Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma

Author:

Mellors Patrick W.1ORCID,Binder Moritz2ORCID,Ketterling Rhett P.3,Greipp Patricia T.3,Baughn Linda B.3,Peterson Jess F.3,Jevremovic Dragan3,Pearce Kathryn E.3,Buadi Francis K.2,Lacy Martha Q.2ORCID,Gertz Morie A.2,Dispenzieri Angela2ORCID,Hayman Suzanne R.2,Kapoor Prashant2,Gonsalves Wilson I.2,Hwa Yi L.2,Fonder Amie2,Hobbs Miriam2,Kourelis Taxiarchis2,Warsame Rahma2,Lust John A.2,Leung Nelson2ORCID,Go Ronald S.2,Kyle Robert A.2,Rajkumar S. Vincent2ORCID,Kumar Shaji K.2ORCID

Affiliation:

1. Department of Internal Medicine,

2. Division of Hematology, and

3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

Abstract

AbstractMetaphase cytogenetic abnormalities, plasma cell proliferation index (PCPro), and gain 1q by fluorescence in situ hybridization (FISH) are associated with inferior survival in newly diagnosed multiple myeloma (MM) treated with novel agents; however, their role in risk stratification is unclear in the era of the revised International Staging System (R-ISS). The objective of this study was to determine if these predictors improve risk stratification in newly diagnosed MM when accounting for R-ISS and age. We studied a retrospective cohort of 483 patients with newly diagnosed MM treated with proteasome inhibitors and/or immunomodulators. On multivariable analysis, R-ISS, age, metaphase cytogenetic abnormalities (both in aggregate and for specific abnormalities), PCPro, and FISH gain 1q were associated with inferior progression-free (PFS) and overall survival (OS). We devised a risk scoring system based on hazard ratios from multivariable analyses and assigned patients to low-, intermediate-, and high-risk groups based on their cumulative scores. The addition of metaphase cytogenetic abnormalities, PCPro, and FISH gain 1q to a risk scoring system accounting for R-ISS and age did not improve risk discrimination of Kaplan-Meier estimates for PFS or OS. Moreover, they did not improve prognostic performance when evaluated by Uno’s censoring-adjusted C-statistic. Lastly, we performed a paired analysis of metaphase cytogenetic and interphase FISH abnormalities, which revealed the former to be insensitive for the detection of prognostic chromosomal abnormalities. Ultimately, metaphase cytogenetics lack sensitivity for important chromosomal aberrations and, along with PCPro and FISH gain 1q, do not improve risk stratification in MM when accounting for R-ISS and age.

Publisher

American Society of Hematology

Subject

Hematology

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