Treatment of Indolent Lymphomas with 3 CNOP- 4 COPB.
Authors: Murillo Edgar , Nambo Maria , Aviles Agustin , Neri Natividad , Talavera Alejandra , Gonzalez Martha , Castañeda Claudia , Cleto Sergio , Huerta Judith 
Published: April 2020

Abstract
Frequently recurrences and progressive resistance to chemotherapy characterize indolent lymphomas. The use of anthracyclines has been improved the response rate and the disease free survival, however, its use in elderly patients is controversial because the related toxicities. We analyze the use of a chemotherapy regimen with a short course of anthracycline.
Material and Methods: We included patients with untreated indolent lymphomas according to the WHO classification. The chemotherapy regimens were 3 cycles of CNOP (cyclophosphamide 600 mg/m2 day 1, mitoxantrone 10 mg/m2 day1, vincristine 1.4 mg/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 21 days, followed by 4 cycles of COPB (cyclophosphamide 800 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, a bleomycin 10 U/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 14 days.
Results: In an intent to treat 75 patients were valuable, 37 females and 38 males, median age was 56 (range 28–84), the histological variants were: follicular grade 1 and 2 (45 patients), lymphoma/leukemia of small well differentiated lymphocytes (6 patients), mantle cell lymphoma (1 patient), nodal marginal zone lymphoma (4 patients), lymphoplasmocytic lymphoma (1 patient), indolent lymphoma not otherwise characterized (12 patients), 61 patients (81.3%) had bulky disease, 57 patients (76%) had advanced disease (stage III and IV). According to the IPI: low risk (28 patients), low intermediate (21 patients), high intermediate (14 patients), and high (12 patients). A total of 488 cycles were administrated, 82 (16.8%) cycles had hematologic toxicities: 30 cycles grade 1, 29 cycles grade 2, 18 cycles grade 3, and 5 cycles grade 4. Filgrastim was needed in 20 patients (43 cycles). 58 patients had gastrointestinal toxicity (29 grade1, 26 grade 2, 3 grade 3), 61 patients had neurological toxicity (47 grade 1, 13 grade 2, 1 grade 3). 14 patients (18.7%) required hospitalization, 7 patients due to toxicity related chemotherapy and 6 due to tumor progression. The overall response rate was 84% (63 patients): Complete response 33 patients (44%), unconfirmed complete response 6 patients (8%), partial response 24 patients (32%). Failure to treatment occurred in 11 patients (14.7%). Adding radiotherapy 12 more patients were converted to complete response for a total of 45 patients (60%). With a median of follow up of 24 months (range 3–62 months) 10 patients (13.3%) relapsed, 13 (17.3%) patients died (8 due to tumor progression and 3 related to toxicity of the regimen). The actuarial 5-year disease free survival was 71% and the overall survival 86%.
Conclusions: This chemotherapy regimen provides an effective alternative for the treatment of indolent lymphomas even in advanced or bulky disease. This regimen is well tolerated for elderly patients and has a good safety profile. It is necessary a long time of follow up to establish the importance of the regimen in free disease survival and in overall survival.