PMID- 32469686 OWN - NLM STAT- MEDLINE DCOM- 20210614 LR - 20211022 IS - 2688-1535 (Electronic) IS - 2688-1527 (Print) IS - 2688-1527 (Linking) VI - 16 IP - 10 DP - 2020 Oct TI - Variability in Cytogenetic Testing for Multiple Myeloma: A Comprehensive Analysis From Across the United States. PG - e1169-e1180 LID - 10.1200/JOP.19.00639 [doi] AB - PURPOSE: Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized. METHODS: We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide. RESULTS: Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13-related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%). CONCLUSIONS: We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches. FAU - Yu, Yang AU - Yu Y AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Brown Wade, Niquelle AU - Brown Wade N AUID- ORCID: 0000-0001-7405-8772 AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Hwang, Amie E AU - Hwang AE AUID- ORCID: 0000-0002-5538-131X AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Nooka, Ajay K AU - Nooka AK AUID- ORCID: 0000-0003-4165-6869 AD - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. FAU - Fiala, Mark A AU - Fiala MA AUID- ORCID: 0000-0002-0208-5023 AD - Division of Oncology, Washington University School of Medicine, Saint Louis, MO. FAU - Mohrbacher, Ann AU - Mohrbacher A AD - Department of Medicine, Division of Hematology, University of Southern California, Los Angeles, CA. FAU - Peters, Edward S AU - Peters ES AD - Louisiana State University School of Public Health, New Orleans, LA. FAU - Pawlish, Karen AU - Pawlish K AD - New Jersey Department of Health, Trenton, NJ. FAU - Bock, Cathryn AU - Bock C AD - Karmanos Cancer Center, Wayne State University, Detroit, MI. FAU - Van Den Berg, David J AU - Van Den Berg DJ AUID- ORCID: 0000-0002-5404-5218 AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Rand, Kristin A AU - Rand KA AD - Ancestry.com, San Francisco, CA. FAU - Stram, Daniel AU - Stram D AD - Ancestry.com, San Francisco, CA. FAU - Conti, David V AU - Conti DV AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Auclair, Daniel AU - Auclair D AUID- ORCID: 0000-0001-5151-3058 AD - Multiple Myeloma Research Foundation, Norwalk, CT. FAU - Colditz, Graham A AU - Colditz GA AD - Division of Oncology, Washington University School of Medicine, Saint Louis, MO. FAU - Mehta, Jayesh AU - Mehta J AD - Feinberg School of Medicine, Northwestern University, Chicago, IL. FAU - Haiman, Christopher A AU - Haiman CA AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Terebelo, Howard AU - Terebelo H AD - Providence Hospital, Southfield, MI. FAU - Janakiraman, Nalini AU - Janakiraman N AD - Division of Hematology-Oncology, Henry Ford Hospital, Detroit, MI. FAU - Singhal, Seema AU - Singhal S AD - Feinberg School of Medicine, Northwestern University, Chicago, IL. FAU - Chiu, Brian AU - Chiu B AD - Department of Public Health Sciences, University of Chicago, Chicago, IL. FAU - Vij, Ravi AU - Vij R AUID- ORCID: 0000-0001-8795-3610 AD - Division of Oncology, Washington University School of Medicine, Saint Louis, MO. FAU - Bernal-Mizrachi, Leon AU - Bernal-Mizrachi L AD - Grady Memorial Hospital, Emory University, Atlanta, GA. FAU - Zonder, Jeffrey A AU - Zonder JA AUID- ORCID: 0000-0002-1741-2795 AD - Karmanos Cancer Center, Wayne State University, Detroit, MI. FAU - Huff, Carol A AU - Huff CA AUID- ORCID: 0000-0003-0545-0708 AD - Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. FAU - Lonial, Sagar AU - Lonial S AD - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. FAU - Orlowski, Robert Z AU - Orlowski RZ AD - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Cozen, Wendy AU - Cozen W AUID- ORCID: 0000-0003-3415-8247 AD - Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. AD - Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. FAU - Ailawadhi, Sikander AU - Ailawadhi S AUID- ORCID: 0000-0002-8377-8111 AD - Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL. LA - eng GR - P50 CA186781/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20200529 PL - United States TA - JCO Oncol Pract JT - JCO oncology practice JID - 101758685 SB - IM CIN - 10.1200/JOP.19.00309 MH - Cytogenetic Analysis/*standards MH - Humans MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - *Multiple Myeloma/diagnosis/genetics MH - United States PMC - PMC7564132 COIS- VARIABILITY IN CYTOGENETIC TESTING FOR MULTIPLE MYELOMA: A COMPREHENSIVE ANALYSIS FROM ACROSS THE UNITED STATES: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). NIQUELLE BROWN WADE: Employment: Cigna AJAY K. NOOKA: Consulting or Advisory Role: Amgen, Janssen Oncology, Celgene, Spectrum Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline, Takeda, Oncopeptides, Karyopharm Therapeutics Research Funding: Amgen (Inst), Janssen Oncology (Inst), Takeda (Inst) Travel, Accommodations, Expenses: GSK DANIEL STRAM: Employment: Personalis (I) GRAHAM A. COLDITZ: Consulting or Advisory Role: Grail Patents, Royalties, Other Intellectual Property: Royalties as author for UptoDate JAYESH MEHTA: Honoraria: Celgene, Celgene (I), Takeda, Takeda (I), BMS, BMS (I), Janssen, Janssen (I) Speakers' Bureau: Celgene, Celgene (I), Takeda, Takeda (I), BMS, BMS (I), Janssen, Janssen (I) HOWARD TEREBELO: Consulting or Advisory Role: Celgene Speakers' Bureau: Janssen Oncology SEEMA SINGHAL: Honoraria: Celgene, Celgene (I), Takeda, Takeda (I), BMS, BMS (I), Janssen, Janssen (I) Honoraria: Celgene, Celgene (I), Takeda, Takeda (I), BMS, BMS (I), Janssen, Janssen (I) RAVI VIJ: Consulting or Advisory Role: Bristol-Myers Squibb, Celgene, Janssen, Sanofi, Karyopharm Therapeutics, Jazz Pharmaceuticals, Amgen, Takeda, AbbVie Research Funding: Amgen, Takeda, Celgene, Bristol-Myers Squibb Travel, Accommodations, Expenses: Celgene, Bristol-Myers Squibb, Sanofi, Janssen, DAVAOncology, Karyopharm Therapeutics, Amgen, Takeda, AbbVie LEON BERNAL-MIZRACHI: Employment: Winship Cancer Institute, Kodikas Therapeutic Solutions, Takeda Science Foundation Stock and Other Ownership Interests: Kodikas Therapeutic Solutions Honoraria: Celgene Consulting or Advisory Role: Celgene Research Funding: Takeda Patents, Royalties, Other Intellectual Property: We have discovered that translocation of NFKB2 predicts response to proteasome inhibitors. Test has been patented and licensed to Empire Genomics Travel, Accommodations, Expenses: Celgene JEFFREY A. ZONDER: Consulting or Advisory Role: Celgene, Bristol-Myers Squibb, Prothena, Janssen, Amgen, Takeda, Caelum, Intellia Therapeutics, Alnylam, Oncotherapeutics Research Funding: Celgene (Inst), BMS (Inst) CAROL A. HUFF: Consulting or Advisory Role: Karyopharm Therapeutics, Sanofi Genzyme, GlaxoSmithKline, miDiagnostics, Janssen Research Funding: Ichnos (Inst) SAGAR LONIAL: Consulting or Advisory Role: Celgene, Bristol-Myers Squibb, Janssen Oncology, Novartis, GlaxoSmithKline, Amgen, AbbVie, Takeda, Merck, Juno Therapeutics Research Funding: Celgene, Bristol-Myers Squibb, Takeda ROBERT Z. ORLOWSKI: Consulting or Advisory Role: Amgen, Celgene, Ionis Pharmaceuticals, Legend Biotech, Molecular Partners, Sanofi- Aventis, Servier, Takeda, Kite Pharma, Juno Therapeutics, GSK Biologicals, FORMA Therapeutics, Bristol-Myers Squibb, Janssen Biotech Research Funding: BioTheryX SIKANDER AILAWADHI: Consulting or Advisory Role: Amgen, Takeda, Celgene, Janssen Biotech Research Funding: Pharmacyclics (Inst), Janssen Biotech (Inst), Cellectar (Inst), Phosplatin Therapeutics (Inst), Celgene (Inst) Travel, Accommodations, Expenses: Amgen, Takeda, Novartis No other potential conflicts of interest were reported. EDAT- 2020/05/30 06:00 MHDA- 2021/06/16 06:00 PMCR- 2021/10/01 CRDT- 2020/05/30 06:00 PHST- 2020/05/30 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2020/05/30 06:00 [entrez] PHST- 2021/10/01 00:00 [pmc-release] AID - 1900639 [pii] AID - 10.1200/JOP.19.00639 [doi] PST - ppublish SO - JCO Oncol Pract. 2020 Oct;16(10):e1169-e1180. doi: 10.1200/JOP.19.00639. Epub 2020 May 29.