Treatment of Diffuse Large B Cell Lymphoma with CHOP and Rituximab. Results of a Multicenter Study with 236 Patients.
Authors: De la Serna Javier , Ayala R. , Canales M. , Giraldo P. , de la Cruz-Mora M. , Rueda A. , Montalban C. , Queizan J. , Garcia-Vela J. , Feliu F. , Calle C. , Hernandez B. , Hernandez R. , Solano F. , Peñalver J. , Ojanguren J. , Sanchez-Guilarte J. , Morante C. , Nicolas C. , Roman A. , Palomera L. , Diaz-Mediavilla J. 
Published: October 2019

Abstract
Introduction: The treatment of diffuse large B cell lymphoma (DLBCL) is based on anthracyclin containing regimens. The CHOP regimen is considered the standard of chemotherapy, although immunochemotherapy regimens appear to be more effective. Rituximab (R), when combined with CHOP or CHOP-like regimens, improve the complete remission (CR) rate and survival in elderly and low risk young patients. Nevertheless, the CR rate and survival continues to be predicted by patient’s international prognostic index (IPI). R-CHOP has been claimed to be a new standard of treatment for DLBCL and adopted in the common practice.
Purpose: In this study we aimed to analyze prospectively the results of R-CHOP, used as a standard of care for DLBCL patients irrespectively of age or IPI.
Methods: Between 1/2001 and 1/2005, 236 patients with DLBCL recruited from 25 institutions, including community-based and University Hospitals, received upfront therapy with R-CHOP. Patients were required to have no contraindications for antineoplastic therapy and give consent. They were given 3–4 courses for localized, and 6–8 courses for advanced disease. Rituximab was given at 375 mg/m2 the first day of each course. R-CHOP cycles were given every 21 days, except for 5 centres giving cycles every 14 days. Radiation therapy was given for bulky (> 7 cm) areas. Prophylaxis, supportive measures and hematopoietic factors were given according to local policies. Response to therapy was evaluated 3 months after the completion of treatment.
Results: There were 109 males and 127 females, median age 62 years (range 18–84). The number of IPI factors at diagnosis were: 0–1 in 32%; 2 in 28%; 3 in 19% and 4–5 in 21% of patients. B-symptoms, bulky disease > 7 cm, high b2-microglobulin and low albumin were present in 47%, 31%, 33% and 31% of patients, respectively. R-CHOP 21 was given to 85%, and R-CHOP 14 to 15% of patients. Dose intensity was maintained in 74% of patients, and 88% completed treatment. Involved-field radiation was given to 17% of cases. The overall CR rate was 82.2%. Failures due to lymphoma resistance or toxicities were 14.1%. According to the IPI score, the CR rate was as follows: 0–1: 90.5%; 2: 85.5%; 3: 72.2%; and 4–5: 73%. After a median follow-up of 15.4 months (range 1 to 53 months), the progression free survival (PFS) and overall survival (OS) are 74.4% and 84%, respectively. The IPI score at diagnosis influenced both PFS and OS. The PFS for patients with an IPI score of 0–1, 2, 3 and 4–5 were 85.5%, 83.0%, 72.2% and 66.7%, respectively. The OS according to the IPI score was 95.2%, 90.9%, 72.2%, and 63.2%, respectively. Patients receiving R-CHOP 14 showed a trend to improved survival. The main causes of death were lymphoma progression (64%), infections (15%), second neoplasms (9%), thrombosis (6%) and cardiac failure (6%).
Conclusions: The R-CHOP regimen is well tolerated and achieves improved results and outcome in an unselected population of DLBCL patients. The improved survival in this series require confirmation with longer follow up. The IPI score retains a major prognostic significance for response and survival.