ALBERT

Description: 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

Description: Abstract 4516 Dengue fever, caused by dengue virus, can cause increased vascular permeability, which leads to a bleeding diathesis or disseminated intravascular coagulation known as Dengue Hemorrhagic Fever (DHF). Hemophagocytocytic Syndrome (HPS) with neurological manifestations is an uncommon presentation of DHF. There are no reports of virus associated with HPS and neurological manifestations in the pediatric literature. Hemophagocytic Syndrome (HPS) is a clinico-pathologic entity characterized by proliferation of T lymphocytes and macrophages leading to cytokine overproduction. HPS may be diagnosed in association with malignant, genetic, or autoimmune diseases. Dengue virus is considered non-neurotropic, however neuroinvansion has been reported. We present the case of a 10 month old female patient who developed DHF, manifested with upper GI bleeding, hypotension and pancytopenia. The infant subsequently developed dengue shock syndrome, with thrombocytopenia, intravascular hemolysis, coagulopathy, elevated transaminase, hyperbilirubinemia, and creatine kinase (CK) of 2,876U/L. She required artificial hemodynamic and blood components support. During her course of illness, she developed ecchymosed, purpuric bullae lesions of the skin in the distal upper extremities. Her IgM ELISA for Dengue virus was positive. Bone marrow aspiration and biopsy was diagnostic for HPS. The patient was initiated on IV steroids and antibiotics therapy. An improvement was noticed on day 8 of illness and was weaned off completely of all artificial support by the day 9. A complete recovery of her hematological, transaminase, billirubin, and coagulation parameters was noticed on day 12. A repeated bone marrow aspirate and biopsy examination was normal. Patient's recovery was significant by muscle weakness (MCG grade ≤3), hypotonia, reduced tendon reflex and increased CK suggestive of possible myositis. The cerebrospinal fluid and magnetic resonance imaging studies of the brain were normal. She was given IV immunoglobulin (500mg/kg) for 2 consecutive days with remarkable neurological improvement including a normal CK (56U/L).She was weaned of steroids completely on day 20.Dengue virus infection was confirmed by a positive serology result at the convalescent stage. On day 23 she had a complete clinical recovery. To our knowledge, this is the first case reported of dengue virus-associated HPS and neurological manifestations in a pediatric patient with DHF. Clinicians should consider that the occurrence of HPS and neurological manifestations in children could de due to dengue virus infection. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction. Ibrutinib is a first-in-class, oral, once-a-day Bruton's tyrosine kinase inhibitor that achieves high overall response rates and durable remissions in patients with chronic lymphocytic leukemia (CLL) including those with high-risk features (unmutated IGHV, TP53 abnormalities, 11q deletion). Survival with continuous single-agent ibrutinib in previously-untreated CLL patients is comparable to an age-matched general population (Figure 1). IBRORS is an observational, retrospective, multicentre study to describe the characteristics and clinical outcomes of patients with CLL treated with single-agent ibrutinib in routine clinical practice in Spain. This present analysis reviews the subset of patients in IBRORS who received ibrutinib as the first-line of treatment. This series includes a significant number of patients with high risk cytogenetic/molecular alterations (del17p/TP53 M), which corresponds with the approved indication for first-line CLL patients in Spain at the time. Methods. Adult patients diagnosed with CLL treated with single-agent ibrutinib in first-line, or at first or second relapse since its commercialization in Spain (between January 2016 to January 2019) were included in the IBRORS study. Clinical characteristics of patients, efficacy and tolerability of ibrutinib as first-line treatment were analyzed here. A Kaplan-Meier analysis was performed for overall survival (OS) and progression-free survival (PFS). Results. 84 patients, from a total of 269 included in IBRORS, received single-agent ibrutinib as first-line treatment. The median age was 71.3 years (range 63-77) at the time of ibrutinib initiation. 56.3% of patients presented with an intermediate/high-risk Rai-Binet stage, and the majority of patients (98.6%) had an ECOG PS of 0-1. 91.7% of patients had at least 1 high risk molecular cytogenetic factor (unmutated IGHV, TP53 abnormalities, 11q deletion or complex karyotype) described in table 1. Baseline comorbidities of patients are described in table 2. Concomitant medication included anticoagulants (9.5% patients; vitamin K antagonist [n=4], Apixaban [n=1] and LMWH [n=3] patients), antiplatelet agents (11.9% patients), and antihypertensives (50% patients). The overall response rate (ORR) was 79.5%; 14/84 (16.6%) achieved a complete response (CR), 14/84 (16.6%) achieved CR unconfirmed, 27/84 (32.14%) achieved a partial response (PR) and 12/84 (14.2%) a PR + lymphocytosis. The median PFS and OS were not reached, and the estimated PFS at 24 months was 84.5% (73.4-95.6%). OS and PFS curves are represented in figure 2. The PFS of each patient subgroup with high-risk cytogenetic characteristics was similar to that of all patients in the first-line cohort: del17p/TP53 mutation (HR = 0.963 [95% CI 0.188-4.928]; p = 0.964), del11q (HR = 0.042 [95% CI 0.000-682.736]; p=0.521), unmutated IGHV (HR = 0.391 [95% CI 0.110-1.394]; p = 0.148). The median duration of exposure to ibrutinib was 17.3 (11.9-25.6) months. Dose reduction of ibrutinib occurred in 17/84 (20.2%) patients, 8/84 (9.52%) due to toxicity (4 hematologic toxicity and 4 non-hematologic toxicity). 27/84 (32.1%) patients had temporary interruption of treatment. 15/84 (17.8%) patients permanently discontinued ibrutinib including 6 (7.14%) patients due to progression, 4 (4.76%) due to toxicity and 5 for other reasons. Safety: 49/84 (58.3%) patients developed at least one adverse event (AE), while 12/84 (14.2%) patients developed at least one serious adverse event (SAE). Twelve (14.3%) patients reported at least one haematological toxicity while 53 patients (63.1%) recorded at least one non-haematological toxicity. Only 1 patient experienced grade 3 atrial fibrillation, which did not lead to discontinuation. The most common AEs are described in table 3. Conclusion. This population of previously-untreated CLL patients, enriched for high-risk genomic features, reflects the initial approval of ibrutinib for the treatment of first-line patients with del17p in Spain. Single-agent Ibrutinib as the first-line treatment in this real world population was effective regardless of risk factors and well tolerated, with a low rate of discontinuation due to toxicity. Findings are consistent with those reported in clinical trials. Disclosures Loscertales: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Arguiñano:AbbVie: Honoraria; Janssen: Honoraria; BMS-Celgene: Honoraria; Novartis: Honoraria. Hernandez-Rivas:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Pérez Persona:Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Jannsen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Takeda: Consultancy. Loriente:Janssen Cilag: Current Employment. Villanueva:Janssen Cilag: Current Employment.