A feasibility study of [18F] FDG PET/CT radiomics in predicting high-risk cytogenetic abnormalities in multiple myeloma

We aimed to investigate the feasibility of predicting high-risk cytogenetic abnormalities (HRCAs) in patients with multiple myeloma (MM) using a spinal MRI-based radiomics method. In this retrospective study, we analyzed the radiomic features of 248 lesions (HRCA [n = 111] and non-HRCA [n = 137]) using T1WI, T2WI, and fat suppression T2WI. To construct the radiomics model, the top nine most frequent radiomic features were selected using logistic regression (LR) machine-learning processes. A combined LR model incorporating radiomic features and basic clinical characteristics (age and sex) was also built. Fivefold external cross-validation was performed, and a comparative analysis of 10 random fivefold cross-validation sets was used to verify result stability. Model performance was compared by plotting receiver operating characteristic curves and the area under the curve (AUC). Comparable AUC values were observed between the radiomics model and the combined model in validation cohorts (AUC: 0.863 vs. 0.870, respectively, p = 0.206). The radiomics model had an AUC of 0.863, with a sensitivity of 0.789, a specificity of 0.787, a positive predictive value of 0.753, a negative predictive value of 0.824, and an accuracy of 0.788 in the validation cohort, which were comparable with the performance in the training cohorts. Radiomic features of routine spinal MRI reflect differences between HRCAs and non-HRCAs in patients with MM. This MRI-based radiomics model might be a useful and independent tool to predict HRCAs in patients MM.

Incidence and Prognostic Significance of High-Risk Cytogenetically Abnormalities in Multiple Myeloma Patients in Colombia

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q remains elusive, many genes at the 1q21 locus have been proposed to cause early progression and resistance to anti-myeloma therapy. The plethora of potential drivers suggests that +1q is not only a causative factor or poor outcomes in MM but may be targetable and/or predictive of response to novel therapies. This review will summarize our current understanding of the pathogenesis of +1q in plasma cell neoplasms, the impact of 1q copy number, identify potential genetic drivers of poor outcomes within this subset, and attempt to clarify its clinical significance and implications for the management of patients with multiple myeloma.

The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges

Context Multiple myeloma (MM) is a malignancy of the bone marrow characterized by the abnormal growth of plasma cells. It represents 1% of all malignancies and 10% of hematological malignancies. These proliferating plasma cells produce monoclonal immunoglobulins (M-protein, M component, paraprotein) and lead to symptoms such as kidney issues, high calcium levels, bone fractures, bone marrow problems, and thickened blood due to suppression of normal immunoglobulins. Traditional methods struggle to detect cytogenetic abnormalities in MM due to the low proliferative activity of malignant plasma cells and limited plasma cells numbers in bone marrow samples. However, Microarray-based technologies offer more accurate detection of specific target arrangements as well as chromosomal copy number changes. Aims The objective of this study is to identify oncogene dysregulation in MM by gene expression profiling using DNA microarray technology. Settings and design Traditional methods struggle to detect cytogenetic abnormalities in MM due to the low proliferative activity of malignant plasma cells and limited plasma cells numbers in bone marrow samples. However, microarray-based technologies offer more accurate detection of specific target arrangements as well as chromosomal copy number changes. Methods and patient The study involved 20 clinically diagnosed MM patients at the Oncology department in Beni-Suef University hospitals. DNA microarray technique was used to detect different gene dysregulation in MM patients. Results Show that gain in 14q32.33 is the most common genetic change, present in 90% of MM patients. Other genetic gains include changes in regions such as 8p11.22, 2p11.2, 3q26.1, 20p13, and 22q11.22, found in varying percentages of patients. 14q32.33 gain is the most frequent as it was present in 18 (90%) of MM patients. Other gains include 8p11.22, 2p11.2, 3q26.1, 20p13, 22q11.22 and 6p22.3 present in 35, 30, 10, 10, and 5% of MM patients, respectively. Loss in 11q11 is the most frequent genetic loss, occurring in 15% of MM patients. Other losses include changes in regions like 4q13.3, 5p15.33, 8p23.1, 12q15, 12q23.2, 8q12.2, 13q32.3, and 20p13, present in 10, 10, 10, 10, 10, 5, 5, and 5% of MM patients respectively. Conclusion 14q32.33 gain is the most common genetic change, as it was present in 18 (90%) of MM patients, while 11q11 loss is the most common as it was present in three (15%) of MM patients in this sample from Egypt.

This study examines the impact of cytogenetic abnormalities and their co-segregation on the prognosis of newly diagnosed multiple myeloma patients. The analysis included 1304 patients from four different GEM-PETHEMA clinical trials. Genetic alterations, such as t(4;14), t(14;16), del(17p), +1q, and del(1p), were investigated using FISH on CD38 purified plasma cells. The frequency of genetic alterations detected were as follows: del(17p) in 8%, t(4;14) in 12%, t(14;16) in 3%, +1q in 43%, and del(1p) in 8%. The median follow-up was 61 months, and the median progression-free survival (PFS) and overall survival (OS) were 44 months and not reached, respectively. Consistent with previous reports, the presence of t(4;14) was associated with shorter PFS and OS. In our series, the presence of t(14;16) did not impact survival, maybe due to limitations in sample size. Del(17p) was linked to poor prognosis using a cut-off level of ≥20% positive cells, without any impact of higher cut-off in prognosis, except for patients with clonal fraction ≥80% who had a dismal outcome. Cosegregation of cytogenetic abnormalities patients worsened the prognosis in t(4;14) patients but not in patients with del(17p), which retained its adverse prognosis even as a solitary abnormality. Gain(1q) was associated with significantly shorter PFS and OS, while del(1p) affected PFS but not OS. Nevertheless, when co-segregation was eliminated, the detrimental effect of +1q or del(1p) was no longer observed. In conclusion, this study confirms the prognostic significance of high-risk cytogenetic abnormalities in MM and highlights the importance of considering co-occurrence for accurate prognosis assessment.

Background & Objective:Cytogenetic abnormalities in Multiple myeloma (MM) has emerged as the most important factor that determine the prognosis and survival. Fluorescence in situ hybridization (FISH) can detect a greater number of cytogenetic abnormalities as compared to conventional karyotyping and hence has become the standard test in determining genetic abnormalities in MM. The present study was planned as there is an unmet need to find out various cytogenetic abnormalities and to implement them in prognostic stratification by Revised International Staging System (R-ISS) among Indian population.Methods:A single institution retrospective study was conducted among a total of 117 patients newly diagnosed as Multiple Myeloma. They were analyzed for various cytogenetic abnormalities by using interphase FISH (iFISH) and were staged according to Revised International Staging System (R- ISS).Results:Out of the 117 patients studied, deletion 17p13 (p53) was present in 16 patients (13.67%). Thirty patients (25.64%) showed deletion 13q14.3. Three patients (2.56%) were detected to have t(4:14).Two patients (1.7%) had t(11:14) and t(14:16), respectively. Total of 19 patients (16.23%) in our study exhibited high risk cytogenetics and two among them had more than one high risk cytogenetic abnormalities. There was a 66.4% moderate correlation between ISS-III and high-risk cytogenetics which was statistically insignificant. Of the total 117 patients, 37 (31.62%) were staged R-ISS III.Conclusion:High risk cytogenetics was found in 16.23 % of our study population and del 17p13 was the most common high-risk cytogenetic abnormality. Of the studied subjects, 31.62% had R-ISS III, which is significantly higher compared to western population.

Prognostic Impact of Hyperdiploidy on Multiple Myeloma in the Era of New Agents

Impact of Multiple High-Risk Cytogenetic Abnormalities on the Survival Outcomes of Patients with Primary Plasma Cell Leukemia

Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

Impact of Deletion 17p On the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Age 40 Years and Under Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transmplant

Prognostic Relevance of Clonal Circulating Plasma Cells Detected By Multiparameter Flow Cytometry in Patients with Newly Diagnosed Multiple Myeloma Treated with Novel Agents: Comparative Investigation with the Revised International Staging System

Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

7571 Background: Cytogenetic abnormalities in multiple myeloma (MM) highly influence the disease course, response to treatment and survival. Trisomies and immunoglobulin H chain translocations are primary CA while del(17p), gain(1q), del(1p) among others are secondary CA. Gain (3 copies) and amplification (>3 copies) 1q have been recognized as adverse prognostic markers and incorporated into the second revision of the International Staging System (R2-ISS). However, the role of del(1p) is less well defined, especially in the era of novel therapies. We aimed to analyze the outcomes of newly diagnosed MM (NDMM) patients with chromosome 1 abnormalities, mainly del 1p, treated with autologous stem cell transplant (ASCT) consolidation at our institution. Methods: We conducted a retrospective study of all NDMM patients who were treated with ASCT from 1/1/2015-2/13/2019 (n=511). High-risk cytogenetics (HRC) were defined by the presence of del(17p), t(4;14), or t(14;16) similar to R-ISS; standard-risk cytogenetics (SRC) were defined as the absence of HRC. Modified HR cytogenetics (mHRC) included gain/amp 1q and/or t(14;20) in addition to HRC, while ultra high-risk (uHRC) included 2 or more mHRC CA. Results: Of 511 pts transplanted, 453 had cytogenetic data at the time of diagnosis. SRC were seen in 353 pts (77.9%), while 100 (22.1%) had HRC, 156 (34.4%) had mHRC, and 43 (9.5%) had uHRC. Thirty-two (7.1%) pts had del(1p) while 105 (23.2%) had gain 1q and 30 (6.6%) had amplification 1q. As expected, compared to SRC pts, pts with HRC, mHRC and uHRC had higher risk of relapse or death. Patients with gain and amp 1q had inferior outcomes in terms of progression-free survival (PFS) (HR 1.35; 95% CI 1.06-1.73, p=0.016), time to next treatment (TTNT) (HR 1.84; 95% CI 1.40-2.42, p<0.001) and overall survival (OS) (HR 1.47; 95% CI 1.06-2.02, p=0.02) compared to those without, consistent with published literature. The median PFS, TTNT and OS from ASCT in pts with gain/amp 1q were 3.17 years (y), 3.95y and 7.13y, respectively, compared to 4.01y, 7.60y and 8.21y in pts without gain/amp 1q. Pts with del(1p) had inferior PFS (median 2.43y versus 3.98y; HR 1.75; 95% CI 1.16-2.64, p=0.008), TTNT (median 2.72y versus 6.17y; HR 1.96; 95% CI 1.22-3.14, p=0.005) and OS (median 4.11y versus 8.38y; HR 2.19; 95% CI 1.34-3.58, p=0.002) from the time of ASCT compared to those without del(1p). Conclusions: In our study of NDMM patients that underwent AHCT, del(1p) at diagnosis was an independent predictor of shorter PFS, TTNT and OS. Despite induction therapy involving novel drugs and ASCT consolidation, patients with del(1p) at diagnosis continue to have inferior outcomes. Larger analyses are needed to validate the prognostic value of del(1p) and investigate its role in predicting outcomes in MM.