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    Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Category: Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Prognostic subgroups in hyperdiploid myeloma and the role of modern treatments

    (PA-407) Prognostic Subgroups in Hyperdiploid Myeloma and the Role of Modern Treatments

    Wednesday, September 17, 2025

    Introduction:      Chromosomal abnormalities are important prognostic factors in multiple myeloma (MM). A hyperdiploid karyotype is considered currently of standard risk and there are doubts whether more intensive treatment or transplantation is needed. Also, the clinical impact of chromosome number and of additional–structural–chromosomal aberrations assessed by conventional karyotype has not been clearly defined.

    Methods:   We retrospectively reviewed the clinical, laboratory and treatment data of 80 patients with hyperdiploid MM to assess the abnormalities frequently found by cytogenetic analysis and their relationship to prognosis, especially in the era of modern treatments.

    Results:   The median age was 58 (31-83) years, ISS stage was I,II,III in 21, 24 and 35 patients, while 30/68 had R-ISS III. 71 patients (89%) were treated with at least one of the novel agents (bortezomib, lenalidomide, daratumumab), 34(42.5%) underwent autologous transplantation (ASCT), one allo-SCT and 2 received CAR-T cells. All patients had cytogenetic and 52/80 FISH analysis. Twenty patients had 47-50 chromosomes and 60 had >50 ( >65 in 7). Most patients (74, 92.5%) had both numerical and structural abnormalities. Thirty-one had < 3, 34 had 3-5 and 15 had ≥6 structural abnormalities. Chromosome 13 deletion was common (33 patients, 41.5%) as were abnormalities of chromosome 1 (40%) and t(11;14)(q13;q32) was observed in 6 patients. No high-risk abnormality involving 14q32 was found by karyotype or FISH. Patients with less structural abnormalities (0-2) tended to be younger and have less stage III disease (28% vs 48%, p=0.058). By univariate analysis, there was a trend for a worse outcome with increasing number of structural abnormalities, median OS 122, 91 and 28 months, 5year OS probability of 79.2%, 57% and 23% for < 3, 3-5 and ≥6 structural abnormalities respectively, p=0.071. No significant difference in survival was found by chromosome number. However a group of patients with high hyperdiploidy (51-65 chromosomes) and < 5 structural abnormalities showed a better outcome than the rest: median OS 91 vs 29 months, 5year OS 67% vs 32.3%, p=0.053. Yet, this group had inferior survival when compared to 60 patients with a normal karyotype (5year OS 67% vs 81%, p=0.003). This difference in survival was eliminated when only patients who received daratumumab in the first 2 lines were considered (p=0.67). Patients aged ≤ 67years had a longer survival with ASCT: medOS 133 vs 64 months, 5year OS 83% vs 53.6%, p=0.001. In multivariate analysis, significant factors were ASCT, age and a trend for -13/del13q.

    Conclusions:   

    Ιn conclusion, the conventional karyotype can evaluate hyperploidy, which affects a significant percentage of MM patients, and define subgroups with different prognosis, such as high hyperdiploidy with < 5 structural abnormalities. ASCT is beneficial for hyperpdiploid MM. Newer treatments, such as anti-CD33 antibody, improve the prognosis of this group even further, becoming similar to that of normal karyotype.