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. 2024 Dec 10;8(12):e70031.
doi: 10.1002/hem3.70031. eCollection 2024 Dec.

High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience

Veronica González-Calle  1 , Paula Rodriguez-Otero  2 , Maria J Calasanz  2 , Manuela Guijarro  3 , Joaquin Martínez-López  3 , Laura Rosiñol  4 , Miguel T Hernández  5 , Ana I Teruel  6 , Mercedes Gironella  7 , Albert Oriol  8 , Javier de la Rubia  9 , Ana P González-Rodríguez  10 , Joan Bargay  11 , Felipe de Arriba  12 , Luis Palomera  13 , Marta-Sonia González-Pérez  14 , Anna Sureda  15 , Enrique Ocio  16 , Juan J Lahuerta  3 , Joan Bladé  4 , Jesus F San Miguel  2 , Maria V Mateos  1 , Norma C Gutiérrez  1
Affiliations

High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience

Veronica González-Calle et al. Hemasphere. .

Abstract

This study examines the impact of cytogenetic abnormalities and their co-segregation on the prognosis of newly diagnosed multiple myeloma patients. The analysis included 1304 patients from four different GEM-PETHEMA clinical trials. Genetic alterations, such as t(4;14), t(14;16), del(17p), +1q, and del(1p), were investigated using FISH on CD38 purified plasma cells. The frequency of genetic alterations detected were as follows: del(17p) in 8%, t(4;14) in 12%, t(14;16) in 3%, +1q in 43%, and del(1p) in 8%. The median follow-up was 61 months, and the median progression-free survival (PFS) and overall survival (OS) were 44 months and not reached, respectively. Consistent with previous reports, the presence of t(4;14) was associated with shorter PFS and OS. In our series, the presence of t(14;16) did not impact survival, maybe due to limitations in sample size. Del(17p) was linked to poor prognosis using a cut-off level of ≥20% positive cells, without any impact of higher cut-off in prognosis, except for patients with clonal fraction ≥80% who had a dismal outcome. Cosegregation of cytogenetic abnormalities patients worsened the prognosis in t(4;14) patients but not in patients with del(17p), which retained its adverse prognosis even as a solitary abnormality. Gain(1q) was associated with significantly shorter PFS and OS, while del(1p) affected PFS but not OS. Nevertheless, when co-segregation was eliminated, the detrimental effect of +1q or del(1p) was no longer observed. In conclusion, this study confirms the prognostic significance of high-risk cytogenetic abnormalities in MM and highlights the importance of considering co-occurrence for accurate prognosis assessment.

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Conflict of interest statement

Veronica González‐Calle: Consulting or Advisory Role: Janssen. Speakers' Bureau: Janssen, GlaxoSmithKline, Pfizer, Bristol Myers Squibb/Celgene. Travel, Accommodations, Expenses: Janssen, GlaxoSmithKline. Paula Rodriguez‐Otero declares honoraria derived from Consulting or advisory board role: Celgene‐BMS, Janssen, Roche, Abbvie, Pfizer, GSK, Sanofi, H3Biomedicine. Steering committee member: Celgene‐BMS, Regeneron, Janssen Speaker's bureau: Janssen, Celgene‐BMS, GSK, Sanofi, Abbvie. Travel grant: Pfizer, and is an Editor of HemaSphere. Miguel T. Hernández: Consulting or Advisory Role: Janssen, Sanofi/Aventis, Celgene/Bristol Myers Squibb, GlaxoSmithKline. Speakers' Bureau: Janssen, Celgene/Bristol Myers Squibb, GlaxoSmithKline. Research Funding: Celgene/Bristol Myers Squibb (Inst). Laura Rosiñol reports honoraria from Janssen, Celgene, Amgen, and Takeda. Joaquin Martínez‐López declares honoraria from consulting activities from Astellas Pharma, BMS, F. Hoffman‐La Roche, Janssen, Novartis, Sanofi. Research grant from BMS. Ana P. González‐Rodríguez reports honoraria from Janssen, Celgene, Takeda, and Amgen. JdlR is a consultant for Bristol‐Meyers Squibb, GlaxoSmithKline, Janssen, Menarini, Pfizer, Sanofi, and Takeda and is on the advisory board of GlaxoSmithKline, Janssen, Pfizer, and Sanofi. Maria V. Mateos: declares honoraria derived from lectures and advisory roles at Amgen, Celgene, BMS, GSK, Janssen, Pfizer, Regeneron, Sanofi, and Takeda. Anna Sureda reports consultancy for BMS, Celgene, Gilead, Janssen, MSD, Novartis, Sanofi, Takeda, and GSK; speakers bureau for Takeda; travel grants from BMS, Celgene, Janssen, Roche, Sanofi, and Takeda; research support from Takeda and BMS. Albert Oriol declares consultant activities from Amgen, Celgene, BMS, GSK, Janssen, and Sanofi. EMO reports consulting or an advisory role for Amgen, AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Karyopharm, Menarini‐Stemline, Mundipharma, Oncopeptides, Sanofi, Secura Bio, and Takeda; meeting and/or travel expenses from Bristol Myers Squibb, GlaxoSmithKline, Janssen, Lilly, and Sanofi; and honoraria from Amgen, Asofarma, Bristol Myers Squibb, GlaxoSmithKline, Janssen, MSD, Pfizer, Sanofi, and Takeda. Joan Bargay: honoraria for lectures and advisory boards from Janssen, BMS‐Celgene, Amgen, Takeda, Oncopeptides. Juan J. Lahuerta: Consulting or Advisory Role: Celgene, Amgen, Janssen‐Cilag, Sanofi. Travel, Accommodations, Expenses: Celgene, Pfizer. Jesus F. San Miguel declares consulting activities from Abbvie, Amgen, BMS, Celgene, F. Hoffman‐La Roche, GSK, HaemaLogiX, KaryoPharm, Merck, Novartis, Pfizer, Regeneron, Sanofi‐Aventis, Takeda, and SecuraBio. Maria V. Mateos: honoraria for lectures and advisory boards from Janssen, Celgene, Takeda, Amgen, GSK, Abbvie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides; The remaining authors declare no competing interests relative to this work.

Figures

Figure 1
Figure 1
Survival curves by status of t(4;14). (A) Progression‐free survival (PFS) by overall presence or absence of t(4;14). (B) PFS in patients with t(4;14) alone or with other hits. (C) Overall survival by t(4;14). (D) Overall survival in patients with t(4;14) alone or with other hits. mPFS, median progression‐free survival; mOS, median overall survival; OS, overall survival.
Figure 2
Figure 2
Survival curves by status of del(17p). (A) Progression‐free survival (PFS) by overall presence or absence of del(17p). (B) PFS in patients with del(17p) as a single cytogenetic abnormality. (C) Overall survival (OS) by del(17p). (D) OS in patients with del(17p) as a single cytogenetic abnormality. NS, nonsignificant.
Figure 3
Figure 3
Survival curves by status of gain(1q). (A) Progression‐free survival by overall presence or absence of gain(1q). (B) Progression‐free survival in patients with gain(1q) as a single cytogenetic abnormality. (C) Overall survival by gain(1q). (D) Overall survival in patients with gain(1q) as a single cytogenetic abnormality.
Figure 4
Figure 4
Survival curves by status of del(1p). (A) Progression‐free survival by overall presence or absence of del(1p). (B) Progression‐free survival in patients with del(1p) as a single cytogenetic abnormality. (C) Overall survival by del(1p). (D) Overall survival in patients with del(1p) as a single cytogenetic abnormality.
Figure 5
Figure 5
Survival curves by R‐ISS. (A) Pogression‐free survival by R‐ISS. (B) Progression‐free survival by R‐ISS in four categories considering group II split into two subgroups according to the absence or presence of high‐risk cytogenetic abnormalities (IIa and IIb, respectively). (C) Overall survival R‐ISS. (D) Overall survival by R‐ISS in four categories considering group II split into two subgroups according to the absence or presence of high‐risk cytogenetic abnormalities (IIa and IIb, respectively).
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References

    1. Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012;12(5):335‐348. - PubMed
    1. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122‐1128. - PMC - PubMed
    1. Shah UA, Mailankody S. Emerging immunotherapies in multiple myeloma. BMJ [Internet]. 2020;370:m3176. 10.1136/bmj.m3176 - DOI - PubMed
    1. Cardona‐Benavides IJ, de Ramón C, Gutiérrez NC. Genetic abnormalities in multiple myeloma: prognostic and therapeutic implications. Cells. 2021;10(2):336. - PMC - PubMed
    1. Ross FM, Avet‐Loiseau H, Ameye G, et al. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica. 2012;97(8):1272‐1277. - PMC - PubMed

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