P-107: The second revision of international staging system (R2-ISS) in newly diagnosed multiple myeloma patients: RWE settings

Introduction: The recent introduction of R2-ISS scoring system brought better risk stratification of patients (pts) with newly diagnosed multiple myeloma (NDMM). The aim of study was to analyze prognostic significance of R2-ISS score in NDMM pts within RWE settings.

Methods: Analyzed group included 247 transplant ineligible NDMM pts, diagnosed during period 2017-2021 (128 male; 119 female, mean age 63 yrs, range 37-82). The IgG myeloma was diagnosed in 149pts (60.3%), IgA in 50 (20.2%), BJ in 48 (19.4%), non-secretory MM in 3pts (1.2%). Renal impairment was present in 73pts (29.6%). Double and triple hit MM was observed in 16pts (7.5%). Stratification according to Revised-ISS (R-ISS) score was as follows: R-ISS1 in 61pts (24.7%), R-ISS2 in 160pts (64.8%), while R-ISS3 was present in 26pts (10.5%). Treatment with Thalidomide (Thal) based triplets was applied in 82pts (33.2%), while 165pts (66.8%) were treated with Bortezomib (Bz) based triplet combinations.

Results: According to newly presented R2-ISS score, low risk MM had 61pts (R2-ISS 1 24.7%), intermediate-low 56pts (R2-ISS 2 22.7%), intermediate-high 116pts (R2-ISS 3 47%), and high-risk had 14pts (R2-ISS 4 5.7%). Overall response rate (ORR ≥PR) was achieved in 215pts (87.04%). Finding of double and triple hit MM was characterized with significantly shorter PFS (Log Rank 6.37, p=0.012) and OS (Log Rank 6.57, p=0.010), compared to standard risk pts. Patients with R2-ISS 1 score had median PFS 46 months (range: 41.2-51.8m), R2-ISS 2 group had 38.5m (range: 33.6-43.4m), R2-ISS 3 36.9m (range: 29.7-44.2m) and R2-ISS 4 group had the shortest PFS, 28.8m (range: 12.9-44.7m). Median OS was as follows: R2-ISS 1 55.4m (range: 51.6-59.3m), R2-ISS 2 44.2m (range: 39.9-48.5m), R2-ISS 3 41.5m (range: 35.3-47.7m), R2-ISS 4 29.2m (range: 16.2-42.2m). There was a significant difference in OS according to R2-ISS score (log rank=19.52, p˂0.001). Although a higher R2-ISS score was associated with shorter PFS, statistical significance was not proved among different R2-ISS groups (log rank=7.41, p=0.060). Still, R2-ISS 4 score had the worst prognosis regarding PFS (Log Rank 9.60, p=0.002) and OS (Log Rank 13.86, p=0.000) in comparison to pts with lower risk scores. The multivariate analysis of following variables: age, elevated LDH, double and triple hit MM, R-ISS and R2-ISS score, pointed out the most pronounced poor prognostic impact to PFS of R2-ISS 4 score (HR 5.07, 95% CI 1.37-18.8). Similarly, OS was also influenced by the presence of high-risk R2-ISS score 4 (HR 6.53, 95% CI 1.81-23.54).

Conclusions: Newly presented R2-ISS score is applicable and powerful prognostic tool, more sensitive in comparison to classic R-ISS score, thus better identifying MM pts with high risk features.