Characterization of haematological parameters with bortezomib–melphalan–prednisone versus melphalan–prednisone in newly diagnosed myeloma, with evaluation of long‐term outcomes and risk of thromboembolic events with use of erythropoiesis‐stimulating agents: analysis of the VISTA trial

Abstract

SummaryAlthough 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 Ò 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: 1AE03 (95% confidence interval 0AE76-1AE39); P = 0AE8478] in both arms (VMP: 19AE9/not reached; MP: 15AE0/17AE5 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 < 0AE0001) versus non-RBCtransfusion 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.

European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications

“…However, one randomized study (VISTA sub-analysis) showed no evidence of inferior outcome after ESA treatment, albeit patient numbers were very limited and, therefore, statistically under-powered. 43 The most recent guidelines from the American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO) recommend the administration of ESAs at the lowest possible dose to avoid transfusions. In case of iron deficiency, which is indicated by low transferrin satu-…”

Erythropoietin treatment in murine multiple myeloma: immune gain and bone loss

“…Moreover, the combined use of IMIDS with EPO might increase the risk of VTE 66 . On the other hand, it should be emphasized that proteasome inhibitors have been shown to be safe, even when combined with ESAs, as shown in the VISTA trial 21 .…”

“…We 6 7 11 17 and others 18 19 , have noted prolonged survival and improved immunological functions in MM mouse models and MM patients, linked to EPO administration. Notably, others reported contradicting data regarding rHuEPO treatment in MM patients 20 21 , which warrants further research to elucidate this question.…”

Myelosuppression, Bone Disease, and Acute Renal Failure: Evidence-Based Recommendations for Oncologic Emergencies

“…A few randomized studies have evaluated the impact of ESAs on outcomes in patients with MM. One randomized study showed no evidence of inferior outcome following ESA treatment; however, the trial was small and statistically underpowered (Richardson et al, 2011). ɐ To minimize the risk of infection, the use of neutropenic precautions is recommended in patients with MM (see Figure 3).…”