melphalan and Thromboembolism

Although haematological toxicities, such as anaemia, are common in multiple myeloma (MM), no clear consensus exists on the use and impact of erythropoiesis-stimulating agents (ESA) on outcomes in MM. This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA (Velcade(®) as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone) study of bortezomib plus melphalan/prednisone (VMP, n = 344) versus MP (n = 338) in previously untreated MM patients ineligible for high-dose therapy, and evaluates the impact of ESA use or red-blood-cell (RBC) transfusions on outcomes and thromboembolic risk. Incidence of haematological toxicities was similar with VMP and MP; similar rates of interventions and associated complications (e.g. bleeding, febrile neutropenia) were observed. Two hundred thirty three patients received ESA; 204 had RBC transfusions. Frequency of thromboembolic events was low and not affected by ESA use. Median time-to progression (TTP) was similar between ESA/non-ESA [hazard ratio: 1·03 (95% confidence interval 0·76-1·39); P = 0·8478] in both arms (VMP: 19·9/not reached; MP: 15·0/17·5 months). Three-year overall survival (OS) rates were similar between ESA/non-ESA in each arm. Patients receiving RBC transfusions had significantly shorter OS (P < 0·0001) versus non-RBC-transfusion patients. In conclusion, bortezomib did not add to melphalan haematological toxicity. Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS, or increase thromboembolic risk. However, RBC transfusion was associated with significantly shorter survival.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Disease-Free Survival; Erythrocyte Transfusion; Female; Hematinics; Humans; Incidence; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Pyrazines; Survival Rate; Thromboembolism

To describe histopathologic observations in eyes enucleated after intra-arterial chemotherapy (IAC) for retinoblastoma (Rb).. Retrospective histopathologic analysis of 8 eyes.. The eyes were enucleated for tumor viability (n = 4), neovascular glaucoma (n = 2), anaphylactic reaction from IAC (n = 1), and persistent retinal detachment with poor visualization of the tumor (n = 1). Of the 2 eyes judged clinically with complete tumor regression and the 5 with viable tumor, the findings were confirmed on histopathology. The Rb response ranged from minimal (n = 1) to moderate (n = 1) to extensive (n = 4) to complete regression (n = 2). Viable vitreous seeds (n = 4 eyes), invasion into the optic nerve (n = 3), reaching the lamina cribrosa in 2 cases, and invasion into the choroid (n = 1) were observed. Histopathologic evidence of ischemic atrophy involving the outer retina and choroid was found in 4 eyes. One eye treated at another center with IAC and enucleated by our team for recurrence was observed to have extensive choroidal and outer retinal atrophy. This case showed orbital vascular occlusion and subendothelial smooth muscle hyperplasia. Intravascular birefringent foreign material was observed in 5 cases within occluded vessels, stimulating a granulomatous inflammatory response. The foreign material comprised cellulose fibers (n = 3), synthetic fabric fibers (n = 1), or unknown composition (n = 2). Thrombosed blood vessels were identified in 5 eyes and involved ciliary arteries in the retrobulbar orbit (n = 5), scleral emissarial canals (n = 1), small choroidal vessels (n = 1), and central retinal artery (n = 1).. Retinoblastoma can be controlled with IAC, but histopathology of enucleated eyes reveals that ocular complications including thromboembolic events can occur.

Topics: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Child; Child, Preschool; Choroid Neoplasms; Eye Diseases; Eye Enucleation; Female; Fluorescein Angiography; Fluoroscopy; Humans; Infant; Injections, Intra-Arterial; Male; Melphalan; Neoplasm Invasiveness; Neoplasm Seeding; Ophthalmic Artery; Optic Nerve Neoplasms; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Thromboembolism; Vitreous Body

Thalidomide has received approval from the European Agency for the Evaluation of Medicinal Products for the treatment of newly diagnosed multiple myeloma (MM) patients older than 65 years or ineligible for transplant. The results of five phase III trials assessing thalidomide in combination with melphalan and prednisone (MPT) have demonstrated significantly improved response rates compared with melphalan and prednisone (MP) alone. Additionally, two of these studies showed that survival was extended by approximately 18 months in patients treated with MPT compared with MP alone. Thalidomide, in combination with MP, is associated with adverse events (AEs) including peripheral neuropathy and venous thromboembolism. In order to optimize the efficacy of MPT, a good awareness of these AEs is imperative. This manuscript outlines both evidence- and consensus-based recommendations discussed by a panel of experts, to provide a practical guide for physicians addressing the effective management of newly diagnosed, transplant-ineligible MM patients receiving thalidomide therapy.

Topics: Aged; Consensus; Europe; Guidelines as Topic; Humans; Melphalan; Multiple Myeloma; Prednisone; Risk Factors; Survival Rate; Thalidomide; Thromboembolism

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Enoxaparin; Humans; Lenalidomide; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Recurrence; Risk; Thalidomide; Thromboembolism; Time Factors