Fonseca, Rodrigo

Abstract Multiple myeloma (MM) with t(11;14)(CCND1;IGH) remains the only subset sensitive to the BCL2 inhibitor venetoclax. However, not all patients with t(11;14)(CCND1;IGH) respond to treatment, and some progress early after initial response. To investigate this, we examined 44 whole-genome and whole-exome sequencing data samples from 34 patients with t(11;14) MM treated with venetoclax. The presence of mutations in the RAS pathway was strongly associated with shortened progression-free survival (PFS) and was validated in an independent cohort of 21 patients with MM. The presence of 1q gain was also associated with shorter PFS in patients without RAS mutations. In 10 patients with paired prevenetoclax and postvenetoclax treatment samples, postvenetoclax progression was recurrently driven by the selection of genomic events in the BCL2/MCL1 and RAS pathways and of high-risk features (eg, loss of TP53 and CDKN2C). Overall, our study shows that comprehensive genomic profiling can identify most mechanisms underlying resistance to BCL2 inhibition in t(11;14)(CCND1;IGH) MM.

Abstract Introduction: Lisocabtagene maraleucel (liso-cel) was approved in the United States for the treatment of CLL in 3/2024 for patients who have received two prior lines of therapy including a covalent BTK inhibitor and a BCL-2 inhibitor. Data regarding outcomes of liso-cel is limited to reports from the registrational TRANSCEND-CLL 004 clinical trial which had strict inclusion and exclusion criteria. This work investigates the real-world efficacy and safety of liso-cel for patients with CLL and its efficacy in specific sub-populations. Methods: This is a multi-institutional retrospective study (Collaborative Assessment of Real-World Evidence of Lisocabtagene Maraleucel in Patients with Relapsed/Refractory CLL/SLL [CARE CAR-T CLL]) of patients with CLL who received commercial liso-cel in the United States. Patients with Richter transformation were excluded. Response was defined by iwCLL criteria. Patients who did not undergo a marrow biopsy but met other criteria for a complete response (CR) were categorized as unconfirmed CR (CRu). CRS and ICANS were graded per ASTCT criteria. Results: A total of 30 patients were identified with a median age of 67 years (range 44 – 80). Twenty of thirty patients (67%) had either del17p and/or mutated TP53, and 8/30 (27%) had complex karyotype (≥ 3 abnormalities) at time of liso-cel infusion. Patients received a median of 6 prior lines of therapy (range 1 - 12), and 24 (80%) were previously treated with chemotherapy. All patients had previous exposure to a covalent BTK inhibitor and a BCL-2 inhibitor. Twenty-seven (90%) of patients had prior exposure to pirtobrutinib. Twenty-nine patients (96.7%) received bridging treatment that was stopped after leukapheresis with 1 patient in CR and 25 patients in PR at time of liso-cel. Eighteen patients (60%) were treated with pirtobrutinib as the last line of treatment prior to liso-cel. Median length of time on pirtobrutinib prior to liso-cel infusion was 4 months (interquartile range [IQR], 2 – 8 months). Twelve (66.7%) patients stopped pirtobrutinib between leukapheresis and lymphodepletion, and 6 continued after liso-cel. Best CR/CRu rate was 60.0% (CR, n = 17/30; CRu, n = 1/30), and best overall response rate (ORR) was 83.3% (25/30) with median time to best response of 30 days (IQR, 28 – 30 days). Of the 18 patients who received pirtobrutinib as their last line of therapy, 13 (72%) achieved a CR/CRu. Meanwhile, of the 12 patients who did not receive pirtobrutinib as their last line of therapy, only 5 (28%) achieved a CR. Measurable residual disease testing (MRD) by flow cytometry was done in 14/30 patients, and 9 patients (64%) had achieved undetectable MRD (uMRD). MRD by next generation sequencing (NGS) was done in 17 patients, and 7 (41%) patients had uMRD. Twenty-seven of 30 patients (90%) were alive at time of data collection. Median follow-up was 3.3 months (IQR, 1.2 – 8.9 months). Twenty-six patients (87%) experienced any grade cytokine release syndrome (CRS), and 3 patients experienced grade 3 CRS (10%). Twelve patients (40%) experienced any grade immune effector cell-associated neurotoxicity syndrome (ICANS), and 4 patients (13%) experienced grade 3 ICANS. There were no grade 4 or 5 CRS or ICANS. One patient experienced grade 3 immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). At day 30, patients had a median absolute neutrophil count of 1.7K/μL (IQR, 0.8 – 3.6K/μL), hemoglobin of 11.7 g/dL (IQR, 8.6 – 13.1 g/dL), and platelet count of 72K/μL (IQR, 29 – 119K/μL). Conclusion: Real-world analysis of liso-cel for patients with relapsed/refractory CLL showed CR and ORR of 60.0% and 83.3%, respectively. Despite having a heavily pre-treated and chemotherapy-exposed population and with over half the patients having high-risk features, these response rates are higher than what was described in the TRANSCEND-CLL 004 clinical trial. These results are limited by the short follow-up period and the variability in response assessment typical of a retrospective study. As we increase our sample size, we will also be interested if the use of the non-covalent BTK inhibitor pirtobrutinib prior to liso-cel is associated with a higher CR rate, mimicking the findings of the sub-cohort analysis of TRANSCEND-CLL 004 where the concurrent use of ibrutinib led to higher CR rates. Further updates and patients from additional collaborators will be presented at the meeting.

Abstract INTRODUCTION Bispecific antibodies (BsAbs) have emerged as transformative therapies for hematologic malignancies, with several agents now approved for relapsed/refractory acute lymphoblastic leukemia (ALL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL). These therapies have demonstrated remarkable overall response rates across multiple clinical trials, with some now being evaluated in frontline settings. Recent publications have raised concerns about SPMs following CAR-T cell therapy, with the FDA requiring boxed warnings after reports indicated SPMs rates of up to 5%. However, the incidence of SPMs with BsAbs remains poorly characterized, despite shared mechanisms of T-cell activation. METHODS We conducted a systematic literature search via PubMed to identify peer-reviewed publications reporting clinical trials of FDA-approved BsAbs for hematological malignancies. Included agents were blinatumomab (CD19×CD3), glofitamab, mosunetuzumab, epcoritamab, and odronextamab (all CD20×CD3), as well as elranatamab, teclistamab, and linvoseltamab (BCMA×CD3), and talquetamab (GPRC5DxCD3). Eligible studies included phase I-III trials evaluating BsAbs either as monotherapy or combination therapy, irrespective of prior lines of treatment. Studies published only as abstracts were excluded due to insufficient adverse event reporting. Trials were screened for documentation of SPMs, both from main and supplemental publications. Trials were categorized based on SPMs reporting: “N/A” (insufficient data), “No” (explicit acknowledgment of no SPMs or comprehensive AEs reports with no malignancy entries), and “Yes” (direct reporting of SPMs). Only patients who received BsAbs were included in pooled analyses; comparator or control arms from randomized trials were excluded. For trials reporting patient numbers, median follow-up and SPM counts, we calculated crude incidence rates and cumulative incidence per 100 person-years using estimated total person-years. RESULTS We identified 19 clinical trials encompassing 5,133 patients across ALL (n=5 trials), MM (n=4), and NHL (n=10, including DLBCL and follicular lymphoma). Phase distribution included 5 phase 3 trials and 14 phase 1/2 trials. Most trials (n=16, 84%) evaluated BsAbs as monotherapy. The median number of patients enrolled per trial was 145 (range 54-718; mean 193), with a median follow-up of 14.3 months (range 4.2-43 months; mean 18.3). Four trials (21%) had insufficient adverse event data and were excluded from the analysis. The final pooled cohort analysis included 3,215 patients with available long-term safety data and a cumulative follow-up of 6,270 person-years. Across this cohort, 5 SPMs were reported, corresponding to a crude incidence of 0.16% and a cumulative incidence rate of 0.08 per 100-person years. These included 3 cases reported under “neoplasms benign, malignant and unspecified” in the TOWER trial (1 extramedullary leukemic infiltration, 1 pulmonary leukemic infiltration and 1 acute lymphocytic leukemia), along with 1 lung malignancy and 1 case of Hodgkin's lymphoma both from mosunetuzumab studies. CONCLUSION This analysis suggests a low incidence of SPMs with BsAb therapy compared to CAR-T therapy and appears consistent with expected baseline rates in heavily pretreated hematologic malignancy populations. Notably, some reported cases may represent disease progression rather than true SPMs. However, limited follow-up duration across trials warrants continued long-term surveillance, particularly as agents move to frontline settings where longer survival may reveal delayed malignancies.

732 Background: Ampullary carcinoma (AC) is a rare malignancy arising from the ampulla of Vater which has a more favorable prognosis compared to other pancreatic malignancies. Current guidelines favor surgical resection followed by adjuvant therapy for average risk patients (pts), however the type of regimen as well as other perioperative treatment modalities are still being explored. The objective of this retrospective study aims to provide insight into the management of locoregional disease. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) denoting AC between 2010 to 2024 were searched using Mayo Data Explorer and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) data were collected. Statistical analysis was conducted using SAS version 9.04. Results: A total of 137 pts (62% male, n = 85) were identified with median age 66 years old. Histologic subtypes were 54% pancreatobiliary (44/81), 40% intestinal (32/81), 6% mixed (5/81), with 56 pts unknown. Stages at diagnosis were 81% resectable (111/137), 11% locally advanced (15/137), and 8% metastatic (11/137). Nearly all (93%, n = 103/111) pts with localized disease had resection with a 97% R0 resection rate (100/103). Majority (68%, n = 75/111) of resectable pts had perioperative chemotherapy with 5-FU or gemcitabine-based regimens (24%, n = 18/75 neoadjuvant vs. 76%, n = 57/75 adjuvant). Perioperative chemoradiation was given in 17% (19/111) of pts. At median follow up of 30.5 months, recurrence rates were 40% (41/103), primarily to the liver (18/41). Median recurrence free survival (RFS) was 29.3 months (95% CI 24.7 – NE). Median overall survival (OS) has not been reached. The 5-year RFS and OS rates were 0.37 (95% CI 0.25 - 0.55) and 0.69 (95% CI 0.58 - 0.82), respectively. Univariate analysis showed no difference in OS with the addition of neoadjuvant or adjuvant chemotherapy or chemoradiation. Somatic NGS testing showed pathogenic mutations in 90% of pts (63/70): 57% KRAS (36/63; 44% G12D, 19% G12V, 8% G12C, 8% G12D, 19% others); 13% homologous recombination (HR) (8/63); 6% ERRB2 /Her2 amplification (4/63), and 5% mismatch repair (MMR) (3/63). Conclusions: AC has a favorable prognosis in resectable pts. However, high recurrence rates indicate the need for better systemic therapies and improved selection of pts who would benefit from these treatments. Future research should focus on refining perioperative strategies to enhance outcomes and reduce recurrence.

INTRODUCTION Atrial fibrillation (AFib) is a recognized complication in patients with chronic lymphocytic leukemia (CLL) treated with Bruton tyrosine kinase inhibitors (BTKis). Early detection and management of AFib are critical due to its association with increased morbidity and mortality. Traditional detection methods, such as intermittent EKGs and wearable devices, often capture only brief snapshots of cardiac activity, potentially missing episodes. Recent advances in artificial intelligence (AI) have enabled the development of algorithms that analyze electrocardiograms (EKGs) to predict AFib risk. These algorithms can potentially identify patients with undetected AFib and assess risk at a single point, reducing the need for continuous monitoring. This study evaluates the utility of an AI-enabled EKG algorithm in predicting AFib in patients with CLL treated with ibrutinib and acalabrutinib. METHODS Patients with CLL treated with ibrutinib and acalabrutinib were identified from a single-center database. Patients with CLL who received BTKi therapy at Mayo Clinic between 2015 and 2024 with available EKGs in the EMR were included. Patients were excluded if they received BTKi for non-CLL indications or if patients with CLL had documented AFib without accompanying EKGs in their medical records. An AI-enabled EKG algorithm developed by Attia et al. (Lancet, 2019) was used to estimate AFib probability (AFibAI). EKGs were categorized into pre-treatment, during treatment, and post-treatment phases. Mean values of all EKGs within each phase were used for analysis to reduce heterogeneity. Paired t-test was used for continuous variables and ROC analysis was used to evaluate diagnostic performance. A p-value of <0.05 was used for statistical analysis. RESULTS The analysis included 383 individual CLL patients (74% male, median age71; ace/ethnicity not available), of which 79 were treated with acalabrutinib and 304 with ibrutinib, with a total of 5844 EKGs analyzed. The AFibAI was significantly higher in EKGs with documented AFib compared to other EKGs, mostly normal sinus rhythm (0.5710 vs. 0.1857, p <0.001). Pre-treatment AFibAI was higher in patients who ultimately developed AFib after starting BTKi treatment compared to those who did not. Mean AFibAI at baseline was 0.2176 for those who developed AFib and 0.0986 for those who did not (p <0.001; difference between means: -0.1191 +/- 0.02005, 95% CI: 0.-0.1585 - 0.0796). Differences of baseline AFibAI were similar when stratified by BTKi. Trends in AFibAI scores indicated a significant increase during and after BTKi treatment in patients who developed AFib, with mean score of 0.2176 at baseline to 0.4064 post-treatment (p<0.001). In patients who did not develop Afib during BTKi therapy, there was minimal increase of AFibAI scores from 0.1041 at baseline to 0.1620 post-treatment (p = 0.0002). The ROC analysis showed an area under the curve of 0.7280 (SE = 0.03911, 95% CI: 0.6514 to 0.8047, p <0.001), indicating fair discriminatory ability. The sensitivity at the optimal threshold (0.1202) was 65.45% and the specificity was 74.59%, with a Youden's Index of 0.4004. To achieve a sensitivity of ≥90% for detecting patients who ultimately develop AFib, a threshold of 0.2368 was established (specificity of 41.82%). DISCUSSION Our study demonstrates the efficacy of an AI-enabled EKG algorithm in estimating atrial fibrillation risk among CLL patients treated with BTKis. We demonstrated that baseline AFibAI was notably higher in patients who ultimately developed AFib, suggesting that it could potentially identify patients at elevated risk before the onset of AFib. Early identification would allow for closer monitoring and timely intervention, potentially mitigating complications. Pending validation with an external cohort, the 90% sensitivity threshold could help identify the patients at highest risk, where other treatment options could be considered. The trend across different treatment phases revealed a significant increase in scores during treatment, indicating that AFibAI is responsive to changes induced by BTKi therapy and suggest its utility for patient monitoring. Practical questions remain about its impact on clinical decision-making and management. Future prospective studies should confirm the validity of identifying high-risk patients and its role in both treatment decisions and patient outcomes.

Introduction: Multiple myeloma (MM) with t(11;14)(q13;q32), resulting in CCND1;IGH rearrangement, remains the only subset amenable to targeted therapy with the BCL2 inhibitor, Venetoclax. Nevertheless, not all patients with this translocation respond to treatment and some progress early after initial response. The mechanisms behind this clinical heterogeneity are largely unknown. Methods: To investigate mechanisms of heterogeneity in response to Venetoclax, we interrogated 44 whole genome sequencing (WGS) and 24 whole exome sequencing data from a training cohort including 33 patients with t(11;14) MM treated with Venetoclax at the Mayo Clinic. In a validation cohort, we extracted single nucleotide variants (SNV) and indels from 17 MM patients with t(11;14) with available RNAseq data treated with Venetoclax at Emory University. Results: In the training cohort the median number of lines of therapy was 4 and Venetoclax drug regimens included combinations with dexamethasone, proteasome inhibitors, anti-CD38 agents, and immunomodulatory agents. After a median follow up of 30 months, the median progression free survival (PFS) was 9 months, and 13 patients (39%) achieved a complete remission (CR) to therapy, while 9 (27%) were refractory (i.e. no response or progressed within the first 60 days). For our driver discovery analysis, we integrated SNV, indels, copy number variants (CNV) and structural variants (SV). Deletion 17p (del17p) or TP53 mutation, MCL1 gain/amp, and hyper-APOBEC did not correlate with PFS in our cohort (p=0.59, p=0.71, and p=0.05, respectively). In contrast, mutations involving the MAPK pathway (NRAS, KRAS, BRAF, FGFR3) displayed the strongest association with short PFS, which was retained after adjusting for del17p/TP53 mutations, and 1q gain/amp (HR: 4.76, CI: 1.8-12.9, p=0.002). The association between suboptimal response and resistance to Venetoclax in MM patients with MAPK pathway mutations (n=7) was also observed in our validation cohort from Emory University (p=0.046). This is in line with what has been reported in functional studies in acute myeloid leukemia, where RAS pathway promotes MCL1 under the selective pressure of Venetoclax (Zhang et al. Signal Transduct Target Ther 2022). While MAPK mutations explained most cases of refractory patients (86%), the mechanisms through which initially responding patients subsequently progressed remain unclear. To investigate this, we interrogated 10 patients with pre- and post-treatment samples collected at disease progression (PD). We identified genomic events acquired/selected at PD of genes involved in the anti-apoptotic MCL1/BCL2 and MAPK pathways in 6/10 cases. One patient was refractory to Venetoclax and had double minutes involving BCL2, which caused multiple focal amplifications (>30 copies), likely reflecting extrachromosomal DNA. Another patient progressed with an acquired, focal deletion on BCL2L11. In two patients, the progressing clones harbored mutations in MAPK pathways (one BRAF and the other WNK2). Two patients who relapsed after sustained CR had major branching evolution where a previously undetectable focal deletion of PMAIP1 (NOXA) was seen at PD. Importantly, one of these deletions was a biallelic event. Venetoclax sensitivity assays conducted on PMAIP1 knockout in the MM t(11;14) cell line, KMS12PE, demonstrated significantly reduced cell death across all drug concentrations (p<0.05), validating the loss of NOXA as a mechanism of resistance to Venetoclax in MM. Finally, similarly with what was previously reported in chronic lymphocyte leukemia treated with Venetoclax (e.g., Herling et al Nat Comm 2018), CDKN2A/B monoallelic and biallelic focal deletions were selected post-Venetoclax, at PD in 4 patients while TP53 SNV/deletions were selected from subclonal to clonal in 2 patients at PD. Conclusion: In this study, we demonstrate that mutations involving the MAPK pathway identify a population of MM patients with t(11;14)(CCND1;IGH) who are unlikely to respond to Venetoclax. We also show that genomic events involving the MAPK and BCL2/MCL1 pathways are primarily responsible for disease progression after initial response. These findings highlight the critical role of comprehensive genomic profiling through WGS in identifying mechanisms of resistance to targeted therapies in MM, aiding patient selection for Venetoclax, and guiding the development of novel drug combinations.

e19008 Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.

Introduction Fluorescent In-Situ Hybridization (FISH) has been an indispensable tool to characterize the cytogenetic landscape of multiple myeloma (MM), mainly for identifying primary abnormalities such as heavy chain gene (IgH) translocations and odd-number chromosome trisomies. These aberrations play a crucial role in risk stratifying the disease given their correlation with disease aggressiveness, treatment response and overall prognosis. High-risk (HR) cytogenetics are identified through the presence of t(14;16), t(14;20) or loss of the p53 gene locus. Less is known about the prognostic implication of secondary abnormalities, in particular gain of 1q21. We aimed to evaluate the association between primary and secondary cytogenetic abnormalities and their impact on overall survival (OS) in MM patients. Methods We performed a retrospective analysis on a FISH records database from three Mayo Clinic campuses. Cohort included patients >18 years of age, diagnosed with multiple myeloma between 2005 and 2022, with FISH performed within two years of diagnosis. Demographics including age, date of diagnoses and OS data were retrieved from electronic medical records. Statistical analyses were done using BlueSky Statistics software. Study was conducted in accordance with the principles of the Declaration of Helsinki; informed consent was obtained from all participants. Results We analyzed a total of 2221 patients, among which 59.8% were male, with a median age of diagnosis 65 years. Hyperdiploidy was the most prevalent primary cytogenetic abnormality observed in 44.3% of patients, followed by t(11;14) as the most common translocation (23%), and t(4;14) (8.2%). Gain(1q21) was assessed in 925 patients, among which 64%, 30.3% and 5.7% had 2, 3 and ≥4 copies respectively. Furthermore, 11.4% (n=253) exhibited either mutated TP53 or del17p, and 37.8% (n=839) presented with 13q loss or monosomy 13. The median follow-up for the overall population was 102 months (8.5 years), with a median OS of 75.5 months. Patients with high-risk translocations had significantly shorter median OS of 40.01 months compared to 80.65 months for those with standard risk translocations (p <0.001). The presence of ≥4 1q copies was associated with significantly reduced overall survival (2 copies: not reached, 3 copies: 69.4 months, ≥4 copies: 40.1774; p <0.001). This was consistent even when considering the presence of high-risk translocations (Figure 1). To confirm the independent significance of these findings, we performed multivariate Cox regression models, incorporating age at diagnosis, year of diagnosis, gender, presence of hyperdiploid disease, and presence of high-risk translocations. Given that overall survival outcomes were analyzed irrespective of treatment received, we incorporated year of diagnosis as a variable to control for potential impact of evolving treatment regimens over the years. The presence of ≥4 1q copies was associated with reduced OS, with a hazard ratio (HR) of 2.12 (CI: 1.38-3.26; p <0.001). The presence of 3 copies also showed prognostic significance (HR: 1.43; p: 0.012). Similarly, both the presence of TP53mut/mon17 (HR: 1.96, CI: 1.66-2.31; p <0.001) and 13qdel/mon13 (HR: 1.21, CI: 1.08-1.38) were associated with decreased OS. On the other hand, 1p deletion did not have any significant prognostic implications (HR: 1.84, CI: 0.38-1.59; p 0.113). When incorporating all cytogenetic events into a multivariate model, variables associated with reduced OS included age at diagnosis, the presence of both of 3 and ≥4 1q copies, TP53mut/mon17, t(4;14), t(14;16) and t(14;20). However, 13qDel/mon13 lost significance when incorporated with other abnormalities (Table 1). Conclusion Our investigation sheds light on the less explored realm of secondary cytogenetic abnormalities and confirm a strong association between increasing number of 1q copies and reduced overall survival, independent of other cytogenetic abnormalities and treatment regimens. These results underscore the utility of FISH-based comprehensive cytogenetic profiling at baseline, which enables reliable identification of high-risk patients. Future prospective trials should further elucidate the pathogenic mechanism for these findings. Our analysis used OS as primary endpoint and included over 2000 MM patients, reinforcing the clinical relevance of our findings.

The Health Level 7 (HL7) organization introduced the Information Sensitivity Policy Value Set with 45 sensitive data categories to facilitate the implementation of granular electronic consent technology. The goal is to allow patients to have control over the sharing of their sensitive medical records. This study represents the first attempt to explore physicians’ viewpoints on these categories. Twelve physicians participated in a survey, leading to revisions in 21 HL7 categories. They later classified 600 clinical data items through a second survey using the updated categories. Participants’ perspectives were documented, and data analysis included descriptive measures and heat maps. In the first survey, six participants suggested adding 19 new categories (e.g., personality disorder), and modifying 25 category definitions. Two new categories and sixteen revised category definitions were incorporated to support more patient-friendly content and inclusive language. Fifteen new category recommendations were addressed through a revision of category definitions (e.g., personality disorder described as a behavioral health condition). In the second survey, data categorizations led to recommendations for more categories from ten participants. Future revisions of the HL7 categories should incorporate physicians’ viewpoints, validate the categories using patient data or/and include patients’ perspectives, and develop patient-centric category specifications.