Multiple Myeloma Patients Research Articles

Real-world comparison of adherence to branded 20 mg dexamethasone tablets and generic 4 mg dexamethasone tablets among patients with multiple myeloma.

e19518 Background: Branded 20 mg dexamethasone tablets (BDex) is the first and only FDA-approved dexamethasone specifically indicated for the treatment of adult patients with multiple myeloma (MM) in combination with other anti-myeloma products. Generic oral dexamethasone is only available at lower dosages (e.g., 4 mg) despite the standard dexamethasone dosage for MM being 20 or 40 mg. The availability of 20 mg tablets would, therefore, reduce pill burden and assumably improve adherence in MM patients. The objective of this analysis was to quantify and compare adherence of BDex and generic 4 mg dexamethasone (GDex) among MM patients using real-world evidence. Methods: Using an open claims database, which included professional, hospital, and pharmacy claims for over 295 million individuals across the United States from 2015 to 2023, BDex and GDex users aged ≥18 years with MM were identified. Baseline summary statistics were generated and chi-squared and t-tests were performed comparing continuous and categorical variables respectively between the treatment cohorts. Treatment adherence was determined using a medication possession ratio for flexible time period (MPRF) given variable numbers of cycles across patients. MPRF was reported as both a continuous and binary measure (≥80%). Differences in MPRF were determined utilizing t-tests. Results: Between September 1, 2020 and June 30, 2023, 43 BDex and 3,775 GDex users meeting all study criteria, including ≥2 prescription claims, were identified. Overall, 30.8% were aged 18-64 years, 54.6% were male, 71.2% were insured through Medicare, and 20.3% were insured commercially. Bortezomib monotherapy, immunomodulatory agent monotherapy, and daratumumab and bortezomib were the most common treatment regimens (17.5%, 11.1%, 7.2%, respectively). Mean MPRF was significantly higher in BDex users compared to GDex overall (97.1% vs 89.5%, p <0.001), among those 18-64 (98.7% vs 89.1%, p <0.001), those with commercial insurance (99.9% vs 90.4%, p<0.001), and those with Medicare (96.1% vs 89.6%, p=0.048). A significantly greater proportion of BDex users were considered adherent compared to GDex patients (95.3% vs 78.4%, p=0.007). This trend was seen across age and payer sub-cohorts, with significant differences seen in those with Medicare (96.0% vs 78.7%, p= 0.035). Conclusions: Adherence to BDex was greater than to GDex in this MM study population overall, and for age group and payer sub-cohorts. Given these findings, physicians may want to consider overall pill burden and regimen complexity when prescribing MM treatment for their patients.

Comparison of peripheral blood automated hematopoietic progenitor cell count and flow cytometric CD34+ cell count.

Stem cell apheresis in the context of autologous stem cell transplantation requires an accurate cluster of differentiantion 34 (CD34+) count determined by flow cytometry as the current gold standard. Since flow cytometry is a personnel and time-intensive diagnostic tool, automated stem cell enumeration may provide a promising alternative. Hence, this study aimed to compare automated hematopoietic progenitor enumeration carried out on a Sysmex XN-20 module compared with conventional flow cytometric measurements. One hundred forty-three blood samples from 41 patients were included in this study. Correlation between the two methods was calculated over all samples, depending on leukocyte count and diagnosis. Overall, we found a high degree of correlation (r = 0.884). Furthermore, correlation was not impaired by elevated leukocyte counts (>10 000/μL, r = 0.860 vs <10 000/μL, r = 0.849; >20 000/μL, r = 0.843 vs <20 000/μL, r = 0.875). However, correlation was significantly impaired in patients with multiple myeloma (multiple myeloma r = 0.840 vs nonmyeloma r = 0.934). Stem cell measurement carried out on the Sysmex XN-20 module provides a significant correlation with flow cytometry and might be implemented in clinical practice. In clinical decision-making, there was discrepancy of under 15% of cases. In multiple myeloma patients, XN-20 should be used with caution.

Evaluation of interleukin-18 levels in patients affected by multiple myeloma and monoclonal gammopathy of undetermined significance: analysis and review of the literature.

Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

A potential best-in-class BCMA-CD19 bispecific CART with advanced safety by self-inhibiting IFNG signaling during CRS.

2502 Background: CART cells have demonstrated remarkable clinical efficacy in treating hematological cancers. However, CRS remains as a major challenge in clinical application, with multiple cytokines significantly elevated. IL6 signaling blockade by Tocilizumab has become a standard treatment to relieve CRS in patients. Our previous studies suggested that CAR T secreting IL6 antagonist could effectively maintain IL6 at very low levels during CRS. Furthermore, we observed that a huge quantity of tumor cells in one patient was significantly reduced after CART infusion, but a low level of IFNG with only grade 2 CRS was present. Therefore, we hypothesized that high level of IFNG might not be necessary to CART clinical efficacy and direct blockade of IFNG signaling by CART secreting an IFNG antagonist (designated as SAFET) serves an interesting approach to effectively reduce CRS toxicity. Although IFNG is usually thought important in T cell cytotoxicity, our results indicated that IFNG KO or autonomous secretion of IFNG antagonist did not affect the killing activity of CART cells. Methods: This pilot phase 1 study of SAFET BCMA/CD19 BiCART self-inhibiting IFNG signaling is a single arm study conducted in China, enrolling refractory/relapsed multiple myeloma patients. The patients had received more than 3 lines of prior therapies including at least a proteasome inhibitor and an immunomodulatory agent and were refractory to the last line of treatment. Lymphodepletion was performed with fludarabine and cyclophosphamide prior to the CART infusion. Following 2-14 days of rest, patients received a single infusion of SAFET BCMA/CD19 BiCART, at the dose of 0.4-1.0 × 108 CAR+ T cells/patient. The primary objectives of this study were to evaluate the safety and efficacy of SAFET BCMA/CD19 BiCART. The pharmacokinetics of SAFET BCMA/CD19 BiCART was investigated by quantitative PCR based detection of CAR vector copies in peripheral blood. Minimal residual disease (MRD) negativity was assessed by standardized multicolor flow cytometry analysis of bone marrow aspirate. Results: 10/11 R/R MM patients achieved CR and 1 achieved VGPR. Among the 10 CR patients, 7 remained CR after treatment with a median PFS 858 days; 1 patient showed relapse at Days 215; 2 patients showed MRD positive relapse at Days 637 and 733, and then received KRd and/or Kd treatment to achieve SD and MRD negative CR. Interestingly, the remarkable short and long term remission suggested that CART self-inhibiting IFNG signaling did not impair the CART clinical efficacy. Notably, minimal CRS was observed, including 6 grade 0, 2 grade 1, 2 grade 2, and 1 grade 3 who displayed mild transient hypotension for only 1 day while there were 79.5% blast tumor cells in the bone marrow before CART therapy. Conclusions: These results suggest BCMA-CD19 bispecific CART self-inhibiting IFNG signaling is promising in translation to a best-in-class treatment for MM. Clinical trial information: ChiCTR2000032124.

Real world outcomes of high dose melphalan conditioning prior to autologous stem cell transplant in extramedullary multiple myeloma vs. multiple myeloma without extramedullary involvement: A single center experience.

7550 Background: Extramedullary multiple myeloma (EMM) is defined as the presence of multiple myeloma plasma cells, which develop outside of the bone marrow. It is an aggressive form of multiple myeloma that is associated with a poor prognosis. The current standard of care for multiple myeloma consists of induction, high dose melphalan autologous stem cell transplant (ASCT), followed by maintenance. However, there is limited data on the outcome of patients with extramedullary multiple myeloma who undergo ASCT. Therefore, we examined the outcomes of high dose melphalan conditioning prior to ASCT in EMM patients compared to multiple myeloma patients without extramedullary involvement (non-EMM) at an academic institution in Los Angeles. Methods: We retrospectively reviewed 246 multiple myeloma patients who underwent ASCT after receiving high dose melphalan conditioning at USC Norris Comprehensive Cancer Center from Jan 2017 to Dec 2022. The cohort was subdivided into 70 EMM patients and 176 non-EMM patients. Outcomes were measured as the status of disease response, which was evaluated at 100 days (D+100) and 365 days (D+365) after the date of transplant. Results: In the EMM group, 1.43% (n=1) was found to have progression at D+100 and 12.86% (n=9) at D+365. In the non-EMM group, 0.57% (n=1) was found to have progression at D+100 and 11.93% (n=21) at D+365. There was no statistical significance between the EMM and non-EMM groups for progression free survival at D+100 (p-0.50) and D+365 (p-0.75). Regarding overall survival, there were 0 deaths observed at D+100 in both the EMM and non-EMM groups. For D+365, the overall survival was 98.57% (n=69) for the EMM group and 99.43% (n=175) for the non-EMM group. There was no statistical significance between the overall survival at D+365 (p-0.14). Conclusions: The EMM cohort exhibited similar rates of progression free survival (87.14% vs. 88.07%) and overall survival (98.57% vs. 99.43%) compared to the non-EMM cohort at one year post ASCT after receiving high dose melphalan conditioning. We observed that there was no significant statistical difference between the EMM and non-EMM cohorts regarding progression-free survival (p-0.75) and overall survival (p-0.14) on day 365. According to our data, high dose melphalan conditioning prior to autologous stem cell transplant is equally as effective for patients with multiple myeloma with or without extramedullary involvement. Future studies with long-term follow-up are recommended to further explore these findings. [Table: see text]

Hospitalization risk in multiple myeloma episodes of care.

e23101 Background: The Enhancing Oncology Model (EOM) is a total cost of care (TCOC) program that was initiated in July 2023. Participating groups are expected to reduce expenditures while delivering high-quality care. Hospitalization (IP) is an important quality metric and cost driver in TCOC programs such as EOM. Understanding how cancer treatment may impact IP is essential for success. Multiple Myeloma (MM) treatment has transformed with multi-agent treatment as the standard of care (SOC), routinely incorporating 3 or more drugs used concurrently to maximize response. We examined the impact multi-drug treatment had on IP rates in MM patients. Methods: Using Parts A, B and D Medicare claims data from EOM baseline period (January 2019 - June 2022) for 12 participating practices, we extracted a unique count of chemotherapy drugs and IP admissions attributed to 6-month episodes of care. Dexamethasone (dex) was included even if claims were not found. Planned and cancer-surgery related IP were excluded using the Clinical Classifications Software Planned Admission Procedure Categories and per EOM specifications. IPs were dichotomized as Yes/No. A logistic regression model was developed to evaluate the association between the number of unique drugs and the unplanned IP, adjusting for variables: prior chemo, age at episode start, race, and HCC count. A 3-drug regimen was established as the reference (including dex) based on SOC. Results: 11,613 episodes had a primary diagnosis of MM, with at least one IP occurring in 2,382 episodes. The number of episodes (% IP) per drug count group are 1-2: 6636(16.3%); 3: 3772 (23.6%); 4: 863 (30.8%); 5+: 342 (40.9%). Detailed statistics are provided in Table 1. Compared to a 3-drug regimen, 4+ drugs increased the risk of IP, while episodes with 1-2 drugs had a lower risk of IP after adjusting for age, race, HCC count and prior treatment. Conclusions: Our findings can guide the design of care transforming interventions aimed at avoiding unnecessary IP while using guideline concordant SOC treatments for MM, driving TCOC reduction. Identifying patients with a higher likelihood of IP helps practices target patient monitoring programs. To understand why patients with prior treatment had lower IP identifying maintenance following initial treatment and patients receiving 3 or more drugs after failure of prior therapy, are worth exploring further. CMMI Disclaimer: The statements contained in this document are solely those of the authors and do not necessarily reflect the views or policies of CMS. The authors assume responsibility for the accuracy and completeness of the information contained in this document. [Table: see text]

Impact of multiple myeloma on outcomes of acute myocardial infarction: A propensity score matched analysis.

e24027 Background: Patients with multiple myeloma (MM) are at increased risk of cardiovascular events secondary to its complications and adverse effects of pharmacotherapy. However, data on in-hospital outcomes of MM on acute myocardial infarction (AMI) is limited due to the clinical scenario being relatively uncommon. Thus, we conducted a retrospective study to investigate the in-hospital outcomes and resource utilization of AMI admissions in MM patients. Methods: We extracted data from the National Inpatient Sample (NIS) Database from 2016 to 2020. We included all admissions ≥18 years old with a principal diagnosis of AMI with and without co-morbid MM using International Classification of Diseases Tenth Revision (ICD-10) codes. Propensity score matching was performed to balance hospital characteristics, patient demographics and comorbidities between the two groups. Univariate logistic regression was performed in the balanced cohorts. The primary outcome was inpatient mortality. Analysis was performed using STATA-MP, version 14.2. Results: A total of 3,191,049 hospitalizations for AMI were identified between 2016 and 2020, of which 6,565 (0.21%) had co-morbid MM. After propensity score matching, compared to those without MM, admissions for AMI with MM had higher odds ratio (OR) of mortality (OR 1.51, 95% CI 1.1-2.08, p = 0.01). Similar rates of complications such as respiratory failure, cardiogenic shock, stroke and vascular complications were seen between the two cohorts. However, acute kidney injury was more common in patients with MM (OR 1.81, 95% CI 1.52-2.14, p &lt; 0.01). Compared to those without MM, admissions for AMI with MM were less likely to undergo coronary angiogram (OR 0.73, 95% 0.63-0.86, p &lt; 0.01), percutaneous coronary intervention (PCI) (OR 0.71, 95% CI 0.60-0.84, p &lt; 0.01) or coronary artery bypass grafting (CABG) (OR 0.52, 95% CI 0.37-0.71, p &lt; 0.01). There was no difference in the length of stay but median hospitalization charges were higher in the cohort with MM ($ 54,125 vs $ 58,493, p &lt; 0.01). Conclusions: Despite similar complication rates, patients with multiple myeloma (MM) who presented with acute myocardial infarction (AMI) experienced higher in-hospital mortality compared to those without MM. One plausible explanation is that patients with MM were less likely to undergo definitive management procedures such as coronary angiogram, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) during their admission, as observed in our study. Alternatively, MM might independently predict worse outcomes for AMI. Further research is needed to understand the interplay between AMI and MM, as well as to identify factors contributing to disparities in outcomes and intervention rates between patients with and without MM.

Efficacy of a Daltuzumab-containing Regimen in Patients with mSMART High-Risk Multiple Myeloma

To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Patient-reported treatment-related symptoms and use of the PRO-CTCAE for multiple myeloma clinical trials: A qualitative interview study.

e19516 Background: Therapeutic regimens for multiple myeloma (MM) involve multiple pharmacological agents, including steroids. Many cause treatment-related symptoms that add to patient burden or may trigger treatment cessation. This study gathered qualitative data about the patient experience with MM treatments, including regimens with steroids. Findings were summarized and compared to the Patient Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), to assess its comprehensiveness and relevance in MM clinical trials. Methods: Individual, semi-structured interviews were conducted virtually with a diverse sample of 16 US-based, English-speaking adults (38% male, 25% Black, 13% Hispanic) to explore their experiences with MM and treatments, including perspectives on steroids and potential benefits of steroid-sparing regimens. Content analysis was used to summarize and compare terminology participants used to describe their experiences with treatments. Results: Participants reported a diverse set of treatment-related symptoms impacting their overall experience, indicating the importance of assessing regimen tolerability in clinical trials. Steroids were linked to increased energy that interfered with sleep or functioning, irritability, taste changes, weight gain, increased appetite, and cognitive symptoms like brain fog. Participants reported that most symptoms were tolerable, but they would prefer to avoid steroids if treatment benefits did not diminish. Many reported symptoms were included in the PRO-CTCAE items (see Table), but several symptoms related to regimens with steroids are not covered: excess energy, bitter/metallic taste, taste sensitivity, brittle nails, irritability, hunger/increased appetite, and muscle weakness. Conclusions: MM patients experience a range of treatment-related symptoms, many of which impact their quality of life. If given the option, patients would prefer a steroid-free regimen if there was proven clinical benefit. While the PRO-CTCAE covers most of the treatment-related symptoms, proving to be an option for multiple myeloma clinical trials, additional PRO instruments may be needed to cover specific gaps in the PRO-CTCAE item library content coverage. [Table: see text]

Bone Metabolism of Multiple Myeloma Bone Disease Patients with Different Blood Separation Results

To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma (MM) bone disease (MBD) patients with different blood separation results. A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group [119 cases, serum, colloid and red blood cell (RBC) from top to bottom of sample] and abnormal group (15 cases, serum, mixed layer of RBC and serum, colloid and RBC from top to bottom of sample) according to the results of blood separation. According to the imaging findings, MBD was classified into grade 0-4, grade 0-2 was mild, and grade 3-4 was severe. The MBD grade of patients in the two groups was analyzed. The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated. The correlation between β2-microglobulin (MG) and bone metabolic indexes was analyzed by Pearson correlation analysis. In the control group, there were 69 cases of grade 0-2 and 50 cases of grade 3-4, while in the abnormal group, there were 5 cases of grade 0-2 and 10 cases of grade 3-4, the difference was statistically significant (P < 0.05). The serum β2-MG, β-CTX levels in abnormal group were both significantly higher than those in control group, while the levels of P1NP and osteocalcin (OC) were significantly lower (all P < 0.001). In the control group, there were 95 patients with ≥ partial response (PR) and the blood separation results were not changed, while 24 patients with <PR and 5 of them had abnormal blood separation results. In the abnormal group, 9 patients with efficacy ≥PR showed normal blood separation results, while 6 patients with efficacy < PR and 5 of them still remained abnormal blood separation results. Compared with before treatment, β-CTX and β2-MG of patients with efficacy ≥PR were significantly decreased but P1NP and OC increased in the control group (all P < 0.001), which was the same as abnoraml group (both P < 0.001, P < 0.01). There were no significant changes in the levels of all indexes in the two groups of patients with efficacy < PR (P >0.05). Compared with before treatment, the levels of β-CTX and β2-MG in the control group with unchanged blood separation results were significantly decreased (both P < 0.001), while the levels of P1NP and OC were significantly increased (P < 0.01, P < 0.001), and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change (P >0.05); the levels of β-CTX and β2-MG in the abnormal group transformed to normal blood separation result were significantly decreased (both P < 0.01), while the levels of P1NP and OC were significantly increased (P < 0.001, P < 0.01), and the level of each index in patients with unchanged blood separation results did not significantly change (P>0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with β-CTX (r =0.709, P < 0.001), and negatively correlated with P1NP and OC (r =-0.410,r =-0.412, both P < 0.001). MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis, which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels, leading to more serious bone metabolic homeostasis disorder. The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition, efficacy monitoring and prognosis evaluation of MBD patients.

The effect of distance reiki on patient reported quality of life, correlated with changes in immune repertoires among patients with multiple myeloma: A pilot study.

e23199 Background: Psychological distress and diminished health related quality of life (HRQOL) is associated with multiple myeloma (MM). Complementary and alternative medicine (CAM) is an adjunct to traditional medicine. T-cells are essential to the adaptive immune system. The complementarity determining region (CDR3) of the T cell receptor formed by combination of the V,D,J regions is highly variable and critical for antigen specificity. PCR is used to analyze the TCR-CDR3 to monitor T-cell clonotypes as a measure of antigen specific T cell responses and thereby cancer immunity. Reiki is a Japanese energy healing technique involving noninvasive light touch to modulate energy fields. The primary aim was feasibility and acceptability of Reiki within a structured medical paradigm. Secondary aims were changes in HRQOL and T-cell receptor repertoires with Reiki. Methods: Adult MM patients (pts) on a stable regimen were eligible. Pts randomized in a 1:1:1 to weekly True Reiki (Treiki), Simulated Reiki (Sreiki) or no intervention (NI). The PROMIS-29® assessed HRQOL. A “Was it Worth it” (WIWI) questionnaire was administered post intervention to assess the experience. TCR-CDR3 sequencing was performed on PBMCs at enrollment and end of therapy to determine immune repertoire changes. Samples underwent library preparation and next generation sequencing for TCR repertoire analysis by iRepertoire® Results: Thirty pts were randomized into 3 arms between 12/2020 to 4/2022. Median age 62.5 (range 27-76), 18/30 (60%) female, median time to diagnosis was 48 mo (Range 7-221), 50% had high risk FISH,(90%) had prior ASCT and received median 2 (range 1-13) lines of therapy prior to enrollment. No pts relapsed or progressed during study period. Using WIWI 100% of pts in Treiki and 75% in Sreiki arms found the therapy useful and would do it again; 100% Treiki pts and 87.5% in the Sreiki arm would recommend the study to others. No statistical difference between groups in any HRQOL domains. Among TCR repertoires, no statistically significant difference was observed between groups with respect to Richness, Shannon entropy, Clonality, Diversity 50 (D50) and Inverse Simpson indexes. Each pt showed substantial variability in certain TCR-CDR3 clones and clonal diversity. Conclusions: We successfully demonstrated acceptability and feasibility of Reiki among MM pts, although no impact on HRQOL was shown. Reiki intervention is an easy non-invasive additional option for pts’ to their conventional therapies. The TCR-CDR3 repertoires showed no difference with the reiki intervention but had significant variability. Further research comparing TCR repertoires between MM and age/sex matched healthy controls is ongoing. T-cell directed therapies are evolving in MM, we plan to analyze if changing diversity of TCR-CDR3 repertoires could define how best to sequence these treatments. Clinical trial information: NCT04783038 .

Apixaban versus warfarin for primary thromboprophylaxis in patients with multiple myeloma undergoing immunomodulatory treatment.

7548 Background: Immunomodulatory drugs (IMiDs) have been demonstrated to improve clinical outcomes in patients with multiple myeloma (MM), but are associated with an elevated risk of thromboembolism. Existing guidelines recommend low-dose direct oral anticoagulants as an alternative to warfarin for primary thromboprophylaxis in MM. However, the data comparing these two therapies are limited. We aim to compare the efficacy and safety of apixaban versus warfarin in patients with MM undergoing IMiD treatment. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult patients with MM who underwent IMiD treatment. Patients treated with apixaban were matched in a 1:1 ratio to those treated with warfarin using clinical variables a priori. The primary safety outcomes included all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding, while the primary efficacy outcomes included thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke within a 3-year period following IMiDs initiation. Results: We identified 448 patients on apixaban who were matched to patients on warfarin. In a Cox proportional hazard analysis, apixaban was associated with a 30% lower risk of all-cause mortality compared to warfarin (Hazard ratio (HR), 0.70 [95% CI: 0.56-0.88]).There was a tendency toward a reduced risk of gastrointestinal bleeding in patients treated with apixaban compared to warfarin (HR, 0.58 [95% CI: 0.31-1.08], log-rank p = 0.083). The risk of intracranial hemorrhage was similar between the two groups.The risks of thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke were comparable between the apixaban and warfarin cohorts. Conclusions: Apixaban was associated with a lower risk of all-cause mortality and a comparable risk of bleeding and thromboembolism compared with warfarin among MM patients undergoing immunomodulatory treatment. [Table: see text]

Immunophenotypic Profile and Measurable Residual Disease Monitoring in Multiple Myeloma: A Prospective Study From a Tertiary Care Centre in Southern India.

Multiple myeloma (MM) immunophenotyping (IPT) and measurable residual disease (MRD) monitoring by flow cytometry is a surrogate for progression-free survival and overall survival in clinical trials. However, plasma cell enumeration is challenging owing to morphological discrepancies and plasma cell (PC) loss during the sample processing. In (n=87) newly diagnosed MM patients, we evaluated the immunophenotype of PCs at baseline, and for a subset of 35 patients MRD at post-induction was quantified and analyzed for association with outcomes and survival.The software Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc., Chicago, IL, USA) was used for all the statistical analysis. Immunophenotyping showed strong positive expression of CD56 (83%), CD200 (94%), CD38 (92%), and CD117 (91%) and negative/weak expression of CD19 (83%), CD45 (89%), CD27 (74%), and CD81 (90%) respectively. Negative/weak expression of CD19 was significantly associated with age ≥56 years (p<0.048), with lower albumin (<3.4g/dL, p<0.001). Strong positive CD56 expression was significantly associated with the presence of M-protein (p<0.03). Strong positive CD117 expression was significantly associated with lower albumin (p<0.02). Strong positive CD200 expression was significantly associated with a good response (p<0.02). The median (IQR) value of bone marrow (BM)-MRD% was 0.005 (0.002-0.034). We found that there was no significant difference in the correlation, association, and survival outcomes with MRD%. This study sheds light on the utility of IPT as an invaluable diagnostic tool in disease management. The findings of this study could be important when it comes to modifying the criteria for high-risk diseases and implementing a risk-adapted first therapy in clinical practice.

Real world outcome of patients with multiple myeloma who received bispecific antibodies after CAR-T therapy.

7520 Background: There are 2 CAR-T products and 3 bispecific antibodies (BsAbs) that are FDA-approved for patients (pts) with relapsed, refractory multiple myeloma (MM). Clinical trials experience to date suggests that clinical response of BsAb is less impacted after CAR-T therapy. We examined the outcome of pts who received BsAb in standard-of-care (SOC) practice at Mayo Clinic Rochester. Methods: Retrospective analysis of MM patients who received FDA-approved BsAb at Mayo Clinic, Rochester between 12/2022- 1/2024. IMWG criteria was used for clinical response. Results: Sixty-two patients received BsAbs: 77% (48/62) received teclistamab, and 23% (14/62) received talquetamab. Median age was 62 years (range: 33-81), 60% (37/62) were males, and 45% (28/62) received prior CAR-T. Patients who had prior CAR-T therapy had more prior lines of therapy compared to those who did not. Overall, ORR to teclistamab was 61%, which is comparable to previous studies and other real-world reports. ORR and ≥CR rates were comparable between patients with and without prior CAR-T (Table). Of the 28 pts who received CAR-T before BsAbs, 61% (17/28) received idecabtagene vicleucel, 10% (3/28) were ciltacabtagene autoleucel, and 29% (8/28) on clinical trial. We then compared outcome of BsAb between pts who had relapsed from CAR-T within 1 year (n=21, median PFS: 8.84 months (range, 1.12, 10.84)) or after 1 year (n=7, median PFS: 16.62 months (range, 13.30, 36.20)). At the time of BsAb infusion, pts with who relapsed &lt; 1 year vs ≥1 year post CAR-T had comparable blood counts, ALC, M-protein and involved FLC levels, CRP, ferritin and LDH. BsAb CR/sCR rate was significantly higher in pts with disease relapse ≥1 year compared to &lt;1 year post CAR-T (57% vs 14%, p=0.02). Conclusions: Irrespective of prior CAR-T exposure, BsAb have clinical activity in SOC practice in pts with MM. Our preliminary data suggest that responses to BsAbs are better in pts with late compared to early relapse post CAR-T. Longer follow-up is needed to understand the duration of response. Larger, multi-center studies with longer follow-up will help identify factors that impact BsAb response post CAR-T.[Table: see text]

Multiple myeloma in the African American population: A 2010-2020 NCDB analysis.

e19531 Background: Multiple myeloma (MM) exhibits a disproportionately higher prevalence among African American individuals. Various factors contribute to the disease's progression, severity, and prognosis. This analysis presents real-world data from the National Cancer Database (NCDB) from 2010 to 2020. Methods: Cohort of 241,446 MM patients between 2010 and 2020 were analyzed. Demographic variations, including age, gender, insurance status, educational attainment, and median household income, were examined. Multivariate Cox regression analysis was conducted to identify factors influencing survival outcomes. Results: Within the database, from 2010 to 2020, 51,668 cases of multiple myeloma were recorded among Black individuals. The age group most affected was 40 to 65 years (50.2%), followed by those over 65 (47.3%), with 2.5% falling between 18 to 40 years, and a mean age of 64.4 years. Most cases affected females (51.5%), with most households earning less than $40,227 annually. A significant portion of Black patients did not receive a transplant (83.8%) or immune based option (73.1%). The mean duration from diagnosis to therapy initiation was 37.5 days. Multivariate analysis revealed that patients over 65 had a worse prognosis (HR = 1.52, 95% CI: 1.47 – 1.57, P &lt; 0.001) compared to those under 65, while females exhibited a better prognosis (HR = 0.88, 95% CI: 0.86 – 0.91, P &lt; 0.001). Patients with private insurance had better outcomes (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001), as did those treated in academic centers (HR = 0.89, 95% CI: 0.87 – 0.92, P &lt; 0.001). Additionally, patients receiving any form of transplant had better outcomes (HR = 0.45, 95% CI: 0.42 - 0.49, P &lt; 0.001), along with those undergoing chemotherapy (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001) and immunotherapy (HR = 0.67, 95% CI: 0.64 – 0.69, P &lt; 0.001). Conclusions: The analysis highlights significant demographic and treatment influences among African American patients with MM. Some identifiable factors associated with improved outcomes include younger age, female gender, private insurance, treatment in academic centers, and most importantly receipt of transplant and Immunotherapy. These findings underscore the importance of targeted interventions considering various factors and improving outcomes in this population. [Table: see text]

From criteria to clinic: How updated SLiM CRAB criteria influence multiple myeloma diagnostic activity.

7556 Background: Multiple myeloma (MM) is a plasma cell malignancy, which is preceded by asymptomatic, precursor state of monoclonal gammopathy of undetermined significance (MGUS). Once diagnosed with MGUS, monitoring for progression to MM is recommended. The diagnostic criteria for active MM include presence of ≥1 CRAB features (hypercalcemia, renal failure, anemia, or one or more osteolytic bone lesions on skeletal radiology, CT or PET/CT imaging) in addition to clonal plasma cells on bone marrow. In 2014, the International Myeloma Working Group (IMWG) added SLiM to the criteria: clonal bone marrow plasma cells ≥60%, serum free light chain (FLC) ratio ≥100, and &gt;1 focal lesion on magnetic resonance imaging (MRI). This study investigated the longitudinal influence of the updated diagnostic criteria on the utilization of imaging examination and the number of MM diagnoses overtime among patients with MGUS. Methods: We used data from the U.S. Veterans Health Administration (VHA) 2010-18. Patients with MGUS were identified by a published natural language processing (NLP) model. MM cases diagnosed under the old criteria were identified using International Classification of Diseases (ICD)-9/10 codes for CRAB symptoms, while cases diagnosed under the new criteria were identified using a published NLP-assisted model developed based on the SLiM-CRAB criteria. We then performed a counterfactual comparison to contrast the number of MM cases that would have been diagnosed under the old criteria with those under the new criteria. To monitor changes in the use of advanced imaging technology, we calculated the frequency of imaging examinations orders &lt;1 year following MGUS diagnosis, including whole-body/spine computed tomography (CT), MRI and positron emission tomography-CT. Results: A total of 29,336 MGUS patients were identified. MGUS patients undergoing whole-body or spine MRI/CT scans &lt;1 year following-MGUS diagnosis increased from 15.72% during 2010-13 to 21.06% during 2015-18 ( P = 0.002). In 2010-13, 346 MM cases were diagnosed per year on average with the old criteria. This number increased to 666 cases in 2015-18 with the updated criteria. Had the new criteria been applied retrospectively to 2010-13, the number of diagnoses would have increased 28% (to 441 cases per year). Conversely, had the old criteria been applied to 2015-18, the number of diagnoses would have decreased by 29% (to 473 cases per year). Conclusions: Our study revealed a significant increase in MM diagnoses after adding the SLiM biomarkers into the updated diagnostic criteria. In parallel, there has been an increase in the use of CT/MRI imaging for MGUS patients, suggesting a shift towards more aggressive diagnostic strategies. Further analysis is warranted to evaluate the positive detection rate of active MM through imaging and to understand the implications of early detection on MM patient outcomes.

Efficacy of carfilzomib-based regimens as induction/consolidation therapy in newly diagnosed multiple myeloma: A meta-analysis.

e19535 Background: Carfilzomib (K) is a 2nd generation selective and irreversible proteosome inhibitor. It has shown encouraging results in newly diagnosed multiple myeloma (NDMM) patients. However, no direct comparisons were made among different regimens. This analysis aims to compare efficacy with different K-based regimens in NDMM. Methods: A literature search was done on PubMed and Embase with keywords for “Carfilzomib” and “multiple myeloma” till 1/1/2024. 25 articles (N = 3221) were included after screening 2800 articles. Data was collected for overall response rate (ORR), complete response (CR), minimal residual disease negativity (MRD-), 2-year progression free survival (PFS), and 2-year overall survival (OS). Survival data was extracted from visualization of Kaplan-Meier curve if not provided in text. R software was used for the meta-analysis. Results: In one trial (N = 72), ORR and CR were 90% and 7%, respectively in patients with K and dexamethasone (d). In one trial (N = 111), ORR, CR, PFS, and OS were 93%, 18%, 74%, and 96%, respectively with Kd and thalidomide (T). In six trials (N = 844), ORR, CR, MRD-, PFS, and OS were 92%, 43%, 38%, 78%, and 88%, respectively with Kd and lenalidomide (R). In one trial (N = 22), ORR, CR, and MRD-, were 100%, 64%, and 23%, respectively with Kd and Bendamustine (B). In three trials (N = 576), ORR, CR, MRD-, PFS, and OS were 82%, 23%, 16%, 48%, and 82%, respectively with Kd, and melphalan (M). In three trials (N = 189), ORR, CR, MRD-, PFS, and OS were 89%, 24%, 30%, 71%, and 89%, respectively with Kd and cyclophosphamide (Cy). In two trials (N = 63), ORR, CR, MRD-, PFS, and OS were 97%, 86%, 55%, 95%, and 100%, respectively with KRd and daratumumab (D). In one trial (N = 64), ORR, CR, PFS, and OS were 91%, 8%, 77%, and 95%, respectively with KCyTd. In one trial (N = 46), ORR, CR, MRD-, PFS, and OS were 96%, 70%, 65%, 80%, and 89%, respectively with KRd and elotuzumab (E). In one trial (N = 125), ORR, CR, MRD-, PFS, and OS were 94%, 70%, 79%, 70%, and 78%, respectively with KRd and isatuximab (I). In one trial (N = 526), ORR, CR, MRD-, and PFS were 90%, 18%, 17%, and 78%, respectively with KCyRd. In three trials (N = 280), ORR, CR, MRD-, PFS, and OS were 97%, 66%, 60%, 87%, and 94%, respectively with KRd and stem cell transplant (SCT). In two trials (N = 180), ORR, CR, MRD-, PFS, and OS were 91%, 55%, 43%, 70%, and 85%, respectively with KCyd-SCT. In one trial (N = 123), ORR, CR, MRD-, PFS, and OS were 98%, 86%, 80%, 87%, and 94%, respectively with KRDd-SCT. Conclusions: Among K based regimens, the highest response and 2-year-survival rates were achieved with KRDd, IKRd and were comparable to regimens with SCT. Highest MRD negativity was achieved with KRDd-SCT and IKRd. Hence, four drug regimens can be considered in NDMM to achieve high response and survival rates instead of SCT especially in patients who cannot tolerate or chose not to undergo SCT. Long-term results are needed to confirm these results.

Clinical outcomes and resource utilization in patients with multiple myeloma admitted with gastrointestinal bleeding.

e19522 Background: In multiple myeloma (MM) patients, GIB can be due to factors such as abnormal proteins affecting the GI tract, coagulation issues, or secondary conditions like amyloidosis. There's limited scientific evidence examining outcomes among patients presenting with both GIB and MM. Thus, our objective was to assess clinical outcomes in this specific population. Methods: We accessed the National Inpatient Sample from 2017-2020 to identify adult patients with MM hospitalized due to GIB. The primary endpoint was inpatient mortality, with secondary endpoints including length of stay and total hospital charges. We utilized multivariable logistic regression analysis to estimate clinical outcomes, considering a significance threshold of P &lt; 0.05. Results: We identified 4,067,364 hospitalizations with GIB, among which 22,000 (5.9%) presented with MM. Comparing MM and Non-MM cohorts, the mean age was 71.9 vs 67.8 years, males constituted 58% vs 52.2%, and White ethnicity accounted for 55.6% vs 66.1%. The prevalence of obesity was 10.6% vs 14.5%, diabetes mellitus was 32.1% vs 33.8%, chronic obstructive pulmonary disease was 16.9% vs 20.4%, dyslipidemia was 38.5% vs 40.7%, atrial fibrillation was 27.7% vs 25.6%, hypertension was 22.9% vs 34.7%, heart failure (HF) was 30.7% vs 26.4%, peripheral vascular disease (PVD) was 2.9% vs 4.1%, acute kidney injury was 45.6% vs 29.4%, anemia was 26.3% vs 27.7% and chronic kidney disease (CKD) was 51.9% vs 28.6%. Clinical outcomes revealed stark differences between MM and Non-MM cohorts: in-hospital mortality rates were 10.9% vs 6.3% with an odds ratio (OR) of 1.5 (CI 1.4-1.7); LOS was 9.6 days vs 6.7 days (IRR 1.26, CI 1.21-1.32); and hospital charges were $30,006 vs $20,172 (IRR 1.34, CI 1.26-1.42). All data demonstrated a p-value &lt; 0.001 and were adjusted for various factors including age, sex, race, comorbidity indices, obesity, atrial fibrillation, diabetes mellitus, hypertension, peripheral vascular disease, acute kidney injury, chronic kidney disease, nicotine and alcohol use, stroke, acute respiratory failure, and inflation during 2017-2020. Conclusions: Patients hospitalized for GIB and MM were comparatively older, with a larger male population and fewer Caucasians. They exhibited higher Afib, HF, AKI, and CKD rates with lower occurrences of obesity, DM, COPD, dyslipidemia, HTN, anemia and PVD. This group showed a significantly worse mortality rate with prolonged hospital stays and resource utilization. This entails to have prompt medical attention, appropriate management of bleeding, and addressing the underlying causes are crucial in improving outcomes and reducing mortality rates. Treatment strategies often involve a multidisciplinary approach involving oncologists, hematologists, gastroenterologists, and other specialists to provide comprehensive care tailored to the individual's condition.

The effect of care team-patient relationship on decision-making in relapsed/refractory multiple myeloma.

e19530 Background: Understanding patient involvement in shared decision making is critical for informed decision-making for relapsed/refractory multiple myeloma (RRMM) patients. This study explored the relationships between care teams and patients, who patients talk to and quantify the level of involvement, satisfaction, and comfort in the process of reaching a final change in treatment decision. Methods: HealthTree Cure Hub (PMID: 35271305) was used to conduct a survey for RRMM patients for their first change of therapy decision. Five-point Likert scales were used (1-Not at All Influential to 5-Extremely Influential; 1-Very Satisfied to 5-Very Dissatisfied), along with dichotomous and categorical choices. Results: 294 patients with RRMM were included with a mean age of 66±9, 53% were female, and 49% had graduate level education. Of 219 demographics respondents, 91% were white. Of the people patients talked to, the most influential individuals ranked by somewhat to extremely influential were: 1) myeloma specialist (84%), 2) community hematologist/oncologist (69%), and 3) spouse, partner or significant other (56%). Additionally, 67% of patients talked with nurses, PAs, or RNAs, with 49% finding them somewhat to extremely influential. Seeking a second opinion from a myeloma specialist was reported by 34% of patients and 50% of patients reported talking to other patients about treatment decisions. Patients varied in their description of their relationship/communication approach with their doctor: the doctor makes recommendations, the patients ask questions and they discuss preferences, then 1) patient proposes ideas and the decision is made together (37%), 2) then the patient makes the final decisions (21%) and 3) then the patient follows the doctor’s suggestions (14%). Importantly, a weak positive relationship existed between these levels of patient involvement in the treatment decisions and their involvement-satisfaction in choosing a treatment (r = 0.251, p &lt; 0.001). About half of patients (51%) followed their care team recommendations without changes, while 31% opted for significant alterations, and 19% chose a modified option. Most patients reported making the final decision (59%), followed by their doctor (40%), and the minority reported a caregiver or partner (1%). Conclusions: This study identified that about half of patients engage in a collaborative and active decision-making process, which was related to their involvement-satisfaction of the treatment decision. Patients actively engaged with various individuals, including myeloma specialists, community hematologists/oncologists, and spouse/partners. Notably, discussions with nurses, PAs, and RNAs played a significant role, along with interactions with peers. Taken together a multifaceted engagement highlights the active role of patients in determining their treatment paths within a complex healthcare network.

Clinical Significance of Serum ADA Combined with GLB, CREA, β2-MG and HGB in Newly Diagnosed Multiple Myeloma

To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), β2-microglobulin (β2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM. A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA. ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and β2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), β2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and β2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased β2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, β2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide. The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, β2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.