title: The possible role of burden of therapy on the risk of myeloma extramedullary spread.
abstract: Extramedullary relapse (EMR) represents a poor prognostic marker in the course of multiple myeloma (MM). We reviewed data from 329 patients, diagnosed between 2000 and 2010, without extramedullary disease at onset to explore possible risk factors for EMR. The median overall survival of our study cohort was 6.4 years. The risk of EMR was 28 % with a median time from diagnosis to first EMR of 2.2 years (0.2-9.1 years). Patients with soft tissue masses located in extra-osseous organs (EMR-S) showed the worst outcome, compared to those with tumor masses arising from adjacent bone (EMR-B) (median OS 1.6 vs 2.4 years, p = 0.006). In addition, patients with EMR-S showed a significant trend for further development of extramedullary masses in a very short time (3.7 vs 5.7 months for EMR-B, p = 0.043). Multivariate analysis failed to identify any clinically presenting features predictive for EMR. The occurrence of EMR was higher in patients with more complex treatment history, defined on the basis of longer treatment duration (≥6 vs <6 months) and on elevated number of treatment lines administered (>2 vs ≤2 lines) (HR = 4.5, p < 0.001 and HR = 9.0, p < 0.001, respectively, when one or both factors are present).In conclusion, increasing burden of treatment might be a possible risk factor for EMR. MM patients with multiple relapses should be comprehensively investigated including, when possible, a whole-body-targeted radiologic technique to accurately detect EMR. Treatment choice should take into account the very poor outcome for patients with soft tissue involvement.
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy. silvia_mangiacavalli@hotmail.com.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0001-9787-3083
authors.initials: S
authors.lastname: Mangiacavalli
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pompa
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ferretti
authors.affiliation: Service of Biometry and Statistics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Klersy
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cocito
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Varettoni
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: C S
authors.initials: CS
authors.lastname: Cartia
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069286:Bortezomib / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D023981:Sarcoma, Myeloid / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide
keywords: Extramedullary; Myeloma; Novel agents; Relapse