Proposed risk‐scoring model for estimating the prognostic impact of 1q gain in patients with newly diagnosed multiple myeloma

Abstract

1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007).Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort.While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their Peiyu Yang and Haimin Chen contributed equally to this study.

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

“…In this study, we report a real-world retrospective study of the prognosis of 1q21+ in newly diagnosed multiple myeloma patients in the new novel agent. We found that 1q21+ was a common event with an incidence rate of 43.7% in NDMM, by previous studies[8, [19][20][21], but slightly lower than some other studies [10,13,22]. From the perspective of clinical characteristics, the presence of 1q21+ is associated with other adverse prognostic factors such as anemia and hypercalcemia[6, 10,14].…”

“…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.…”

The R2-ISS in a Multicenter Cohort of Chinese Patients With Newly Diagnosed Multiple Myeloma

“… 13 Considering the significance of 1q+ in the R2-ISS, the Chinese population of NDMM patients may be particularly susceptible to this scoring system due to their high frequency (~50% of NDMM patients) of 1q+ and its prognostic value as reported earlier by our group. 14 …”

“…All patients had given written informed consent to the use of clinical data according to the Declaration of Helsinki. The inclusion criteria of this study were patients who had complete baseline information for R2-ISS scoring, particularly involving cytogenetics in CD138 + cells by fluorescence in-situ hybridization (FISH) that must include the probes for del(17p) (cutoff, 20%), t(4;14) (cutoff, 7.3%), and 1q+ (cutoff, 5.5%) including gain (3 copies) and amplification (≥4 copies) as described previously, 14 and who must receive novel agents (PIs, IMiDs, or both) for upfront treatment. It is noteworthy that the cutoffs for some HRCAs such as t(4;14) and 1q+ was lower than those usually recommended, which might, at least in part, contribute to a relatively higher percentage of high-risk patients (eg, 1q+) in this cohort, thus representing one limitation of this study.…”

“…13 Considering the significance of 1q+ in the R2-ISS, the Chinese population of NDMM patients may be particularly susceptible to this scoring system due to their high frequency (~50% of NDMM patients) of 1q+ and its prognostic value as reported earlier by our group. 14 To this end, we carried out a retrospective analysis of the real-world data collected from daily practice to further validate the R2-ISS in a cohort of 1005 MM patients newly diagnosed between November 27, 2009 and November 20, 2019, at 6 centers nationwide in China (Table 1). This study was approved by the Institutional Review Boards of the First Hospital of Jilin University (Approval No.…”