Poor prognosis of newly diagnosed multiple myeloma patients with 1p32.3 deletion in single monoallelic deletion and/or in main clone

Abstract

Del(1p32.3) by FISH detection in multiple myeloma (MM) has not been routinely carried out in China. Its clinical significance was not clearly demonstrated. This study analysed clinical characteristics, treatment response and prognostic significance of del(1p32.3). We analysed 345 newly diagnosed multiple myeloma (NDMM) samples, and cytogenetic analysis was performed using Cytoscan and FISH results, enabling comprehensive disease-specific cohort analysis and prognostic model development. The total proportion of chromosomal 1 abnormality was 64.1%, including 189 cases of 1q21 gain/amplification and 88 cases of 1p deletion, 40 patients had 1p32.3/CDKN2Cdeletion. Del(1p32.3) patients were strongly correlated with 1q21 gain/amplification and 17p deletion. Del(1p32.3) patients were more likely accompanied with extra-medullary multiple myeloma (EMM) and complex karyotype. Del(1p32.3) had a worse effect on progression-free survival (PFS) and overall survival (OS), alongside other high-risk cytogenetic abnormalities that further worsened prognosis, especially 1q gain/amplification. Patients with 1p32.3 in the main clone or with a single monoallelic deletion had significantly poorer survival outcomes. Autologous stem cell transplantation (ASCT) cannot completely overcome its adverse effects on prognosis. In multivariate analysis, 1p32.3 was an important independent adverse PFS factor. Patients harbouring single monoallelic del(1p32.3) and/or main clone deletions demonstrated inferior outcomes despite lenalidomide, bortezomib and dexamethasone (VRD) induction and transplantation. Del(1p32.3) had synergistic effects frequently co-occurring with 1q21 gain/amplification, thus, we strongly advocate for routine del(1p32.3) testing in clinical practice.