INTRODUCTION: The clinical application of the Revised International Staging System (R-ISS) for multiple myeloma may be limited by heterogeneity in clinical interphase fluorescent in situ hybridization (FISH) practices for detecting chromosomal abnormalities (CAs). Next generation sequencing (NGS)-based FISH (Seq-FISH) has demonstrated improved sensitivity and similar specificity relative to clinical FISH, and provides a standardized, single-pass method for identifying high-risk CAs. To date, calculating R-ISS stage using Seq-FISH (R-ISS-NGS) has not been validated. PATIENTS AND METHODS: We identified 672 patients with sufficient data to calculate R-ISS-NGS from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study. R-ISS-NGS was calculated from original ISS stage, lactate dehydrogenase, and CAs detected by Seq-FISH. Endpoints included overall survival and progression-free survival. We conducted multivariate analyses controlling for age and gender in order to compare outcomes across stages I to III of both the original ISS and R-ISS-NGS. RESULTS: The median follow-up was 24 months. The R-ISS-NGS resulted in significant redistribution of patients into stage II, relative to the original ISS. With respect to stage I, R-ISS-NGS stages II and III of were associated with worse progression-free survival or overall survival, more so than the staging schema of the ISS, thus validating the use of Seq-FISH in staging. CONCLUSION: Using CAs detected by Seq-FISH and data from the CoMMpass study, we validated the R-ISS with a large, generalizable cohort. This study validates the substitution of Seq-FISH for clinical FISH, especially in large registry studies. Additionally, use of the validated R-ISS-NGS will strengthen outcomes research generated from the CoMMpass study.
INTRODUCTION: The clinical application of the Revised International Staging System (R-ISS) for multiple myeloma may be limited by heterogeneity in clinical interphase fluorescent in situ hybridization (FISH) practices for detecting chromosomal abnormalities (CAs). Next generation sequencing (NGS)-based FISH (Seq-FISH) has demonstrated improved sensitivity and similar specificity relative to clinical FISH, and provides a standardized, single-pass method for identifying high-risk CAs. To date, calculating R-ISS stage using Seq-FISH (R-ISS-NGS) has not been validated. PATIENTS AND METHODS: We identified 672 patients with sufficient data to calculate R-ISS-NGS from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study. R-ISS-NGS was calculated from original ISS stage, lactate dehydrogenase, and CAs detected by Seq-FISH. Endpoints included overall survival and progression-free survival. We conducted multivariate analyses controlling for age and gender in order to compare outcomes across stages I to III of both the original ISS and R-ISS-NGS. RESULTS: The median follow-up was 24 months. The R-ISS-NGS resulted in significant redistribution of patients into stage II, relative to the original ISS. With respect to stage I, R-ISS-NGS stages II and III of were associated with worse progression-free survival or overall survival, more so than the staging schema of the ISS, thus validating the use of Seq-FISH in staging. CONCLUSION: Using CAs detected by Seq-FISH and data from the CoMMpass study, we validated the R-ISS with a large, generalizable cohort. This study validates the substitution of Seq-FISH for clinical FISH, especially in large registry studies. Additionally, use of the validated R-ISS-NGS will strengthen outcomes research generated from the CoMMpass study.
Authors: Rowan Kuiper; Sonja Zweegman; Mark van Duin; Martin H van Vliet; Erik H van Beers; Belinda Dumee; Michael Vermeulen; Jasper Koenders; Bronno van der Holt; Heleen Visser-Wisselaar; Markus Hansson; Annette W G van der Velden; H Berna Beverloo; Marian Stevens-Kroef; Mark-David Levin; Annemiek Broijl; Anders Waage; Pieter Sonneveld Journal: Blood Adv Date: 2020-12-22
Authors: James Smadbeck; Jess F Peterson; Kathryn E Pearce; Beth A Pitel; Andrea Lebron Figueroa; Michael Timm; Dragan Jevremovic; Min Shi; A Keith Stewart; Esteban Braggio; Daniel L Riggs; P Leif Bergsagel; George Vasmatzis; Hutton M Kearney; Nicole L Hoppman; Rhett P Ketterling; Shaji Kumar; S Vincent Rajkumar; Patricia T Greipp; Linda B Baughn Journal: Blood Cancer J Date: 2019-12-16 Impact factor: 11.037
Authors: Nadine H Abdallah; Moritz Binder; S Vincent Rajkumar; Patricia T Greipp; Prashant Kapoor; Angela Dispenzieri; Morie A Gertz; Linda B Baughn; Martha Q Lacy; Suzanne R Hayman; Francis K Buadi; David Dingli; Ronald S Go; Yi L Hwa; Amie L Fonder; Miriam A Hobbs; Yi Lin; Nelson Leung; Taxiarchis Kourelis; Rahma Warsame; Mustaqeem A Siddiqui; Robert A Kyle; P Leif Bergsagel; Rafael Fonseca; Rhett P Ketterling; Shaji K Kumar Journal: Blood Cancer J Date: 2022-01-31 Impact factor: 9.812