Importantly, 27 of 101 evaluable patients (27%) entered CR (n=4) or were down-staged as a result of therapy, Of particular interest is that 21 of 64 patients (33%) in Binet stage C before ofatumumab shifted to Binet A or B stage after treatment, mainly due to the recovery of hemoglobin (Hb) levels and platelet counts (106 days) and similar to those reported by Wierda (6 months).10 Information on median overall survival was only available in the Wierda study (14 months), this being slightly longer than in our series (11 months). In conclusion, the present report includes the largest series of patients with poor-prognosis Volinanserin CLL treated with ofatumumab on a routine basis, outside trials. was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line Volinanserin treatment for patients unfit for fludarabine. This study is registered at achieves higher surface density, efficiently activates complement-dependent cytotoxicity (CDC), and shows improved antibody-dependent cell-mediated phagocytosis (ADCC) even when the CD20 expression is low.6C9 The results of a pivotal study10 led to the approval of ofatumumab in October 2009 by the US Food and Drug Administration Volinanserin (FDA) for the treatment of CLL refractory to both fludarabine and alemtuzumab, and likewise, in April 2010, the European Medicines Agency (EMA) issued a conditional marketing authorization for the same indication although this required further clinical data in a daily-life setting.11,12 In this context, the European Research Initiative on CLL (ERIC) conducted a non-interventional, observational phase IV study to determine the safety and efficacy of ofatumumab in patients with pre-treated and poor prognosis CLL in daily practice, outside clinical trials. Methods Diagnosis, patients and study design The diagnosis of CLL was made according to WHO/IWCLL criteria.13,14 Data from patients treated with ofatumumab outside phase II or III ofatumumab-based trials were included in the study. The presence Volinanserin of bulky lymphadenopathy, fludarabine- and alemtuzumab-refractoriness was registered as recorded by participating investigators. Severity of adverse events (AEs) was graded according to the NCI Common Terminology Criteria for Adverse Events (v.3.0). One hundred and three patients from 25 centers in Europe were accrued. The median number of patients treated in each center was 3 (range 1C15). Data collection started on 30 September 2011 and was completed on 24 November 2012. Twenty-seven patients had been previously reported.15 All patients were evaluated on an intention-to-treat basis, independently of the number of cycles of therapy received and whether or not all planned therapy was given. Response to therapy was evaluated according to the IWCLL recommendations,14 changes occurring in clinical stage16 and modifications in individual parameters. Computed tomography (CT) scans were not used to assess disease status. Study end points The main study end points were safety and effectiveness. Progression-free-survival (PFS) was defined as the time from ofatumumab initiation to disease progression or death due to any cause. Overall survival (OS) was defined as the time from ofatumumab initiation to death due to any cause or to last date of contact. PFS and OS were analyzed according to the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazard method. Correlation with clinical parameters and adverse events were summarized using descriptive statistics. 10 Rabbit polyclonal to KCNV2 months; study, 17 cytogenetic information was available, with del(17p) being the only factor associated with a lower response rate in the BF-ref group (ORR: 14% 55%; approx. 50%), most likely due to differences in the time points at which response was assessed, the intention-to-treat analysis, and patients characteristics. Importantly, 27 of 101 evaluable patients (27%) entered CR (n=4) or were down-staged as a result of therapy, Of particular interest is that 21 of 64 patients (33%) in Binet stage C before ofatumumab shifted to Binet A or B stage after treatment, mainly due to the recovery of hemoglobin (Hb) levels and platelet counts (106 days) and similar to those reported by Wierda (6 months).10 Information on median overall survival was only available in the Wierda study (14 months), this being slightly longer than in our series (11 months). In conclusion, the present report includes the largest series of patients with poor-prognosis CLL treated with ofatumumab on a routine basis, outside trials. From this study it can be concluded that results regarding feasibility, toxicity, and effectiveness of ofatumumab in daily life are comparable to those obtained in pioneer phase I and phase II trials.10,16,18 Unfortunately, the response rate and outcome in all these studies, including ours, has been poor. This observation has been confirmed in a randomized phase III trial comparing ibrutinib versus ofatumumab (ORR: 4%; median PFS: 8 months in the ofatumumab arm).20 Ofatumumab, therefore, joins other anti-CD20 monoclonal antibodies such as rituximab and obinutuzumab in the armatorium for CLL treatment. Looking forward to the future, several studies have, not surprisingly, shown much better results in untreated patients.