Rituximab in Combination with Cyclophosphamide, Mitoxantrone, Vincristine and Prednisone (R-CNOP) As First Line Regimen in Elderly Patients with Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a treatable and potentially curable malignancy that is increasing in prevalence in the elderly. Because of geriatric considerations including functional status and comorbidities and increased toxicity concerns, older patients are sometimes given reduced dose therapy. Mitoxantrone has a broad anti-tumour activity including lymphoma with potentially less cardiotoxicity than doxorubicin, which may be of particular importance in the treatment of elderly aggressive lymphoma patients.

This study's objective was to evaluate the efficacy and safety of R-CNOP (rituximab plus cyclophosphamide/mitoxantrone/vincristine/prednisone) combination regimen at standart doses in elderly patients with newly diagnosed diffuse large B-cell lymphoma. Mitoxantrone was given at the dose of 12 mg/m². Twenty-four patients were enrolled. All patients had an ECOG performance status ≤ 2. Twenty-two patients (91.7%) had several comorbidities, the most common were cardiac diseases and hypertension (56%). Excluding one patient and with a borderline heart function (ejection fraction of 50%), all patients had an ejection fraction (EF) of ≥60%.

The median age was 71 years (50-78) and 20 (83%) were female. Nineteen (79.2%) patients were stage III-IV and 15 (62.5%) patients had high-intermediate or high aa-IPI score. Thirteen patients (52%) had Ki-67 proliferation index > 80%. Three patients was myc positive. Twelve were non-germinal center phenotype. Median number of R-CNOP cycles administered to the patients was 6 (3-6). Treatment response was evaluated with PET-CT before and after the treatment. Of 24 patients, 19 (79.2%) had complete response, 3 (12.5%) had partial response, 2 (8.3%) had refractory/progressive disease. Two patients who had refractory/progressive disease received salvage chemotherapy and achieved complete response. The median follow-up was 18.78 (5.6-82.8) months. The median time to progression for responding patients (n=3) was was 14.3 (4.5-79.1) months. Median DFS and OS were not reached. Main toxicity was hematological. Grade ≥3 hematologic toxicity occurred in 13 patients: neutropenia (37.5%), thrombocytopenia (8.4%), and anemia (8.3%). Four (16.7%) patients developed febrile neutropenia and two patient developed pulmonary thromboembolism during therapy. Treatment cycle postponed in 11 (45.8%) patients without dose reduction because of hematological toxicity. Nineteen (79.2%) patients received G-CSF primary prophylaxis. After the treatment EF decreased (≤50%) only in two patients, who had coronary artery disease before the treatment. The patient who had borderline EF had stable EF after the treatment.

R-CNOP was shown to be an effective and safe regimen in elderly patients with diffuse large B-cell lymphoma. The majority of the patients had long term disease control. Hematological toxicity was common.