Orio, A. (Albert)

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    High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience
    (John Wiley & Sons Ltd, 2024) Gonzalez-Calle, V. (Veronica); Rodriguez-Otero, P. (Paula); Calasanz-Abinzano, M.J. (Maria Jose); Guijarro, M. (Manuela); Martínez-López, J. (Joaquín); Rosiñol, L. (Laura); Hernandez, M.T. (Miguel Teodoro); Teruel, A.I. (Ana Isabel); Gironella, M. (Mercedes); Orio, A. (Albert); Rubia, J. (Javier) de la; González-Rodriguez, A.P. (Ana Pilar); Bargay, J. (Joan); Arriba, F. (Felipe) de; Palomera, L. (Luis); González, M.S. (Marta Sonia); Sureda-Balari, A. M. (Anna Maria); Ocio, E.M. (Enrique M.); Lahuerta, J.J. (Juan José); Bladé, J. (Joan); San-Miguel, J.F. (Jesús F.); Mateos, M.V. (María Victoria); Gutierrez, N.C. (Norma C.)
    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.