Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated with clinical heterogeneity and intermediate cytogenetic risk when found in isolation. The presence of gene mutations in this group of patients and the prognostic significance has not been extensively analyzed. Targeted deep sequencing was performed in a cohort of 79 MDS patients showing isolated +8. The most frequently mutated genes were: TET2 (38%), STAG2 (34.2%), SRSF2 (29.1%) and RUNX1 (26.6%). The mutational profile identified a high-risk subgroup with mutations in STAG2, SRSF2 and/or RUNX1, resulting in shorter time to acute myeloid leukemia progression (14 months while not reached in patients without these mutations, p < 0.0001) and shorter overall survival (23.7 vs. 46.3 months, p = 0.001). Multivariate analyses revealed the presence of mutations in these genes as an independent prognostic factor in MDS showing +8 isolated (HR: 3.1; p < 0.01). Moreover, 39.5% and 15.4% of patients classified as low/intermediate risk by the IPSS-R and IPSS-M, respectively, were re-stratified as a high-risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort (n = 2494). In summary, this study validates the prognosis significance of somatic mutations shown in IPSS-M and adds STAG2 as an important mutated gene to consider in this specific subgroup of patients. The mutational profile in isolated +8 MDS patients could, therefore, offer new insights for the correct management of patients with a higher risk of leukemic transformation.

Introduction Elranatamab is a bispecific anti-B-cell maturation antigen (BCMA) and -CD3 antibody recently approved in Spain for the treatment of adult patients with triple-class exposed relapsed and refractory multiple myeloma (TCE-RRMM). The objective of this analysis was to assess its cost-effectiveness versus teclistamab, another recently approved bispecific antibody, and a treatment basket representing current physician’s choice of treatment (PCT). Methods A partitioned survival model with three health states was adapted to the Spanish setting. Efficacy data were obtained from the MagnetisMM-3 clinical trial for elranatamab, and from a matching adjusted indirect comparison (MAIC) of elranatamab versus teclistamab and PCT. Utility values were gathered from the MagnetisMM-3 trial for each health state. Only direct costs (2024 €) were considered. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the variables and determine the robustness of the results. Results Treatment with elranatamab is cost-effective compared to PCT, generating 0.92 additional quality-adjusted life years (QALYs) and an additional €17,860 over a lifetime horizon, yielding an incremental cost-effectiveness ratio (ICER) of €24,754/QALY. Elranatamab is dominant (less costly, more effective) versus teclistamab, providing 0.60 additional QALYs and generating cost savings (− €101,026). Sensitivity analyses confirmed the direction of the base case results. Conclusion Elranatamab is a cost-effective treatment versus PCT and dominant over teclistamab for the treatment of adult patients with TCE-RRMM in the Spanish setting.

Trisomy 8 (+ 8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated to clinical heterogeneity and intermediate cytogenetic risk when found isolated. The presence of gene mutations in this group of patients and the prognostic significance has not been extensively analyzed. Targeted-deep sequencing was performed in a cohort of 79 MDS patients showing isolated + 8. The most frequently mutated genes were: TET2 (38%), STAG2 (34.2%), SRSF2 (29.1%) and RUNX1 (26.6%). The mutational profile identified a high risk subgroup with mutations in STAG2, SRSF2 and/or RUNX1, resulting in shorter time to acute myeloid leukemia progression (14 months while not reached in patients without these mutations, p < 0.0001) and shorter overall survival (23.7 vs 46.3 months, p = 0.001). Multivariate analyses revealed the presence of mutations in these genes as an independent prognostic factor in MDS showing + 8isolated (HR: 3.1;p < 0.01). Moreover, 39.5% and 15.4% of patients classified as low/intermediate risk by the IPSS-R and IPSS-M respectively, were re-stratified as high risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort (n = 2 494). In summary, the mutational profile in isolated + 8 MDS patients could offer new insights for the correct management of these patients.