[A rapidly growing skin lesion on the sternum]. / Een snelgroeiende huidafwijking op het borstbeen.

This case involves a man with a medical history of multiple myeloma and osseous metastasis of prostate carcinoma. He presented with a progressively growing red tumor on his chest for the past three weeks. Histopathological examination revealed many atypical CD0138-positive plasmablastic cells, which matches a cutaneous manifestation of multiple myeloma.

Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression: a prospective, open-label, multicenter, randomized, phase 3 study.

Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size. In general, improvement occurred after 6-12 months of maintenance only and was independent of the World Health Organisation performance at baseline. Patients treated with MPR-R reported clinically relevant worsening of diarrhea, and patients treated with MPT-T reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least three months reported clinically meaningful improvement in global QoL and role functioning at six months, remaining stable thereafter. There were no clinically meaningful deteriorations, but patients on thalidomide reported clinically relevant worsening in neuropathy. In general, HRQoL improves both during induction and maintenance therapy with immunomodulatory drugs. The side effect profile of treatment did not negatively affect global QoL, but it was, however, clinically relevant for the patients. (Clinicaltrials.gov identifier: NTR1630).

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.

Human soluble TRAIL/Apo2L induces apoptosis in a subpopulation of chemotherapy refractory nodal diffuse large B-cell lymphomas, determined by a highly sensitive in vitro apoptosis assay.

Resistance to chemotherapy in therapy-refractory diffuse large B-cell lymphomas (DLBCL) is related to inhibition of the intrinsic apoptosis pathway. Human soluble tumour necrosis factor (TNF)-related apoptosis-inducing ligand (hsTRAIL/Apo2L) induces apoptosis via the alternative, death-receptor mediated apoptosis pathway and might be an effective alternative form of therapy for these lymphomas. This study investigated whether hsTRAIL/Apo2L could actually induce apoptosis in isolated lymphoma cells of DLBCL biopsies of patients with chemotherapy-refractory DLBCL. Twelve out of a total of 22 DLBCL samples were sensitive to hsTRAIL/Apo2L. These sensitive lymphomas included seven clinically chemotherapy-refractory lymphomas. Furthermore, hsTRAIL/Apo2L induced apoptosis in DLBCL cells and in B-cell lines that showed high expression levels of inhibitors of the intrinsic apoptosis pathway: Bcl-2 and/or X-linked inhibitor of apoptosis (XIAP). hsTRAIL/Apo2L-sensitive lymphoma cells showed expression of the TRAIL receptors R1 and/or R2 and absence of R3 and R4. We conclude that hsTRAIL/Apo2L induced apoptosis in a subpopulation of chemotherapy-refractory nodal DLBCL and that disruption of the intrinsic apoptosis-mediated pathway and expression of Bcl-2 and XIAP did not confer resistance to hsTRAIL/Apo2L-induced apoptosis in DLBCL. Thus, based on our results, further exploration of hsTRAIL/Apo2L as an alternative treatment for patients with chemotherapy-refractory DLBCL should be considered.

Cost analysis of common treatment options for indolent follicular non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: We assessed direct health care costs associated with the most commonly prescribed treatments for indolent follicular non-Hodgkin's lymphoma (FL). DESIGN AND METHODS: New and previously diagnosed FL patients (>or=18 years) known during 1997-1998 to 15 Dutch hospitals were selected for inclusion. Each patient was followed for 3 years, and resource use associated with each of the treatments, including watchful waiting, was recorded. The hospital perspective was adopted. Unit costs were based on 2003 price levels. RESULTS: Two hundred patients were included of whom 75% underwent one or more treatments during the 3-year data collection period [25% were not treated because of a watchful waiting strategy (10%) or complete remission (15%)]. Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean (median) per patient cost of 45,326 euro(44,237; n=7) and 18,866 euro (16,532; n=9), respectively (up to discharge only). Intravenous fludarabine cost 10,651 euro (9,995; n=33), rituximab (10,628 euro; 10,124; n=7), and CHOP 7,547 euro (5,833; n=42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for cylophosphamide, vincristine and prednisone of 5,268 euro (2,644; n=58), for radiotherapy of 4,218 euro (4,313; n=52), and for chlorambucil of 2,476 euro (1,098; n=53). INTERPRETATION AND CONCLUSIONS: This study presents information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning, given the high costs of new treatment modalities.