P-211: Clinical characteristics and prognostic values of 1p32.3 deletion in newly diagnosed multiple myeloma patients

Introduction:
1p32.3 deletion is a common cytogenetic abnormality in multiple myeloma, but its clinical significance has not been clearly demonstrated and its detection by FISH has not been widely carried out. This study mainly analyzed the clinical characteristics, treatment response, and prognostic significance of 1p32.3 deletion detected by Cytoscan in newly diagnosed multiple myeloma patients.

Methods: 345 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2022 of a VRD registration study, were retrospectively analyzed. Cytogenetic testing was performed by CD138 sorted fluorescence in situ hybridization (FISH) and Cytoscan.

Results:
The proportion of chromosomal 1 abnormalities was 64.1%, including 189 cases (54.8%) of 1q21 gain/amplification and 88 cases (25.5%) of 1p deletion. Among them, 40 patients had 1p32.3 locus and involved CDKN2C deletion. Del1p32.3 patients had higher urinary protein levels, higher LDH levels and were more likely accompanied with extramedullary disease, strongly correlated with 1q21 gain/amplification and 17p deletion. Cytoscan showed the higher proportion of complex chromosomal abnormalities, different subclonal groups, complex karyotypes and CNV abnormalities. 1p32.3 showed the increased proportion of disease progression and lower achievement of deeper remission after induction therapy. Patients with single monoallelic deletion have significantly poorer survival outcomes compared to those with partial chimeric monoallelic deletion both in 1p12, 1p22 and 1p32.3 locus, with the shortest median PFS of only 15 months, P=0.0110, and the shortest median OS of only 18 months, P=0.0015. The main clone is a clear adverse factor affecting patient prognosis (median PFS 15 months, P=0.0103, median OS not reached, P=0.0167).The accumulation of HRCAs could further deepen the adverse prognosis of high-risk patients in PFS (median PFS 20 months, PFS P=0.0480, OS P=0.1074). Autologous stem cell transplantation can improve the prognosis in Del1p32.3 population in both PFS and OS to some extent (36 months PFS 50.6% vs 37.5%, 36 months OS 82.5% vs 70%). In multivariate analysis, only 1p32.3 was an independent adverse factor affecting the prognosis of PFS in patients with 1p deletion (PFS: HR=1.755, 95% CI 1.060-2.907, P=0.019; OS: HR=1.291, 95% CI 0.608-2.743, P=0.506).

Conclusions: Patients with 1p32.3 deletion are prone to high-risk cytogenetic abnormalities, and 1p32.3 deletion is an independent high-risk cytogenetic factor for poor prognosis of MM, associated with unstable disease cloning and invasive phenotype of plasma cell diseases, indicating it should be routinely tested in the clinic for newly diagnosed MM patients.