Abstract Topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Background: The wide introduction of different molecular genetic markers has resulted in various scoring models in patients (pts) with multiple myeloma (MM).
Aims: The aim of study was to compare prognostic significance of different scoring systems in newly diagnosed multiple myeloma (NDMM) pts.
Methods: The study included 247 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 myeloma was observed in 16pts (7.5%). According to the Revised-ISS (R-ISS) score, R-ISS1 was found in 61pts (24.7%), R-ISS2 in 160pts (64.8%), while R-ISS3 was present in 26pts (10.5%). According to R2-ISS score, low risk had 61pts (24.7%), intermediate-low 56pts (22.7%), intermediate-high 116pts (47%), and high-risk had 14pts (5.7%). Considering Response-Adjusted ISS (RaISS) score the distribution was: low risk 34 (13.8%), intermediate 108 (43.7%) and high risk 105 (42.7%) pts. Frailty analysis according to IMWG Frailty score (IMWG-FS) was following: frail – 121pts (49%), 76pts (30.8%) of intermediate-fitness, and 50pts (20.2%) were fit. Sarcopenia existed in 142pts (57,5%) according to the SARC-F score.
Treatment with thalidomide (Thal) based triplets was applied in 82pts (33.2%), while 165pts (66.8%) were treated with bortezomib (Bz) based triple combinations. Autologous stem cell transplantation (ASCT) was performed in 79 pts (32%).
Results: Overall response rate (ORR ≥PR, IMWG criteria) was achieved in 215pts (87.04%). There was significant difference between transplant-eligible and non-eligible pts in PFS (Log Rank 10.44, p=0.001) and OS (Log Rank 25.39, p=0.000). Patients with double and triple hit myeloma, had 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 4 score had the worst prognosis regarding PFS (Log Rank 9.60, p=0.002) and OS (Log Rank 13.86, p=0.000). Considering RaISS score, pts with RaISS 0-3 significantly had longer PFS (Log Rank 7.04, p=0.008), as well as OS (Log Rank 18.58, p=0.000). Patients with sarcopenia had significantly shorter PFS (Log Rank 7.68, p=0.006), and OS (Log Rank 27.77, p=0.001). Frail pts with IMWG-FS 2 had significantly OS (Log Rank 19.16, p=0.001). The multivariate analysis pointed out poor prognostic impact to PFS of following variables: R2-ISS 4 score (HR 5.07, 95% CI 1.37-18.8), RaISS 2 (HR 1.67, 95% CI 1.02-2.74), and transplant ineligibility (HR 0.45, 95% CI 0.26-0.79). Similarly, the OS was strongly influenced by R2-ISS 4 (HR 6.53, 95% CI 1.81-23.54), RaISS 2 (HR 1.75, 95% CI 1.06-2.89), and transplant eligibility (HR 0.23, 95% CI 0.11-0.49).
Summary/Conclusion: Biologic characterics as R2-ISS 4 score, have the most significant impact on the course of disease, as well as achievement of CR, represented by Ra-ISS score. The level of transplant-eligibility significance is ameliorated probably due to introduction of new treatment modalities.
Keywords: Molecular markers, Myeloma, Prognosis