PB1898 SAFETY AND EFFECTIVENESS OF CHLORAMBUCIL‐OBINUTUZUMAB IN THE FRONT LINE TREATMENT OF UNFIT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: REAL‐LIFE DATA FROM ANDALUSIAN LYMPHOID NEOPLASM GROUP (GRANEL)
Authors: Puerta Puerta J.M. , Martín Palanco V. , Badiola J. , Fernández de la Mata M. , Ortiz Pareja M. , Martínez Quesada M.J. , Rodríguez Fernández A. , De la Cruz Vicente F. , Ferrer Chaves C. , Lorente de Uña S. , Moya Rodríguez R. , García Pérez M.J. , García Martín P. , García Cabrera I.M. , Berruezo Salazar M.J. , Fernández Jiménez D. , Ríos Herranz E. 
Published: June 2019

Background:The Chlorambucil‐Obinutuzumab (CI‐O) is a therapeutic regimen for unfit patients with chronic lymphocytic leukemia (CLL), whether due to old age or with comorbidities that keep them from receiving intensive chemotherapeutic treatment. Results of the CLL11 clinical trial position this treatment as a first‐line alternative with 1A category because of its safety and efficacy among these patient.Aims:To analyze our real‐life experience in terms of safety and effectiveness in first‐line treatment with the CI‐O combination in elderly or unfit patients with CLL.Methods:This retrospective study included 69 unfit CLL patients from 12 hospitals from the GRANEL group (Andalusia, Spain) with first‐line treatment out of clinical trial from May 2016 to February 2019 following a CI‐O protocol. Before treatment, patients were assessed using the comorbidities scale CIRS (Cumulative Illness Rating Scale score). Demographic data, illness, complications, and responses to treatment are analyzed.Results:Baseline features are shown in table 1. At the time of analysis, 9 out of 69 patients of the series are still in treatment. From the remaining 60, 48 (80%) completed 6 programmed cycles, 2 (3.3.%) received 5 cycles, 3 (5%) received 4 cycles, 2 (3.3%) received 3 cycles and 5 (8.3%) only 1 cycle (2 deaths after the first cycle, 1 infusion reaction that led to ceasing treatment, 1 progression and later second‐line and a decision to stop treatment by the medical team due to stable illness after cycle 1). 69.6% of patients received treatment without infusion reaction. 21 infusion reactions occurred (30.4% of patients), 95% reported on the first day of the first cycle, being 90.4% of grade 1‐2. Only 1 suspension of treatment for infusion reaction grade 4 was reported, and 1 death occurred due to acute pulmonary edema on the second day in patient with severe heart failure prior to treatment. 55% of patients suffered some type of grade III‐IV toxicity: 40.5% neutropenia and 11.6% thrombocytopenia, 3 (4.3%) cases of grade III‐IV infection and 2 cases of liver toxicity (3%). Response at end of treatment (EOT) was assessed on 51 patients: overall responses (OR) rate was 90.2%. Complete remission (CR) 62.7% and partial remission (PR) 27.5%. 1 patient (2%) stable disease (SD) and 4 (7.8%) progressions occurred. Progression rate throughout the follow‐up was 21%. The median progression free survival (PFS) was not reached after a median follow‐up of 10 months. Estimated PFS at 12 months was 82% and 55.5% at 24 months. MRD in peripheral blood (PB) among 34 patients (49.3%) was evaluated at EOT: 64.7% negative and 35.3% positive. The median time to next treatment was not reached. 81% of patients continue without receiving second‐line treatment, and among the patients who progressed, 42% have still not initiated second line treatment. 7 deaths occurred (10%): 2 respiratory infections, 1 spontaneous bacterial peritonitis in a patient with HCV, 1 fulminating liver failure of unknown origin, 1 metastatic bladder cancer, 1 acute pulmonary edema, and 1 pulmonary thromboembolism. Median overall survival (OS) has not been reached. Estimated OS at 12 months is 90.2% and 83% at 24 months.Summary/Conclusion:Our data confirm the effectiveness of CI‐O regimen in fragile CLL patients in real‐life, with OR rates of 90%, and CR rates of 63%. 65% of patients achieved negative MRD at EOT in PB. Good safety profile and well‐tolerated regimen with low rate of serious infections and grade I‐II infusion‐related reactions which do not generally lead to treatment cessation.image