The independent adverse prognostic significance of 1q21 gain/amplification in newly diagnosed multiple myeloma patients

Abstract

Objective1q21 gain/amplification (1q21+) is a common abnormal karyotype in multiple myeloma, and its proportion in Chinese patients is much higher. If 1q21+ is included as one of the poor prognostic factors, it will greatly increase the proportion of high-risk patients in newly diagnosed multiple myelome (NDMM) patients. Therefore, the poor prognostic significance of 1q21+ is still controversial. This study mainly analyzed the clinical characteristics, treatment response and prognostic significance of 1q21+ in NDMM patients.Methods248 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2021 of a VRD registration study, were retrospectively analyzed. 135 cases (54.4%) had 1q21+ by CD38-sorted fluorescence in situ hybridization (FISH). The clinical characteristics, treatment response and prognosis of the general population and subgroups were analyzed, among which 153 patients were compared for the involved genes by CytoScan.ResultsCompared with negative patients, 1q21+ patients were more likely to have anemia, hypoalbuminemia, renal insufficiency, high lactate dehydrogenase and high proportion of R-ISS-III stage. The patients with 1q21+ involving CKS1B detected by Cytoscan had a higher proportion of complex karyotypes and abnormal CNVs, and all at middle-risk or high-risk groups defined by Prognostic Index. Multivariate analysis showed that 1q21+ was an independent adverse prognostic factor (PFS HR=2.358, 95%CI 1.286-4.324, P=0.006; OS HR=2.598, 95%CI 1.050-6.425, P=0.039). 1q21+ subgroup had an inferior outcome (PFS P=0.0133, OS P=0.0293). Furthermore 1q21 amplification had a shorter PFS than 1q21 gain (24 months vs not reached, P=0.0403), but the OS difference was not clinically significant. The proportion of 1q had no effects on prognosis. In addition, 1q21+ in main clone rather than subclone was an adverse factor affecting the prognosis (PFS P=0.0172, OS P=0.1260). Autologous stem cell transplantation can effectively improve the survival of 1q21+ patients (P<0.05).ConclusionPatients with 1q21+ have clinically significant end-stage organ damage and higher tumor burden, more likely to combine 13q14-, t(4;14), 1p32- and other cytogenetic abnormalities. 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in NDMM patients, of which 4 or more copy numbers and main clone position significantly associated with prognosis results.

The prognostic significance of 1q21 gain/amplification in newly diagnosed multiple myeloma： a single‑center real world retrospective study of China

“…In recent years, 1q21+ has been identi ed as a potential poor prognostic factor [22,26], but the importance of 1q21 copy number in MM patient prognosis remains contradictory. You H et al [10] reported that the 1q21 amp had a shorter PFS than the 1q21 gain, but not the OS. Wang YT et al [6] considered that amp 1q21 alone correlated with shorter PFS and OS compared with gain 1q21 alone and no FISH abnormalities.…”

“…The main types of 1q21+ are isochromosomes, duplications, or jumping translocations, leading to the chromosomal instability of MM cells, which may be due to the genetic complexity and heterogeneity of patients carrying multiple copies of 1q21 and multiple genes. Several studies have identi ed the poor prognostic impact of 1q21 accompany [10][11][12], but the signi cance of copy number and clone size remains con icting [13,14]. The presence of 1q21+ may also be associated with other HRCAs, such as t(4;14) and t(14;16), or with 13q deletion[6, [13][14][15][16].…”

The numerous facets of 1q21+ in multiple myeloma: Pathogenesis, clinicopathological features, prognosis and clinical progress (Review)

“…There are also differences with the aforementioned views. Several studies have revealed that the prognosis of patients with MM is worse when 1q21 copy number ≥4; for instance, You et al (28) revealed that 1q21 amplification had worse PFS than 1q21 gain (24 months vs. not reached, P=0.0403). Neben et al (77) discovered that a 1q21 copy number of three has a marginal negative effect, and having more than three copies significantly reduces PFS and OS.…”

“…In recent years, the introduction of autologous hematopoietic stem cell transplantation (ASCT), immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and an anti-CD38 monoclonal antibody have greatly improved the outcomes of patients with MM (23)(24)(25)(26). However, the overall survival (OS) of patients with MM and 1q21 + remains to be improved (27,28). In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21 + were reviewed, the key data of 1q21 + on the prognosis of patients with MM were summarized and the clinical treatment significance of MM patients with 1q21 + were clarified, for the purpose of providing reference for clinicians to develop treatment strategies targeting 1q21 + .…”

Current Main Topics in Multiple Myeloma

“…Differently from previous scores, abnormalities of 1q were included in the R2-ISS, as also recommended by NCCN MM Panel [ 21 ], without a distinction between gain (3 copies) and amplification (>3 copies), although this would further improve the risk stratification. It was recently described that amp1q and its main clone position could be significantly associated with prognosis results, in comparison with gain1q [ 22 , 23 , 24 , 25 ], even if the biological meaning of amp1q remains difficult to determine. A recent retrospective experience confirmed the greater role of the association of high risk feature rather than a single one, but also the size of high risk clone influenced prognosis [ 26 ].…”