PROGNOSTIC IMPACT OF CYTOGENETIC ABNORMALITIES AND R2-ISS IN MULTIPLE MYELOMA

Abstract

Introduction: Cytogenetic abnormalities are crucial for risk stratification and therapeutic decisions in multiple myeloma (MM). The incorporation of 1q+ into the R2-ISS prognostic tool has revealed a new subgroup of very high-risk patients not previously identified by the R-ISS model. Advances in cytogenetic techniques, particularly fluorescence in situ hybridization (FISH), have provided important insights into the clinical and biological behavior of MM. Despite the growing importance of these techniques, cytogenetic analysis is still not widely available in many countries. Our study aims to describe the experience of incorporating cytogenetic analysis and the R2-ISS classification in MM patients at a Brazilian private hospital. Objective: This study aims to describe the experience of incorporating cytogenetic analysis and the R2-ISS classification in MM patients from a Brazilian private hospital. Methods: This is an observational, retrospective, and descriptive study. Data were collected from patients between January 2022 and January 2024. Patients eligible for autologous stem-cell transplantation (autoSCT) were treated with the PERSEUS protocol (Dara-VRd), with 93% achieving responses superior to partial responses. Patients ineligible for autoSCT received the MAIA protocol (Dara-Rd). Complete risk stratification for R-ISS and R2-ISS, including FISH from a bone marrow sample, was required for all patients. Results: A total of 25 patients (16 eligible for autoSCT) were included. The average age was 63 years, with the most common type being IgG Kappa (52%). The median follow-up was 15 months (range: 12-70). Cytogenetic abnormalities were detectable by FISH in 13 out of 25 cases (52%). More than 90% of these findings were classified as high risk by the mSMART 3.0 model. In the transplant-eligible group, 7 out of 16 patients had at least one high-risk cytogenetic mutation, and in the ineligible group, 3 out of 9 patients had such mutations. The most common findings were +1q in 9 cases (36%) and del(13q) in 5 cases. Thirty percent of all cases had a prognostic classification shift when R2-ISS was compared to R-ISS, with most shifts occurring in the R-ISS III group. Of the 10 patients in this classification, 50% were up-staged to R2-ISS IV. The median overall survival (mOS) of all R-ISS III patients was 21 months (range: 2-75). With R2-ISS, the mOS was 36 months (range: 4-75) in R2-ISS III and 9 months (range: 2-19) in R2-ISS IV. The progression-free survival (PFS) for R-ISS III patients was 17 months (range: 1-60). The same population classified with R2-ISS had a PFS of 21 months (range: 8-60) in R2-ISS III and 5 months (range: 1-13) in R2-ISS IV. Conclusions: The incorporation of cytogenetic analysis and the R2-ISS classification in the treatment of MM patients provides a more precise stratification of high-risk patients, particularly revealing a subgroup at very high risk. The R2-ISS seem to be a simple prognostic staging system offering more accurate stratification of MM patients. However, prospective studies with larger cohorts and standardized methodologies for FISH are necessary to further validate these findings and optimize treatment strategies for MM patients.