Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens

Liu, Xiao; Jia, Shuangshuang; Chu, Yuping; Tian, Biao; Gao, Yaya; Zheng, Yanhua; Jia, Weijing; Liu, Xiangxiang; Yuan, Ruifeng; Zhang, Na; Feng, Juan; Dong, Hongjuan; Xin, Xiaoli; Chang, Ziwei; Cao, Zhengcong; Tang, Hongwei; Gao, Guangxun

doi:10.3389/fonc.2022.938550

Cited by 5 publications

(6 citation statements)

References 25 publications

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“… 4 , 10 , 11 Although there are controversies, most researchers considered that patients with 1q21 gain/Amp had shorter durations of PFS and OS than patients without this cytogenic abnormality. 12 – 14 This means that a deeper response may not indicate a survival benefit. Some studies have discussed the relationship between response dynamics and survival.…”

Section: Discussionmentioning

confidence: 99%

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

Zhou,

Wen,

et al. 2024

Technol Cancer Res Treat

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Objective 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. Methods Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. Results Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy ( P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III ( P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 ( P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. Conclusions When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.

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Section: Discussionmentioning

confidence: 99%

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

Zhou,

Wen,

et al. 2024

Technol Cancer Res Treat

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“…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. Liu X et al [27] showed that after excluding the effects of other coinciding genetic anomalies, patients with 1q21amp had worse survival outcomes. Some studies had shown that the copy number of 1q21 had no additional prognostic impact [7,13,16].…”

Section: Discussionmentioning

confidence: 99%

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

Deng

Chen

2023

Preprint

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The gain or amplification 1q21(1q21+) is the most common abnormality in multiple myeloma, but their prognostic impact remains under debate in the era of novel agents. In addition, the prognosis of the 1q21 copy number is controversial. In this retrospective study, cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) and clinical outcomes of 375 newly diagnosed MM patients were analyzed. 1q21 + was detected in 164 (43.7%) patients, including 103 (27.5%) with 3 copies and 61(16.3%) with ≥4 copies. Patients with 1q21 were more likely to be accompanied by anemia and hypercalcemia and were also associated with the accompaniment of other high-risk cytogenetics abnormalities (HRCAs) such as t (4;14), t(14;16) (p༜0.001; p = 0.002 ). The median progression-free survival (PFS) of 1q21-, 1q21 gain, and 1q21 amp was not reached (NR), 35 months and 21 months, respectively (p < 0.001), and the median overall survival (OS) was NR, 56 months and NR, respectively (p = 0.049). And compared with 1q21gain, 1q21 amp has shorter PFS (p = 0.007), but not the OS (p = 0.258). Meanwhile, there was no difference outcome of survival between patients with 1q21gain alone,1q21amp alone, and FISH-. When accompanied by different HRCAs, 1q21 showed earlier disease progression than 1q21 + alone and FISH-. Combined application of proteasome inhibitors (PIs) and immunomodulators (IMiDs) could improve the poor prognosis of 1q21 partly, and autologous stem cell transplantation (ASCT) could prolong the survival of 1q21 + patients (p༜0.001). Hence, when coexisted with other cytogenetics abnormalities (CAs), 1q21 showed a relatively poor prognosis, especially 1q21amp.

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“…Similarly, Schmidt et al (82) and Gao et al (89) both revealed that copy number of 1q21 ≥4 led to a poor prognosis. In a recent retrospective study of 794 patients with MM, the median PFS times of normal copy number of 1q, 1q gain and 1q amplification were 49, 50 and 26 months, respectively (P=0.268), and the median OS times were NR, NR and 41 months, respectively (P= 0.001), suggesting that 1q21 amplification had a greater negative impact on prognosis than 1q21 gain (90). This might be related to the dose response of genes in the chromosome 1q region.…”

Section: Impact Of 1q21 + On Prognosismentioning

confidence: 99%

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

Liu,

Xie,

et al. 2024

Oncol Lett

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Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells (PCs) in the bone marrow and recurrent cytogenetic abnormalities. The incidence of MM worldwide is on the rise. 1q21 + has been found in ~30-40% of newly diagnosed MM (NDMM) patients.1q21 + is associated with the pathophysiological mechanisms of disease progression and drug resistance in MM. In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21 + were studied, the key data of 1q21 + on the prognosis of MM patients were summarized, and the clinical treatment significance of MM patients with 1q21 + was clarified, in order to provide reference for clinicians to develop treatment strategies targeting 1q21 + . Contents 1. Introduction 2. Pathogenesis and clinicopathological features of 1q21 + in patients with MM 3. Impact of 1q21 + on prognosis 4. Treatment of MM patients with 1q21 + 5. Conclusions

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Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens

Cited by 5 publications

References 25 publications

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

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

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

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Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens

Cited by 5 publications

References 25 publications

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp

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

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

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