P-238: Prognostic impact of cytogenetic abnormalities and R2-ISS in multiple myeloma: experience in a Brazilian private hospital

Introduction: Advances in cytogenetic techniques, notably the Fluorescence In Situ Hybridization (FISH), has brought important data about the clinical and biological behavior of multiple myeloma (MM). Cytogenetic abnormalities are useful for risk stratification and therapeutic decisions. The incorporation of 1q+ into the R2-ISS prognostic tool revealed a new subgroup of very high-risk patients, not previously found in the R-ISS model. Cytogenetic analysis is still not widely available in many countries. This work objective was describe the experience of incorporating cytogenetic analysis and the R2-ISS classification MM patients from a Brazilian private hospital.

Methods: This is an observational, retrospective and descriptive study. Patient’s data collected from January 2022 to January 2024. Patients eligible for autologous stem-cell transplantation (autoSCT) were treated with the PERSEUS protocol (Dara-VRd), with 93% of patients achieving responses superior than partial responses. Patients ineligible for autoSCT receveid the MAIA protocol (Dara-Rd). Patients were required to have a complete risk stratification for R-ISS and R2-ISS, including FISH from a bone marrow sample.

Results: 25 patients (of which 16 eligible for autoSCT) were included. Average age was 63 years. The most common type was IgG Kappa (52%). Median follow-up of 15 months (12-70). 13/25 (52%) cases had detectable cytogenetic abnormality on FISH. More than 90% of all findings were classified as high risk by the mSMART 3.0 model. 7/16 and 3/9 patients had at least one high-risk cytogenetic mutation in the transplant eligible and ineligible groups, respectively. The most common findings were +1q in 9 cases (36%) and del(13q) in 5 cases. 30% of all cases had a prognostic classification shift when R2-ISS was compared to R-ISS. Most shifts occurred in the R-ISS III group. Of the 10 patients in this classification, 50% received up-staging to R2-ISS IV. The median overall survival (mOS) of all R-ISS III patients was 21.3 months (2-75). With R2-ISS, the mOS of the III group was 36 mo (4-75) and 8.8 mo (2-19) in the IV subset. The progression-free survival (PFS) for the R-ISS III patients was 17.12 mo (1-60). The same population classified with R2-IPSS had a PFS of 21.3 mo (8-60) in group III and 5 mo (1-13) in group IV.

Conclusions: Real-life data suggests that applying R2-ISS reveals a subgroup of patients at higher risk (IV), not previously found in the R-ISS III stage. The group IV seems to have a lower mOS and mPFS when compared to the other stages. There is a need of prospective studies with large cohorts and standardization of FISH reports and methodologies for the better understanding of prognosis and clinical outcome of multiple myeloma.