A predictive risk-scoring model for survival prognosis of multiple myeloma based on gain/amplification of 1q21: Experience in a tertiary hospital in South-Western China.

BACKGROUND: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. METHODS: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the ß-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models. RESULTS: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4. CONCLUSION: The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.

Case of B-acute lymphoblastic leukaemia with t(1;19)(q23;p13.3) TCF3::PBX1 and co-occurring CBL mutation in an elderly patient.

The t(1;19) (q23;p13) TCF3::PBX1 is a well-described, recurring chromosomal abnormality in B-acute lymphoblastic leukaemia (B-ALL) that has historically been associated with a worse prognosis in paediatric patients. Gene expression profiling has demonstrated that TCF3::PBX1 results in a distinct subtype of B-ALL, leading to its recognition in the most recent WHO and ICC classifications. Though initially believed to be a poor prognostic sign in the adult population, emerging evidence suggests its presence may instead be intermediate or even favourable in B-ALL. However, adults with TCF3::PBX1 are typically younger and often qualify for treatment with paediatric-inspired regimens. Thus, the prognostic significance in this population remains unclear. This translocation appears to be very rare in older adults with B-ALL and its predictive and prognostic nature in this population is unknown. Herein, we explore a case of this translocation occurring in a patient in her 70s. She initially presented to the emergency department with abdominal pain and thrombocytopenia and was subsequently diagnosed with B-ALL. In addition to t(1;19) (q23;p13), a pathologic mutation in the CBL gene was identified. CBL mutations have been implicated in cancer progression and are mostly described in paediatric B-ALL. She was treated with modified Ph-negative EWALL induction (Vincristine, Idarubicin, dexamethasone) and achieved a complete remission. However, she subsequently experienced an early relapse and was refractory to targeted therapy with blinatumomab. After treatment with inotuzumab ozogamicin, she achieved a second complete remission. Unfortunately, she then suffered a central nervous system (CNS) relapse and passed away from complications of her disease. This case serves as an example of the heterogeneous nature of B-ALL. It demonstrates that patients with ostensibly favourable prognostic factors may experience poor response rates to traditional chemotherapy as well as targeted salvage agents. It also illustrates the challenges of treating B-ALL in the elderly population.

Glass syndrome derived from chromosomal breakage downstream region of SATB2.

BACKGROUND: Glass syndrome, derived from chromosomal 2q33.1 microdeletions, manifests with intellectual disability, microcephaly, epilepsy, and distinctive features, including micrognathia, down-slanting palpebral fissures, cleft palate, and crowded teeth. Recently, SATB2 located within the deletion region, was identified as the causative gene responsible for Glass syndrome. Numerous disease-causing variants within the SATB2 coding region have been reported. OBJECTIVE: Given the presentation of intellectual disability and multiple congenital anomalies in a patient with a de novo reciprocal translocation between chromosomes 1 and 2, disruption of the causative gene(s) was suspected. This study sought to identify the causative gene in the patient. METHODS: Long-read whole-genome sequencing was performed, and the expression level of the candidate gene was analyzed. RESULTS: The detection of breakpoints was successful. While the breakpoint on chromosome 1 disrupted RNF220, it was not deemed to be a genetic cause. Conversely, SATB2 is located in the approximately 100-kb telomeric region of the breakpoint on chromosome 2. The patient's clinical features resembled those of previously reported cases of Glass syndrome, despite the lack of confirmed reduced SATB2 expression. CONCLUSION: The patient was diagnosed with Glass syndrome due to the similarity in clinical features. This led us to hypothesize that disruption in the downstream region of SATB2 could result in Glass syndrome. The microhomologies identified in the breakpoint junctions indicate a potential molecular mechanism involving microhomology-mediated break-induced repair mechanism or template switching.

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.

A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis.

Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.

Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells.

Additional copies of chromosome 1 long arm (1q) are frequently found in multiple myeloma (MM) and predict high-risk disease. Available data suggest a different outcome and biology of patients with amplification (Amp1q, ≥4 copies of 1q) vs. gain (Gain1q, 3 copies of 1q) of 1q. We evaluated the impact of Amp1q/Gain1q on the outcome of newly diagnosed MM patients enrolled in the FORTE trial (NCT02203643). Among 400 patients with available 1q data, 52 (13%) had Amp1q and 129 (32%) Gain1q. After a median follow-up of 62 months, median progression-free survival (PFS) was 21.2 months in the Amp1q group, 54.9 months in Gain1q, and not reached (NR) in Normal 1q. PFS was significantly hampered by the presence of Amp1q (HR 3.34 vs. Normal 1q, P < 0.0001; HR 1.99 vs. Gain1q, P = 0.0008). Patients with Gain1q had also a significantly shorter PFS compared with Normal 1q (HR 1.68, P = 0.0031). Concomitant poor prognostic factors or the failure to achieve MRD negativity predicted a median PFS < 12 months in Amp1q patients. Carfilzomib-lenalidomide-dexamethasone plus autologous stem cell transplantation treatment improved the adverse effect of Gain1q but not Amp1q. Transcriptomic data showed that additional 1q copies were associated with deregulation in apoptosis signaling, p38 MAPK signaling, and Myc-related genes.

[The Prognostic Value of Del(1p32) in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To analyze the prognostic value of del(1p32) in patients with newly diagnosed multiple myeloma (MM). METHODS: The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed. Clinical characteristic combined with genetic features, especially del(1p32), were analyzed for survival and prognostic of patients. RESULTS: Among the 341 patients with newly diagnosed MM, 24(7.0%) patients were del(1p32) positive. The progression-free survival (PFS) and overall survival (OS) were significantly shorter in MM patients with del(1p32) than those without del(1p32) (PFS: P < 0.001;OS: P < 0.001). The COX proportional-hazards model showed that del (1p32) was an independent risk factor for PFS and OS of patients with MM. The patients with both 1q21 gain/amplification and del(1p32), as "double-hit chromosome 1", have worse prognosis than those with only 1q21 gain/amplification or only del(1p32) (PFS: P < 0.001; OS: P < 0.001). CONCLUSION: Del(1p32) is an independent risk factor for PFS and OS of patients with MM. Del(1p32) detection should be widely used in the prognostic analysis for newly diagnosed MM patients.

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

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.

1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma.

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells.

MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Chromosome-specific induction of micronuclei and chromosomal aberrations by mitomycin C: Involvement of human chromosomes 9, 1 and 16.

Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6-8-fold but the frequency of chromosome 9 -positive (9+) MN by 29-30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12-16-fold and 10-17-fold, respectively. After treatment with MMC, 34-47 % of all MN were 9+, 17-20 % 1+, and 3-4 % 16+. The majority (94-96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12.

Anti-CD38 monoclonal antibodies in multiple myeloma with gain/amplification of chromosome arm 1q: a review of the literature.

INTRODUCTION: Gain/amplification of 1q (+1q) represents one of the most prevalent cytogenetic abnormalities (CAs) observed in multiple myeloma (MM). Historical studies predating the advent of anti-CD38 monoclonal antibodies (moAbs) implicated + 1q in poor prognoses, prompting its integration into novel staging systems. However, with the emergence of daratumumab and isatuximab, two pivotal anti-CD38 moAbs, the landscape of MM therapy has undergone a profound transformation. AREAS COVERED: This review encompasses a comprehensive analysis of diverse study methodologies, including observational investigations, clinical trials, meta-analyses, and real-world database analyses. By synthesizing these data sources, we aim to provide an overview of the current understanding of + 1q in the context of anti-CD38 moAbs therapies. EXPERT OPINION: Despite the paucity of available data, evidence suggests a potential mitigating effect of daratumumab on the adverse prognostic implications of + 1q. However, this benefit seems to diminish in patients harboring ≥ 4 copies or with concurrent high-risk CAs. On the other hand, isatuximab demonstrated promising outcomes in the relapsed-refractory setting for + 1q MM patients. Nevertheless, direct comparison between the two compounds is currently challenging. The current evidence firmly supports the integration of anti-CD38 moAb-based therapies as the standard of care for + 1q patients, pending further elucidation.

Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma.

Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a "two-step" process in the clonal size changes of gain/amp(1q) in MM.

Different Nuclear Architecture in Human Sperm According to Their Morphology.

Human sperm parameters serve as a first step in diagnosing male infertility, but not in determining the potential for successful pregnancy during assisted reproductive technologies (ARTs) procedures. Here, we investigated the relationship between sperm head morphology at high magnification, based on strict morphologic criteria, and the nuclear architecture analyzed by fluorescence in situ hybridization (FISH). We included five men. Two of them had an elevated high-magnification morphology score of 6 points (Score 6) indicating high fertility potential, whereas three had a low score of 0 points (Score 0), indicating low fertility potential. We used FISH to study the inter-telomeric distance and the chromosomal territory area of chromosome 1 (Chr. 1). We then compared these two parameters between subjects with high and low scores. FISH data analysis showed that the inter-telomeric distance (ITD) and chromosomal territory area (CTA) of Chr. 1 were significantly higher in subjects with low scores (score 0) than high scores (score 6). Our results suggest that (i) there is a link between nuclear architecture and sperm head abnormalities, particularly vacuoles; and (ii) it is possible to select spermatozoa with normal nuclear architecture, which might indirectly explain the positive ART outcomes observed with this technique.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted-prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted is known for their relative chemosensitivity and indolent clinical course among diffuse gliomas of adult type. Based on the data from phase 3 clinical trials, the standard of post-surgical care for those tumors is considered to be initial chemoradiotherapy regardless of histopathological grade, particularly with PCV. However, partly due to its renewed definition in late years, prognostic factors in patients with those tumors are not well established. Moreover, the survival rate declines over 15 years, with only a 37% OS rate at 20 years for grade 3 tumors, even with the current standard of care. Given that most of this disease occurs in young or middle-aged adults, further improvements in treatment and management are necessary. Here, we discuss prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy in those tumors.

[Prenatal diagnosis of a fetus with 1p36 deletion syndrome and 3p26.3p25.2 duplication].

OBJECTIVE: To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication. METHODS: A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People's Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. RESULTS: Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46,XX,t(1;3)(p36.22;p25.2), and the result of FISH was t(1;3)(3pter+,1qter+;1pter+,3qter+). The fetus was found to have a karyotype of 46,X?,add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46,X?,der(1)t(1;3)(p36.22;p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome. CONCLUSION: The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.

Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain.

BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022. RESULTS: The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS. CONCLUSION: Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.