Prospective, Observational Study to Assess the Safety of Rituximab(R) in Combination with Chemotherapy in Patients with Previously-Untreated or Relapsed or Refractory B Cell-Lineage Chronic Lymphocytic Leukaemia (B-CLL): Final Results
Authors: Giraldo Pilar , Lopez Andres , Rios Eduardo , Carbonell Felix , Lopez Javier , Ramírez Angel , Rodriguez Alicia , Gomez Marta , Garcia Ricardo , Baltasar Patricia , Duran Maria , Perez Raul , Garcia Maria , Márquez José Antonio , De la Serna Javier 
Published: October 2019

Abstract
Aim and Background: MABERYC non-interventional study was designed to characterize the type, severity and frequency of all adverse events (AEs)/serious-AEs (SAEs) occurring on-treatment and in the year following rituximab infusion. Secondary objectives included response rate (CR/PR) and to evaluate the clinical utility and the validity of a specific comorbidity scale (CoLLECT scale) for B-CLL patients, planned to recognize patients who may benefit from some special pharmacological approach.
Methods: Between November 2010 and February 2012, data were collected prospectively from B-CLL patients, in 47 Spanish hospitals, starting a new treatment with an R-based chemotherapeutic scheme in accordance with normal clinical practice at the time of enrollment. Safety analyses were conducted by closely monitoring patients throughout the study. AEs and SAEs were tabulated by NCI-Common Toxicity Criteria (NCI-CTC), v4.0. In order to validate the CoLLECT scale, specifically designed for this study, assessment of comorbidity was planned at baseline and 12 months following treatment finalization, using three subscales (low [0-3], moderate [4-7] and high [>7]) with ten different indexes. Changes were categorized in improvement (reduction ≥2), no changes (variation <2) and worsening (increase ≥2).
Results: A total of 218 patients have been enrolled, 108 and 110 pts in the first-line and pre-treated arm, respectively. The median age (range) of the whole series was 69 (r: 39–87) years. ECOG status varied across the two groups, with a ≤1 ECOG status score of 99%, and 84% of first-line and pre-treated patients, respectively. The baseline characteristics on both arms are shown in Table 1.
Figure 1 Figure 1.
1448 AEs were reported on treatment, 50% of them considered as drug-related. The most frequently related-AE in first-line and pre-treated arm included: neutropenia (34/30%); fever (18/12%); nausea (15/11%); thrombocytopenia (10/17%), febrile neutropenia (FN) (10/9%), and anemia (7/16%). Overall, the treatment was well tolerated and the toxicity profile differed according to the treatment arm (Table 2). Treatment discontinuations due to related-AEs in the first-line and pre-treated arm was of 9 and 11% on-treatment, fatal AEs occurred in 3% and 4%, respectively.
Figure 2 Figure 2.
In the overall population by IWG response criteria, the best response on treatment was CR in 28% and PR in 30% of patients (nPR in 4% of patients). Although, based on fairly different number of patients by scheme that preclude a completely valid statistical comparison, the complete and partial response rate (CR/PR) in the first-line arm was as follows: BR (50/31%), FCR (43/25%), R+others (29/43%) and ClbR cohort (23/46%), while in the pre-treated arm the response rate was higher in the BR (20/16%), followed by FCR (19/24%), R+others (5/52%) and ClbR cohort (15/40%).
Mean CoLLECT score was higher in older patient, higher ECOG, previously treated and those receiving less aggressive treatments. Changes in CoLLECT showed CR could be associated to improvement in comorbidity. CR was reached by 53% of patients with COLLECT improvement, 47% without changes, and 32% worsening.
Conclusion: In this unselected group of B-CLL patients taken from normal clinical practice, the AEs frequency was related to immunochemotherapy scheme as well as the stage of treatment. Rituximab seems an effective and relatively safe option when added to any chemotherapy regimen. With the help of the CoLLECT scale, which is related with patient´s profile, treatment regimen prescribed, CR and AEs, patient’s co-morbidity can be assessed and assist on decision-making about the intensity of the inmmunochemotherapy regimen to be prescribed.

Disclosures
No relevant conflicts of interest to declare.