , Savage Kerry J. , Shenkier Tamara , Slack Graham W. , Gascoyne Randy D. , Connors Joseph M. , Sehn Laurie H. 
Published: October 2019

Abstract
Abstract 1803

Introduction:
The recently reported PRIMA trial was the first to evaluate the benefit of rituximab maintenance (R-maintenance) following first-line immunochemotherapy in FL (Salles G, ASCO 2010). In that trial, the majority of patients (pts) received R-CHOP induction and R-maintenance was administered bi-monthly for 2 years, yielding a substantial benefit in PFS. We assessed outcomes in an unselected population of chemotherapy-naïve pts with FL treated in British Columbia (BC) with R-CVP followed by observation or 2 years of R-maintenance.

Patients and Methods:
Since 2004, the standard treatment policy in BC has recommended 8 cycles of R-CVP as first-line systemic therapy for symptomatic advanced stage FL. Since 2006, R-maintenance (rituximab 375 mg/m2 IV every 3 months for 2 years) has been recommended for pts achieving a complete (CR/CRu) or partial (PR) remission following induction therapy. Asymptomatic pts generally undergo a period of watchful waiting, with systemic therapy initiated only when clinically indicated. We performed a retrospective population-based analysis using the BC Cancer Agency Lymphoid Cancer Database and included all pts with FL who received first-line R-CVP between March 2004 and January 2010. Outcome of pts who received R-maintenance was compared to the group of pts who responded to R-CVP but did not receive maintenance (i.e. prior to routine maintenance policy). Primary endpoint was PFS, defined as the interval from the beginning of R-CVP to first progression, relapse or death from any cause. Pts who progressed while on R-CVP or did not achieve at least a PR were considered to have refractory lymphoma.

Results:
251 pts were identified. Clinical characteristics at diagnosis were: median age 60 y (range 31–86 y), 58% male, 83% stage III/IV, 30% bulky disease ≥10cm, 20% B symptoms, 16% elevated LDH. FLIPI variables were retrievable on 95% pts: 27% low-risk, 29% intermediate-risk, 45% high-risk. Histology: 56% FL grade 1, 29% FL grade 2, 14% FL grade 3, 1% FL NOS. 48 pts (19%) were on observation before systemic treatment was initiated with a median time between diagnosis and first cycle of R-CVP of 19 m (range 4–130 m). At a median f/u of 36 m (range 0–74 m), 33 pts (13%) have died (24 from lymphoma, 3 from treatment toxicity, 6 from unrelated causes while in sustained remission). 27 pts (11%) had lymphoma refractory to R-CVP and an additional 8 pts (3%) failed to complete therapy (3 due to poor tolerance, 3 died from treatment toxicity, 2 died from unrelated causes). Pts with refractory disease were treated as follows: 6 purine analog-based regimens, 13 R-CHOP, 3 radiation therapy, 3 palliative care and 2 other chemotherapy regimens. Outcome of refractory pts was extremely poor, with a 3-year OS of 48%. 216/251 pts responded to R-CVP (ORR 86%: CR/CRu 44%, PR 37%, 5% detailed radiologic response not available). Following response to R-CVP, 59 pts were observed and 167 pts received R-maintenance. These 2 groups had similar baseline characteristics in terms of age, stage, gender and FLIPI score; however, median f/u was longer for observation pts compared to R-maintenance pts, 59m vs 34m. Eighteen pts (11%) developed progressive disease while receiving R-maintenance and within the subset of pts with available imaging studies for review, 23% pts in PR after R-CVP converted to CR/CRu while on R-maintenance. The 3-y PFS was significantly improved for pts receiving R-maintenance compared to pts on observation alone after having responded to R-CVP, 83% vs 62%, p=0.002 (see figure). The 3-y OS was similar in the 2 cohorts (93% vs. 93%, p=0.985).

Conclusions:
This population-based analysis confirms the benefit of R-maintenance following immunochemotherapy in pts with untreated FL. R-CVP followed by 2 years of R-maintenance is a well-tolerated and effective therapy with outcomes that compare favorably with more intensive combinations. Patients with lymphoma refractory to R-CVP have a dire prognosis; improved therapeutic approaches are needed for this high-risk subgroup.

Disclosures:
Connors: Hoffmann-La Roche: Research Funding. Sehn:Hoffmann-La Roche: Consultancy, Research Funding; Genentech: Consultancy.