title: Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years.
abstract: Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease.
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany monika.engelhardt@uniklinik-freiburg.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Center of Clinical Trials, University Medical Center Freiburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ihorst
authors.affiliation: Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Milena
authors.initials: M
authors.lastname: Pantic
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Reinhardt
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waldschmidt
authors.affiliation: Pathology Department, University of Freiburg, Germany.
authors.forename: Annette M
authors.initials: AM
authors.lastname: May
authors.affiliation: Department of Medical Biometry and Statistics (IMBI), University of Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schumacher
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kleber
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D012042:Registries; D012306:Risk; D018426:SEER Program