First‐line R‐CVP versus R‐CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4

Abstract

Summary R‐CVP (cyclophosphamide, vincristine, prednisone) and R‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non‐Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression‐free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R‐CVP to R‐CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa‐associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R‐CVP or R‐CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m2 q 2 months for 12 cycles. Primary endpoint was event‐free survival (EFS). Two‐hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R‐CHOP: 127, R‐CVP: 123). Median age was 56 years (21–85), 44% were male, 90% were in stage III–IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R‐CHOP and R‐CVP groups (P = 0·218) respectively. After a median follow‐up of 67, 66, and 70 months, five‐year EFS was 61% vs. 56% (not significant), progression‐free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R‐CHOP vs. the R‐CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients., in the R‐CHOP and the R‐CVP groups respectively. This multicentre randomized study with >five‐year follow‐up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R‐CVP or R‐CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R‐CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second‐line therapy.

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study

“…9 The ORR by 2007 IWG criteria in the present study (CT-P10, 93%; rituximab, 94%) was also similar to the ORR of 97% (assessed by CT scans per IWG criteria) reported in a study evaluating rituximab and CVP (R-CVP) induction treatment followed by maintenance rituximab in patients with previously untreated indolent non-Hodgkin lymphoma. 12 Assessment methods and treatment regimens vary between studies, but findings for time-to-event analyses in our study were generally comparable with previous reports in patients with advanced-stage FL who had been treated with induction R-CVP followed by maintenance rituximab. The estimated 3-year PFS rates were 77% in 2 previous studies, 13,14 compared with 67% (CT-P10) and 69% (rituximab) in ours.…”

Population-based epidemiological data of follicular lymphoma in Poland: 15 years of observation

“…Our study was conducted in the rituximab era. In 1997 this monoclonal anti-CD20 antibody gained the Food and Drug Administration approval in FL treatment, and in early 2000 the European Union and Poland have started its implementation 32,33 . The standardized death rate in Poland in 2014 is similar to the SEER data 34 .…”

Large-Scale Proteomic Analysis of Follicular Lymphoma Reveals Extensive Remodeling of Cell Adhesion Pathway and Identifies Hub Proteins Related to the Lymphomagenesis

“…The HT rate of FL is difficult to estimate [ 11 ] and it is assumed about 2–3% per year from diagnosis [ 12 , 13 , 14 ]. Recently, significantly prolonged progression-free survival was observed when treated with modern therapies [ 15 , 16 ], however its remains incurable for the majority of elderly individuals [ 6 , 17 , 18 ]. Therefore, extensive “omics” studies dealing with the molecular aspect of FL are highly recommended.…”