Koen Van Eygen

Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: The ADAGIO study

Imatinib mesylate (imatinib) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong, patient adherence is critical. The ADAGIO (Adherence Assessment with Glivec: Indicators and Outcomes) study aimed to assess prospectively over a 90-day period the prevalence of imatinib nonadherence in patients with CML; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence; and to examine whether treatment response is associated with adherence levels. A total of 202 patients were recruited from 34 centers in Belgium, of whom 169 were evaluable. One-third of patients were considered to be nonadherent. Only 14.2% of patients were perfectly adherent with 100% of prescribed imatinib taken. On average, patients with suboptimal response had significantly higher mean percentages of imatinib not taken (23.2%, standard deviation [SD] = 23.8) than did those with optimal response (7.3%, SD = 19.3, P = .005; percentages calculated as proportions x 100). Nonadherence is more prevalent than patients, physicians, and family members believe it is, and therefore should be assessed routinely. It is associated with poorer response to imatinib. Several determinants may serve as alert signals, many of which are clinically modifiable.

Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

BACKGROUND Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especially those classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1). METHODS Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centers in Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). RESULTS Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 μg/L. Of the 80 chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox following deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patients chelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiac mortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1 years for non-chelated patients (p<0.001). For patients chelated ≥6 m or patients classified as adequately chelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusion intensity (HR=1.08, p=0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m (HR=0.24, p<0.001). CONCLUSION Six or more months of adequate ICT is associated with markedly better overall survival. This suggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS.

A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma.

This international, multicentre phase II study was conducted to assess ofatumumab, a human anti‐CD20 monoclonal antibody, in patients with relapsed/progressive diffuse large B‐cell lymphoma (DLBCL) who were ineligible for autologous stem cell transplantation (TI) or who had relapse/progression after transplantation (PT). Eighty‐one patients received ofatumumab 300 mg intravenously (IV) on Day 1, followed by seven weekly IV infusions of 1000 mg. Patients in the TI and PT groups had received a median of 3 (range, 1–7) and 5 (range, 2–7) prior therapies, respectively. One‐third of patients did not respond to the last prior therapy, and 53% had failed two or more rituximab‐containing therapies. Overall response rate was 13% for the TI group (seven partial responses) and 8% for the PT group (two complete responses). Median progression‐free survival was 2·6 months, and median duration of response was 9·5 months. The most common Grade 3–4 adverse events were neutropenia (11%), leucopenia (6%), lymphopenia (6%) and thrombocytopenia (6%). Sixteen deaths have been reported, with disease progression as the most common cause of death. In conclusion, ofatumumab monotherapy was well tolerated and provided clinical benefit to some DLBCL patients in this study. This trial was registered at www.clinicaltrials.gov (NCT00622388).

Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

Purpose The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.

Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment.

We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in‐depth cognitive evaluation within a comprehensive geriatric assessment (CGA).

Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment.

Recent research in the field of cancer‐related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors.

Implementation of uHear™ - an iOS-based application to screen for hearing loss - in older patients with cancer undergoing a comprehensive geriatric assessment

OBJECTIVE Validation of uHear™ as a screening tool to detect hearing loss in older patients with cancer without a known diagnosis of presbycusis, as part of a Comprehensive Geriatric Assessment (CGA). MATERIALS AND METHODS Patients (≥70 years) with a histologically confirmed diagnosis of cancer, were enrolled at the time of CGA screening. Patients were evaluated by uHear™, which was compared to conventional audiometry as gold standard. We defined a pure-tone average (PTA) of ≥40dB HL as the pass or fail screening cut-off. Validation of uHear™ was defined in terms of diagnostic accuracy through Receiver Operating Characteristics (ROC)-analysis. To accept uHear™, we estimated that the Area Under the ROC-curve (AUC) had to differ significantly from 0.50 with an AUC of at least 0.70. The Whispered Voice Test and Hearing Handicap Inventory for the Elderly were also administered. RESULTS Thirty-three patients consented for participation. In one patient, the results of one ear were excluded from the analysis as the patient was documented with a known hearing disorder in that ear. Significant hearing loss, defined by a PTA of ≥40dB HL calculated from the air conduction thresholds at 0.5, 1.0 and 2.0kHz, was found in 15.4% of tested ears. uHear™ showed excellent diagnostic accuracy with an AUC±SE of 0.98±0.14. It provided maximum sensitivity (100.0%) but poor specificity (36.4%) at our predefined cut-off score of ≥40dB HL. CONCLUSION uHear™ can be implemented as a screening tool to detect hearing loss in older patients with cancer within a CGA.

The use of uHear™ to screen for hearing loss in older patients with cancer as part of a comprehensive geriatric assessment

Abstract Objective: We previously validated uHear™ to screen for hearing loss in older patients with cancer without a known hearing loss, as part of a comprehensive geriatric assessment (CGA). In view of low specificity, we tested a new modified uHear™ scoring system as described by Handzel. Methods: Patients, aged ≥70 years, were evaluated by uHear™ and conventional audiometry, which is considered the gold standard, as part of a CGA. The pass or fail screening cut-off for uHear™ was defined as having ≥2 consecutive hearing grades starting from the moderate–severe threshold zone ranging from 0.5 to 2.0 kHz (modified Handzel-uHear™ scoring system). To accept the modified Handzel-uHear™ as screening tool, it was predefined that the combined sensitivity (S) and specificity (Sp) of the test (S + Sp/2) was at least 80% and that an actual combined (S + Sp)/2 of 90% would be found. Results: Ninety ears (45 subjects) were tested. Of those ears, 24.4% were identified as impaired by conventional audiometry. Modified Handzel-uHear™ identified 26.7% of tested ears as impaired. The combined (S + Sp)/2 of the modified Handzel-uHear™ was calculated as 77.5%, while in previous cohort, this was retrospectively calculated as 94.6%. A new uHear™ scoring system was proposed and tested in current and previous cohort. A (S + Sp)/2 of 80.2 and 78.8%, respectively, were obtained. Conclusion: uHear™ is a feasible tool for use within the CGA and shows promising results. However, further research is warranted to optimize the cut-off method before it could be routinely implemented within geriatric oncology.

Results from the Belgian mantle cell lymphoma registry.

Introduction: Mantle cell lymphoma is a B-cell non-Hodgkin’s lymphoma characterized by a t(11;14), resulting in overexpression of cyclin D1. Conventional chemotherapy obtains frequent (but short) remissions, leading to a poor median overall survival (OS) of 3–5 years. To obtain more information about the prevalence and current treatment of Mantle cell lymphoma (MCL) in Belgium, we collected data in a Belgian registry of MCL. Materials and methods: All Belgian MCL patients, t(11;14) and/or cyclin D1 positive, seen in hematology departments over a one-year period (April 2013–March 2014) were included. Data about patient characteristics, histology, treatment lines, and response were compiled and retrospectively analyzed. Results: Four hundred and four patients were included with a median age at diagnosis of 64 years (range 23–96 years) and a male predominance (72%). For 2013, we calculated a prevalence of at least 36.2 per million and an incidence of at least 7.0 per million in the Belgian population. Characteristics at diagnosis involved lymphadenopathy (82%), splenomegaly (44%), B-symptoms (39%), and hepatomegaly (10%). Bone marrow invasion was present at diagnosis in 77%. Stage at diagnosis was advanced in the majority of cases. The median number of treatment lines was 1. Type of first line treatment included a combination of anthracyclin and cytarabine-based regimen (34%), anthracyclin (39%), and other. Rituximab was used in 88% of first line treatments. In 44% first line treatment was followed by autologous stem cell transplantation. Conclusion: The analysis of this Belgian MCL registry provides insight in the epidemiology, demographics, and current treatment of our Belgian MCL population.

Obinutuzumab plus Lenalidomide (GALEN) for the treatment of relapse/refractory aggressive lymphoma: a phase II LYSA study

Roch Houot ● Guillaume Cartron ● Fontanet Bijou ● Sophie de Guibert ● Gilles A. Salles 4 ● Christophe Fruchart ● Krimo Bouabdallah ● Marie Maerevoet ● Pierre Feugier ● Steven Le Gouill ● Hervé Tilly ● Rene-Olivier Casasnovas ● Cécile Moluçon-Chabrot ● Eric Van Den Neste ● Pierre Zachee ● Marc Andre ● Christophe Bonnet ● Corinne Haioun ● Achiel Van Hoof ● Koen Van Eygen ● Lysiane Molina ● Emmanuelle Nicolas-Virelizier ● Philippe Ruminy ● Franck Morschhauser