RCHOP-21 Vs. RCHOP-14 for the Treatment of Newly Diagnosed Diffuse Large B Cell Lymphoma: A Prospective Randomized Phase III Clinical Trial from Cswog

Background:CD20-antibody (rituximab) plus CHOP chemotherapy (R-CHOP) have become the first-line regimen for CD20 positive DLBCL since the introduction of rituximab at the end of 1990s. Our group (Chinese south-west oncology group, CSWOG) planned to evaluate the efficacy and toxicity of biweekly schedule of RCHOP (RCHOP-14) compared to triweekly RCHOP (RCHOP-21) for DLBCL.

Purpose:RCHOP-14 vs. RCHOP-21 for untreated diffuse large B-cell lymphoma (DLBCL), compare the 5-year disease-free survival (DFS), overall survival (OS), response rate and the side effects.

Patients and methods:Patients older than 18 years, newly diagnosed of CD20-positive DLBCL with adequate organ function were recruited. All patients were randomized into two groups after provided written informed consent, and received RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. The RCHOP-14 group was administered every 2 weeks, patients received prophylactic granulocyte colony-stimulating after each chemotherapy cycle. The control group RCHOP-21 was administered every 3 weeks. The planned cycles of chemotherapy was 6 to 8 cycles. Patients received imaging evaluation at the baseline and every 2 cycles of chemotherapy. Radiotherapy was recommended to treat local residue or bulky tumor. Vital signs, physical examination, and laboratory studies were documented at each follow-up visit.

Results:  From January 2008 to December 2014, a total of 702 patients with newly diagnosed DLBCL were recruited in 14 cancer centers of CSWOG. There were 407 males (58.0%) , 295 females (42.0%) , and median age of 52 years (range 18-80 years). 353 assigned to the RCHOP-21 group and 349 assigned to the RCHOP-14 group, patients in the two groups totally received 3989 cycles of chemotherapy, an average of 5.70 cycles per patient. There was no significant difference between the RCHOP-21 and RCHOP-14 groups in terms of sex, age, Ann Arbor stage, International Prognostic Index, B symptoms, extranodal involvement and seropositive status for hepatitis-B surface antigen. Overall, 496 (70.7%) achieved CR, 136 (19.4%) PR, 16 (2.3%) SD and 50 (7.1%) PD. For RCHOP-21 group, the incidence of CR, PR and PD was 72.8%, 18.4%, 6.5%, respectively, the response rate was 91.2%, and relapse rate was 22.6%. For RCHOP-14 group, the incidence of CR, PR and PD was 69.1%, 20.9%, 7.7%, respectively, the response rate was 90.0%, relapse rate was 16.8%, and the results were no significant difference. With the median follow-up of 35.95 months, the 5-year DFS, OS, and PFS of RCHOP-21 compared with RCHOP-14 was 72.2% vs.72.8%, p=0.306; 68.9% vs62.3%, p=0.856; and 53.8% vs. 54.4%, p=0.357,respectively. The most common side effect was bone marrow suppression including 83.6% granulopenia and 46.7% grade III/IV granulopenia, Febrile Neutropenia 24.9%�; 69.1% anemia and 12.6% grade III/IV anemia; 50.6% thrombocytopenia and 11.5% grade III/IV thrombocytopenia. Other side effects included: 18.6% pneumonia, 6.8% interstitial pneumonia, 17.1% other site of infection, 17.5% ALT/AST increasing, 17.4% peripheral neuritis, 13.1% fatigue, 11.9% nausea, 13.1% vomiting, 4.6% oral ulcer. There were no significant difference between the two groups about the above side effects. There were 32 patients (9.1%) in RCHOP-21 and 40 patients (11.5%) in RCHOP-14 delayed the chemotherapy because of severe side effects. High score of IPI, insufficient chemotherapy cycles and relapse during chemotherapy were independent prognosis factors in multivariate analysis.

Conclusion:  RCHOP-14 did not showed superior effective than RCHOP-21. The side effects were similar with prophylactic GCSF in RCHOP-14 regimen. Therefore, RCHOP-21 is still the standard treatment for DLBCL.