PMID- 32107329 OWN - NLM STAT- MEDLINE DCOM- 20210527 LR - 20210527 IS - 1592-8721 (Electronic) IS - 0390-6078 (Print) IS - 0390-6078 (Linking) VI - 106 IP - 4 DP - 2021 Apr 1 TI - Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies. PG - 1079-1085 LID - 10.3324/haematol.2019.243428 [doi] AB - Despite remarkable advances in the treatment of multiple myeloma 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 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 multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- 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- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (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 progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506). FAU - Mina, Roberto AU - Mina R AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Bonello, Francesca AU - Bonello F AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Petrucci, Maria Teresa AU - Petrucci MT AD - Hematology, Dept. of Cellular Biotechnologies and Hematology, Sapienza University of Rome, IT. FAU - Liberati, Anna Marina AU - Liberati AM AD - Universita degli Studi di Perugia,SCU Oncoematologia-Azienda Ospedaliera Santa Maria di Terni. FAU - Conticello, Concetta AU - Conticello C AD - Division of Hematology, AOU Policlinico-OVE, University of Catania, Catania, IT. FAU - Ballanti, Stelvio AU - Ballanti S AD - Reparto di Ematologia con TMO, Ospedale Santa Maria della Misericordia, Perugia, IT. FAU - Musto, Pellegrino AU - Musto P AD - IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), IT. FAU - Olivieri, Attilio AU - Olivieri A AD - Clinica di Ematologia, Universita Politecnica delle Marche, Ancona, IT. FAU - Benevolo, Giulia AU - Benevolo G AD - Hematology, Citta della Salute e della Scienza, Turin, IT. FAU - Capra, Andrea AU - Capra A AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Gilestro, Milena AU - Gilestro M AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Galieni, Piero AU - Galieni P AD - Division of Hematology, Ospedale "C. e G. Mazzoni", ASUR Marche-AV5, Ascoli Piceno, IT. FAU - Cavo, Michele AU - Cavo M AD - Istituto di Ematologia e Oncologia Medica Seragnoli. FAU - Siniscalchi, Agostina AU - Siniscalchi A AD - UOC Ematologia, Ospedale S. Eugenio, ASLRM2, Rome, IT. FAU - Palumbo, Antonio AU - Palumbo A AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Montefusco, Vittorio AU - Montefusco V AD - Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milano, IT. FAU - Gaidano, Gianluca AU - Gaidano G AD - Hematology, Department of Translational Medicine, Universita del Piemonte Orientale, Novara. FAU - Omede, Paola AU - Omede P AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Boccadoro, Mario AU - Boccadoro M AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. FAU - Bringhen, Sara AU - Bringhen S AD - Division of Hematology,University of Torino, AOU Citta della Salute e della Scienza di Torino. LA - eng SI - ClinicalTrials.gov/NCT01857115 SI - ClinicalTrials.gov/NCT01346787 PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20210401 PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (Oligopeptides) RN - 72X6E3J5AR (carfilzomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Cyclophosphamide/therapeutic use MH - Dexamethasone/therapeutic use MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Multiple Myeloma/diagnosis/drug therapy MH - Oligopeptides MH - Treatment Outcome PMC - PMC8018137 EDAT- 2020/02/29 06:00 MHDA- 2021/05/28 06:00 PMCR- 2020/02/27 CRDT- 2020/02/29 06:00 PHST- 2020/08/03 00:00 [received] PHST- 2020/02/29 06:00 [pubmed] PHST- 2021/05/28 06:00 [medline] PHST- 2020/02/29 06:00 [entrez] PHST- 2020/02/27 00:00 [pmc-release] AID - haematol.2019.243428 [pii] AID - 10.3324/haematol.2019.243428 [doi] PST - epublish SO - Haematologica. 2021 Apr 1;106(4):1079-1085. doi: 10.3324/haematol.2019.243428.