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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 β‐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. [ABSTRACT FROM AUTHOR]

Objective: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). Methods: This is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle. Results: Twenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better. Conclusions: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase. [ABSTRACT FROM AUTHOR]

Objective: Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence‐based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). Methods: In this open‐label, non‐interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. Results: Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression‐free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised‐International Staging System (R‐ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% (p = 0.036) and SUVmax of PET‐CT scan >4.2 (p = 0.000) were closely correlated with OS in the elderly MM. Conclusions: For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment. [ABSTRACT FROM AUTHOR]

Background: Chidamide is subtype-selective histone deacetylase (HDAC) inhibitor that showed promising result in clinical trials to improve prognosis of angioimmunoblastic T-cell lymphoma (AITL) patients. However, in real world settings, contradictory reports existed as to whether chidamide improve overall survival (OS). Therefore, we aimed to develop an interpretable machine learning (Machine learning)-based model to predict the 2-year overall survival of AITL patients based on chidamide usage and baseline features., Methods: A total of 183 patients with AITL were randomly divided into training set and testing set. We used 5 ML algorithms to build predictive models. Recursive feature elimination (RFE) method was used to filter for the most important features. The ML models were interpreted and the relevance of the selected features was determined using the Shapley additive explanations (SHAP) method and the local interpretable model-agnostic explanationalgorithm., Results: A total of 183 patients with newly diagnosed AITL from 2012 to 2022 from 3 centers in China were enrolled in our study. Seventy-one patients were dead within 2 years after diagnosis. Five ML algorithms were built based on chidamide usage and 16 baseline features to predict 2-year OS. Catboost model presented to be the best predictive model. After RFE screening, 12 variables demonstrated the best performance (AUC = 0.8651). Using chidamide ranked third among all the variables that correlated with 2-year OS., Conclusion: This study demonstrated that the Catboost model with 12 variables could effectively predict the 2-year OS of AITL patients. Combining chidamide in the treatment therapy was positively correlated with longer OS of AITL patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Xu, Gu, Tang, Tang, Wang, Liu, Yang, Zhong and Xu.)

Objective: To assess the status and severity of bone disease in patients with multiple myeloma (MM) by using chest computerized tomography (CT) and the relationship between clinical prognostic parameters and bone disease., Methods: All 46 newly diagnosed MM in-patients received both imaging tests of chest CT and plain X ray. An experienced radiologist reviewed all the imaging data. Clinical laboratory parameters, stages of Durie-Salmon (DS) and International Staging System (ISS) were evaluated. Five cytogenetic abnormalities of bone marrow myeloma cells were tested by fluorescence in situ hybridization (FISH)., Results: The sensitivity of CT and X ray to determine pathological fractures was comparable, the positive rates of which were 41.3% (19/46) and 30.4% (14/46) respectively (P = 0.29). Nevertheless, the positive rate of osteolytic lesions ascertained by CT was significantly higher than that by X ray (P < 0.001), 60.9% (28/46) vs 13.0% (6/46) with diameter 5-10 mm and 50.0% (23/46) vs 10.9% (5/46) with diameter more than 10 mm. Osteolytic lesion numbers found by CT were more than those by X ray [5(0-21) vs 0(0-4) lesions with diameter 5-10 mm (P < 0.001), 2(0-14) vs 0(0-2) lesions with diameter more than 10 mm (P < 0.001), respectively]. Patients with positive osteolytic lesions had higher percentage of RB1 gene deletion [46.7% (14/30) vs 18.8% (3/16), P < 0.001], D13s319 deletion [43.3% (13/30) vs 18.8% (3/16), P < 0.001] and high risk cytogenetic abnormalities [50.0% (15/30) vs 25.0% (4/16), P < 0.001]., Conclusions: Chest CT is more sensitive than plain X ray in detecting osteolytic myeloma bone disease. Osteolysis determined by CT is relevant to clinical DS stages and risk stratification of cytogenetic abnormalities.

Objective: To explore the clinical characteristics of multiple myeloma (MM) patients with overall survival (OS) less than 24 months so as to stratify high-risk population., Methods: A total of 177 newly diagnosed MM inpatients were recruited from July 2008 to July 2012. Clinical parameters at diagnosis of international staging system (ISS), lactic dehydrogenase (LDH), serum calcium, extramedullary involvement and amyloidosis were collected and cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH). Response and death were recorded as endpoints. Otherwise the follow-up period was over 24 months., Results: And 73 patients dying within 24 months were classified into high-risk group while another 104 survivors for over 24 months into control group. Age and gender at baseline were comparable. However, OS of high-risk group was only 8 months while it was not attained during a median follow up of 38 months in control group (P < 0.001). The most common cause of death was progressive disease in both groups. The pre-treatment percentages of the following parameters were significantly higher in high-risk group, including ISS stage III (76.71% (56/73) vs 50.00% (52/104), P = 0.002), renal dysfunction (47.95% (35/73) vs 31.73% (33/104), P = 0.029), elevated LDH (20.55% (15/73) vs 7.69% (8/104), P = 0.015) and plasma cell leukemia (PCL, 5.48% (4/73) vs 0 (0/104), P = 0.016). Conversely, extramedullary involvement, plasmacytoma, amyloidosis and hypercalcemia were similar. Despite comparable chemotherapeutic regimens, the rate of deep response, including complete response (CR) and very good partial response (VGPR), was significant lower in high-risk group than that in control group (12.33% (9/73) vs 53.85% (56/104), P < 0.001). Overall response rates (ORR, i.e. CR+VGPR+ partial response (PR)) were markedly different (38.36% (28/73) vs 86.54% (90/104), P < 0.001). Univariate analysis of cytogenetic abnormalities indicated a higher proportion of 1q21 amplification in high-risk group (35.62% (26/73) vs 25.15% (22/104), P = 0.033). Multivariate Logistic regression revealed that ISS, LDH and primary response worse than PR independently affected early death (P = 0.046, 0.005, < 0.001)., Conclusions: MM patients with OS less than 24 months have distinct clinical characteristics. And aggressive regimens are needed to improve the outcomes of high-risk population.