Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: A pooled analysis of two studies

Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with MM receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard-risk versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard-risk versus high-risk patients, we observed similar progression-free survival (PFS) (3-year PFS: 52% vs. 43%, respectively; P=0.50), overall survival (OS) (3-year OS: 78% vs. 73%; P=0.38), and overall response rate (88% vs. 95%; P=0.47), with no statistical differences between the two groups. No difference in terms of PFS was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed MM patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted in similar PFS and OS as in standard-risk patients

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: A pooled analysis of two studies

open20noFunding: The IST-CAR-561 (NCT01857115) study was sponsored by Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON, the Netherlands), in collaboration with Fondazione Neoplasie Sangue ONLUS (Italy). The IST-CAR-506 (NCT01346787) study was sponsored by the HOVON Foundation and co-sponsored by Fondazione Neoplasie Sangue ONLUS. Both trials were supported by funding from AMGEN (Onyx Pharmaceuticals), which had no role in study design, data collection, data analysis, data interpretation, writing of the report or publication of this article. The corresponding author had full access to all the data in the two studies, and had final responsibility for the decision to prepare and submit this manuscript for publication, together with the other authors.Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with MM receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard-risk versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard-risk versus high-risk patients, we observed similar progression-free survival (PFS) (3-year PFS: 52% vs. 43%, respectively; P=0.50), overall survival (OS) (3-year OS: 78% vs. 73%; P=0.38), and overall response rate (88% vs. 95%; P=0.47), with no statistical differences between the two groups. No difference in terms of PFS was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed MM patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted in similar PFS and OS as in standard-risk patients.noneMina R.; Bonello F.; Petrucci M.T.; Liberati A.M.; Conticello C.; Ballanti S.; Musto P.; Olivieri A.; Benevolo G.; Capra A.; Gilestro M.; Galieni P.; Cavo M.; Siniscalchi A.; Palumbo A.; Montefusco V.; Gaidano G.; Omede P.; Boccadoro M.; Bringhen S.Mina R.; Bonello F.; Petrucci M.T.; Liberati A.M.; Conticello C.; Ballanti S.; Musto P.; Olivieri A.; Benevolo G.; Capra A.; Gilestro M.; Galieni P.; Cavo M.; Siniscalchi A.; Palumbo A.; Montefusco V.; Gaidano G.; Omede P.; Boccadoro M.; Bringhen S