Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice.

OBJECTIVE: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. METHOD: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. RESULTS: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. CONCLUSION: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

High prevalence of anaemia and limited use of therapy in cancer patients: a Belgian survey (Anaemia Day 2008).

OBJECTIVES: The aim of this study is to provide relevant and accurate information on prevalence and treatment patterns of anaemia in Belgian cancer patients. METHODS: The Anaemia Day 2008 survey was a single visit, multi-centre, non-interventional study in adult cancer patients under systemic therapy (chemotherapy, hormonal, immunological and/or targeted therapy) and/or radiotherapy. Efforts were made to enroll the maximum number of patients seen in each centre that day. Patients signed an informed consent and relevant data were collected from their files, i.e. disease and disease stage, cancer therapy and anti-anaemic treatment, including transfusions and the use of erythropoietin stimulating agents (ESA). A blood count of each included patient was performed. Haemoglobin (Hb) values (grams per decilitre) were classified into four categories to assess the severity of anaemia, as defined by WHO: no anaemia: Hb ≥ 12 g/dL; mild 10 ≤ Hb ≤ 11.9 g/dL; moderate 8 ≤ Hb ≤ 9.9 g/dL; severe Hb < 8 g/dL. Univariate and multivariate analyses were carried out with anaemia as the dependent variable. RESULTS: A total of 1,403 eligible patients aged 63 ± 13 years (mean age ± SD) were enrolled in 106 oncology or haematology centres. The mean Hb level (± SD) was 11.6 g/dL (± 1.8 g/dL) and the prevalence of anaemia (Hb < 12 g/dL) was 55.7% (95% CI, 53.1-58.3%), respectively, 35.9% mild, 17.8% moderate and 2.1% severe anaemia. Anaemia was more frequent in females than in males, and in patients with haematological malignancies (73.4%) than in those with solid tumours (51.4%; p < 0.001). Anaemia prevalence was higher in hospitalised patients (75.5%) compared to those seen in one-day-clinic (54.3%) or in consultation (33.9%; p < 0.001), and in patients treated with chemotherapy (61.3%) compared to those receiving radiotherapy (34.4%) or hormonal therapy (19.5%; p < 0.001). There was a clear correlation between severity of anaemia and WHO performance status (p < 0.001). Among anaemic patients, 53.1% received no treatment (mean Hb 10.8 ± 0.9 g/dL). Among the anaemic patients who received therapy for their anaemia (mean Hb 9.7 ± 1.1 g/dL), the most frequent treatments were RBC transfusions (42%), ESA (34.6%), transfusions + ESA (12%), ESA + iron (7.9%) and iron alone (3.5%). Comparison to the ECAS survey shows that there has been no major change in attitude towards anaemia management in the last decade. CONCLUSION: This survey shows that cancer-related anaemia is still frequently observed in cancer patients. Even if in our study ESA were used more frequently than about 10 years ago, still a large amount of anaemic patients who could be treated for anaemia according to EORTC guidelines, were not.

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes.

Transfusion dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions. Transfusion dependency is associated with leukemic progression and shorter survival. Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76, and median age at diagnosis of MDS was 74. Patients had received an average of 13.4 ± 7.6 RBC units in the past 4 months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1,550 µg/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of International Prognostic Scoring System (IPSS), French-American-British (FAB), and/or World Health Organization (WHO) status, though chelated patients had received more RBC transfusions (p = 0.014). Iron chelation therapy may be underutilized in transfusion-dependent patients. Undertreatment can be reduced by complementing sound clinical judgment with the generally accepted guidelines of a serum ferritin level >1,000 µg/L and/or two or more RBC transfusions per month for the past year; considering patients on the basis of their IPSS, FAB, and/or WHO status; and individually tailored treatment regimens. Prospective randomized trials are necessary to establish causally the efficacy of iron chelation therapy in MDS.

The use of chemotherapy regimens carrying a moderate or high risk of febrile neutropenia and the corresponding management of febrile neutropenia: an expert survey in breast cancer and non-Hodgkin's lymphoma.

BACKGROUND: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting. METHODS: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL. Data were retrospectively obtained, over a 6-month observation period. RESULTS: The most frequently used regimens in breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced further FN events. Only 1 breast cancer patient received PP, and did not experience a severe neutropenic event. Overall, 30% of chemotherapy cycles observed in breast cancer patients were protected by PP/SP. In 10 NHL patients receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients developing FN. Based on oncologist expert opinion, hospitalization rates for FN (average length of stay) without and with PP were, respectively, 48% (4.2 days) and 19% (1.5 days). Similar rates were obtained from hematologists. CONCLUSIONS: Despite the studied chemotherapy regimens being known to be associated with a moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The observed incidence of severe neutropenic events without G-CSF prophylaxis was higher than generally reported in the literature. The impact on medical resources used is sizeable.

Unclassifiable B-cell lymphoma occurring after necrotizing pneumonia.

We report a case of CD20+ grey zone lymphoma (GZL) with Reed Sternberg cells as an unexpected pathological diagnosis of a destroyed right lower lobe after necrotizing pneumonia. These GZLs show overlapping features of classical Hodgkin's lymphoma and diffuse large B-cell lymphoma. GZLs are a rare specific entity of lymphomas, and the aetiology is unknown. The diagnosis is confirmed by pathological, immunohistochemical and molecular analyses. The optimal treatment is unknown. The prognosis of these patients is poor.

Diagnosis and follow-up of monoclonal gammopathies of undetermined significance; information for referring physicians.

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, The level of monoclonal proteins, increasing levels of the monoclonal component during the first years off follow-up, the percentage of bone marrow plasmocytosis, the dosage of serum free light chains, the presence of immunophenotypically abnormal plasma cells, aneuploidy, and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile.