The paradoxical prognostic role of 1q21 Gain/Amplification in multiple myeloma: every coin has two sides

Xu, Jiadai; Xu, Tianhong; Yang, Yang; Wang, Wenjing; Li, Jing; Ren, Yuhong; Gu, Shengqing; Chen, Chen; Wei, Zheng; Jing, Zhuang; Wang, Zhimei; Ji, Lili; Cheng, Luya; Wang, Weiguang; Cheng, Zhigang; Ke, Yang; Yuan, Ling; Liu, Peng

doi:10.1080/10428194.2020.1772473

Cited by 11 publications

(12 citation statements)

References 28 publications

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“…The survival outcomes exhibited consistent similarity between the patients with 1q gain (n = 208, 61.7%) and those with 1q amp (n = 129, 38.3%) are displayed in Figures 1B,E, which agreed with our previous findings. 24 The clone size of this 1q gain/amp ranged from 4% to 95%. According to the results of maximal χ 2 analysis, the clone size of 29% was the optimal cutoff point of 1q gain/amp that distinguished two prognostic groups most effectively.…”

Section: Impact Of 1q Copy Number and Clone Size On Survivalmentioning

confidence: 97%

The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse

et al. 2023

Cancer

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Background:The prognostic value of additional copies of chromosome 1q (1q gain/ amplification [amp]) in multiple myeloma (MM) remains controversial. In the meantime, the kinetics of the response to MM therapy has long been an area of debate. Few studies have pointed out the relationship of response kinetics with cytogenetic abnormalities (CAs) in MM. Methods:The authors retrospectively analyzed the data of 1068 real-world newly diagnosed MM patients from a Chinese national medical center. Results: Overall, 405 (51.9%) patients had 1q gain/amp, with aggressive clinical characteristics and significant inferior survival. The variation in copy number (CN) of 1q (CN = 3 or CN >3) had no significant impact on the survival of MM patients with 1q abnormalities. No difference was found in the outcome of 1q gain/amp patients treated with doublet or triplet regimens. Upfront autologous stem cell transplantation could eliminate the adverse prognostic effect of 1q gain but not 1q amp. The duration from diagnosis to the first time achieving very good partial response (VGPR) or better was significantly shorter in patients with 1q gain/amp (77 days vs. 100 days, p = .001). Finally, multifactor regression analysis was performed to construct a new risk stratification model in MM patients with 1q gain/amp, which was validated in the Multiple Myeloma Research Foundation CoMMpass study cohort and worked better than the Revised International Staging System and Second Revision of the International Staging System (Harrell's concordance index: 0.631 vs. 0.598 and 0.537). Conclusions:In the setting of novel therapy, 1q gain/amp still acts as an independent adverse prognostic factor. Patients with 1q gain/amp achieved VGPR rapidly but had inferior survival.

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Section: Impact Of 1q Copy Number and Clone Size On Survivalmentioning

confidence: 97%

The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse

et al. 2023

Cancer

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“…The amp 1q21 had profound adverse effect compared with gain 1q21, 7 while other researches have shown the similar characteristic and survival of patients with gain 1q21 and amp 1q21. 11 According to the clone heterogeneity of MM, 1q21+ were more likely accompanied with other HRCAs, including t(4;14), t(14;16), t (14;20), del(1p), and del(13q). 11,12 Previous studies have demonstrated that only amp 1q21 with additional HRCAs was negative predictor for newly diagnosed MM (NDMM) treated with thalidomide.…”

Section: Patient Characteristics (Age Eastern Cooperativementioning

confidence: 99%

“…11 According to the clone heterogeneity of MM, 1q21+ were more likely accompanied with other HRCAs, including t(4;14), t(14;16), t (14;20), del(1p), and del(13q). 11,12 Previous studies have demonstrated that only amp 1q21 with additional HRCAs was negative predictor for newly diagnosed MM (NDMM) treated with thalidomide. 13,14 Recent research also defined amp 1q21 as a parameter of double hit in era of new drugs.…”

Section: Patient Characteristics (Age Eastern Cooperativementioning

confidence: 99%

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Amp 1q21 is more predictable with dismal survival than gain 1q21 of newly diagnosed multiple myeloma in real‐world analysis

Wang

Cui

et al. 2022

Clinical Laboratory Analysis

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Introduction:The gain/amplification (amp) of 1q21 is one of the most common highrisk chromosome abnormality (HRCA) in multiple myeloma (MM). The prognostic value of 1q21+ remains to be controversial on the status of gain or amp and the combination of other HRCAs. Methods:In this retrospective study, we included 318 newly diagnosed MM (NDMM) patients who had fluorescence in situ hybridization (FISH) data and treated with novel agents in our department.Results: Our study noted MM patients with amp 1q21 were more likely accompanied with t(4;14), t(14;16), and t(14;20). Patients with amp 1q21 presented with elder age, advanced Revised International Staging System (R-ISS) stages, anemia, and more plasma cells in bone marrow compared to patients with gain 1q21 alone and no 1q21+. Moreover, amp 1q21 alone correlated with shorter progression-free survival (PFS) (22.8m vs. 40.5m vs. 39.6m) and overall survival (OS) (45.2m vs. NA vs. 83.5m) compared with gain 1q21 alone and no FISH abnormalities. Although the high ratio of proteasome inhibitor and immunomodulatory drugs used in patients with amp 1q21, the overall response (ORR) was the lowest compared with no 1q21+ and gain 1q21. Multivariate analysis defined amp 1q21 as an independent prognostic marker for NDMM patients, rather than gain 1q21. Conclusion:The amp 1q21 predict inferior treatment response and survival, especially coexisted with high-risk IgH translocation.

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“…1,2 Gain of 1q22 at diagnosis has also emerged as an HR cytogenetic feature; patients with this abnormality often present with more aggressive clinical features and disease, with significant reduction in overall survival (OS) and progression-free survival (PFS) even upon controlling for concomitant HR cytogenetic abnormalities. [3][4][5][6][7][8][9][10]…”

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confidence: 99%

Prognostic significance of acquired 1q22 gain in multiple myeloma

et al. 2021

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Gain of 1q22 at diagnosis portends poorer outcomes in multiple myeloma (MM), but the prognostic significance of acquired 1q22 gain is unknown. We identified 63 MM patients seen at Mayo Clinic from 1/2004 to 12/2019 without 1q22 gain at diagnosis who acquired it during follow up and compared them to 63 control patients who did not acquire 1q22 gain with similar follow up. We also compared outcomes in the acquired 1q22 gain group with outcomes in 126 patients with 1q22 gain present at diagnosis. The incidence of acquired 1q22 gain was 6.1% (median follow-up 6.8 years); median time to acquisition was 5.0 years (range: 0.7-11.5 years). Abnormalities on baseline fluorescence in situ hybridization (FISH) included trisomies (54%) and monosomy 13 (39%); 16 (25%) had high-risk (HR) translocations or del(17p).Median progression-free survival with front line therapy was 29.5 months in patients with acquired 1q22 gain, versus 31.4 months in control patients (p = .34) and 31.2 months in patients with de novo 1q22 gain (p = .04). Median overall survival (OS) from diagnosis was 10.9 years in patients with acquired 1q22 gain, versus 13.0 years in control patients (p = .03) and 6.3 years in patients with de novo 1q22 gain (p = .01). Presence of HR FISH at baseline increased risk of 1q22 gain acquisition. We demonstrate that acquisition of 1q22 gain is a significant molecular event in MM, associated with reduced OS. Among HR patients for whom this clonal evolution is determined, a risk-adapted approach and/or clinical trial should be considered. | INTRODUCTIONMultiple myeloma (MM) has a heterogeneous genomic landscape, with several karyotypic abnormalities having been shown to significantly and differentially affect clinical outcomes. Translocations (4;14, 14;16) and deletion of 17p [del(17p)] have long been defined as high-risk (HR) aberrations. 1,2 Gain of 1q22 at diagnosis has also emerged as an HR cytogenetic feature; patients with this abnormality often present with more aggressive clinical features and disease, with significant reduction in overall survival (OS) and progression-free survival (PFS) even upon controlling for concomitant HR cytogenetic abnormalities. [3][4][5][6][7][8][9][10]

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The paradoxical prognostic role of 1q21 Gain/Amplification in multiple myeloma: every coin has two sides

Cited by 11 publications

References 28 publications

The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse

The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse

Amp 1q21 is more predictable with dismal survival than gain 1q21 of newly diagnosed multiple myeloma in real‐world analysis

Prognostic significance of acquired 1q22 gain in multiple myeloma

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