R-CHOP Modified with Pegilated Lyposomal Adriamycin in Elderly Diffuse Large B-Cell Non Hodgkin’s Lymphoma (DLBC-NHL) Therapy: An Attempt To Reduce Toxicity in Patients with Comorbidity.
Authors: Giordano Giulio , Dell’Olio Matteo , Piano Silvia , Farina Giuliana , La Sala Antonio , Colaprete Daniele , Cascavilla Nicola , Storti Sergio 
Published: November 2019

Abstract
The Combination of Rituximab and CHOP (R-CHOP) is the golden standard in young and elderly NHL therapy, safe and effective. We included pegylated lyposomial Adriamycin (Caelyx®) instead of conventional Adriamycin in R-CHOP regimen in order to reduce myocardic and organ toxicity and to enhance doxorubicin uptake in tumour mass in advanced stage DLBC-NHL of elderly patients with comorbidity. This study is a retrospective study including patients of two haematology centers. We analyzed 34 DLBCNHL patient treated with R-CCOP (Rituximab 375mg/sqm day 0, Caelyx® 30 mg/sqm day 1, cyclophosphamide 750 mg/sqm day 1, Vincristine 1 mg/sqm day 1, Prednisone 100 mg/day, days 1–5, recycle every 21 days). The median number of administered cycles was 6 (Range 4–11). G-CSF was administered according to international guidelines Their median age was 74.5 years old (Range 65–87), M/F:20/14, 19/34 (55%) patients presented stage III– IV disease. 8 (23%) had B symptoms and 11 (32%) extranodal disease.12/34 (35%) patients had IPI high-intermediate and 11/34 (32%) high. 17/34 (50%) showed comorbidity (hepatitis C, NIDDM, severe hypertension, aortic valve disease, atrial fibrillation, chronic renal failure). Median follow-up was 26 months (Range 9–36). Overall (OS) and progression-free survival (PFS) at 36 months were calculated using Kaplan-Mayer method. After R-CCOP therapy we obtained the complete remission in 24/34 (70%) of patients, a very good partial remission in 2/34 (5%). The disease progressed in 3/34 (8%). Five out of 34 (14%) dead (3 of these for disease progression). No severe treatment-related toxicities were observed, except G3-G4 WHO neutropenia in 17 patients (50%) and cardiotoxicity in 2 patients (6%) with pre-existing cardiopathy (bradycardia and atrial fibrillation with high heart rate respectively). Myocardial function was evaluated by 2D echocardiogram before and after chemotherapy treatment and was not impaired by pegylated lyposomial Adriamycin administration. 3% of patients presented severe mucositis and 9% non-fatal infections. We did not observe any thrombocytopenia, In our study OS and EFS at 36 months were respectively 83.7% (95%CI 70.4–97%) and 56% (95%CI 27–85%).Non-responding patients had extranodal, stage IV disease with B symptoms. Nevertheless, they maintained chemosensitivity to a second-line therapy. In elderly B-NHL patients with advanced stage of disease and comorbidity, R-CCOP seems to be safe, feasible and effective. These results confirm and improve in a larger cohort of patients those reported by Zaja, Tulpule and Coiffier in their previous series (see table).
Zaja et al Tulpule et al Giordano et al Coiffier et al Treatment R-COP-Caelyx x6 R-COP-Caelyx x8 R-COP-Caelyx x4-11 R-CHOP x8 * in 2 pts with preexisting cardiopathy Patients 29 19 34 202 Caelyx mg/sqm 30 40 30 \ Doxorubicin mg/sqm \ \ \ 50 Age (median) 69 51 74.5 69 IPI (L/IL) 38% 47% 32% 46% IPI IH/H 62% 53% 68% 54% OR 76% 100% 76% 82% CR 59% 80% 71% 76% 2y EFS 65.5% NA (56% 3y) 60% TRM 0 0 0 12/202 (6%) Grade III/IV toxicity Neutropenia 86% 68% 50% 91% Thrombocytopenia 3% 5% 0% NA Mucositis 3% 0% 3% 3% Infection 3% 0% 9% 12% Cardiotocicity 0% 0% 6%* 8%