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. 2022 Jan 31;12(1):21.
doi: 10.1038/s41408-022-00611-x.

A simple additive staging system for newly diagnosed multiple myeloma

Nadine H Abdallah  1 , Moritz Binder  1 , S Vincent Rajkumar  1 , Patricia T Greipp  2 , Prashant Kapoor  1 , Angela Dispenzieri  1 , Morie A Gertz  1 , Linda B Baughn  2 , Martha Q Lacy  1 , Suzanne R Hayman  1 , Francis K Buadi  1 , David Dingli  1 , Ronald S Go  1 , Yi L Hwa  1 , Amie L Fonder  1 , Miriam A Hobbs  1 , Yi Lin  1 , Nelson Leung  1   3 , Taxiarchis Kourelis  1 , Rahma Warsame  1 , Mustaqeem A Siddiqui  1 , Robert A Kyle  1 , P Leif Bergsagel  4 , Rafael Fonseca  4 , Rhett P Ketterling  1 , Shaji K Kumar  5
Affiliations

A simple additive staging system for newly diagnosed multiple myeloma

Nadine H Abdallah et al. Blood Cancer J. .

Abstract

Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2-12.6), 7.0 (95% CI: 6.3-9.2), and 4.5 (95% CI: 3.7-5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P < 0.001). This 5-factor, 3-tier system is easy to implement in practice and improves upon the current R-ISS.

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Conflict of interest statement

PK received research funding from Takeda Pharmaceuticals, Celgene, and Amgen. AD received research funding from Celgene, Millennium Pharmaceuticals, Pfizer, and Janssen and received a travel grant from Pfizer. MAG served as a consultant for Millennium Pharmaceuticals and received honoraria from Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Prothena, Ionis Pharmaceuticals, and Amgen. MQL received research funding from Celgene. NL serves on an advisory board for Takeda Pharmaceuticals. RF served as a consultant for Amgen, BMS, Celgene, Takeda, Bayer, Janssen, Novartis, Pharmacyclics, Sanofi, Karyopharm, Merck, Juno, Kite, Aduro, OncoTracker, Oncopeptides, GSK, and AbbVie, and is on the scientific Advisory Board for Adaptive Biotechnologies, Caris Life Sciences and OncoTracker. SKK served as a consultant for Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Janssen, and Bristol-Myers Squibb and received research funding from Celgene, Millennium Pharmaceuticals, Novartis, Onyx Pharmaceuticals, AbbVie, Janssen, and Bristol-Myers Squibb. The remaining authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. PFS and OS based on the updated R-ISS.
a PFS (months) and b OS (years) in MM patients with stage I (red curve), II (green), and III (blue curve) based on the updated R-ISS. MM multiple myeloma, OS overall survival, PFS progression-free survival, R-ISS revised international staging system. The P values for each pair of groups are presented between the corresponding curves.
Fig. 2
Fig. 2. PFS and OS based on the MASS using the Mayo Clinic cohort.
a PFS (months) and b OS (years) in MM patients with no HR factors (stage I) (red curve), 1 HR factor (stage II) (green curve), and ≥2 HR factors (stage III) (blue curve). HR factors are defined as any of: HR IgH translocations, 1q gain/amplification, chromosome 17 abnormality [(del)17p/monosomy 17], ISS stage III, and LDH > ULN. del: deletion, HR: high-risk, IgH immunoglobulin heavy chain gene locus, ISS international staging system, LDH lactate dehydrogenase, MASS Mayo Additive Staging System, MM multiple myeloma, OS overall survival, PFS progression-free survival, ULN upper limit of normal. The P values for each pair of groups are presented between the corresponding curves.
Fig. 3
Fig. 3. OS based on the MASS by age.
OS (years) in MM patients with MASS I (red curve), MASS II (green curve), and MASS III (blue curve) who are a <65 and b ≥65 years of age. MASS Mayo Additive Staging System, MM multiple myeloma, OS overall survival. The P values for each pair of groups are presented between the corresponding curves.
Fig. 4
Fig. 4. OS based on the MASS by transplant status.
OS (years) in MM patients with MASS I (red curve), MASS II (green curve), and MASS III (blue curve) who (a) did not undergo transplant and in those who (b) underwent transplant. MASS Mayo Additive Staging System, MM multiple myeloma, OS overall survival. The P values for each pair of groups are presented between the corresponding curves.
Fig. 5
Fig. 5. Stage migration between R-ISS and MASS and ISS and MASS.
The distribution and migration of patients between disease stages using ISS, R-ISS, and MASS risk stratification systems. ISS International Staging System, R-ISS Revised International Staging System, MASS Mayo Additive Staging System.
Fig. 6
Fig. 6. PFS and OS based on the MASS using the MMRF cohort.
a PFS (months) and b OS (years) in MM patients with MASS I (red curve), MASS II (green curve), and MASS III (blue curve) using the MMRF cohort. MASS Mayo Additive Staging System, MM multiple myeloma, OS overall survival, PFS progression-free survival. The P values for each pair of groups are presented between the corresponding curves.
See this image and copyright information in PMC

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