Explore the vast range of titles available.

Patients with relapsed and refractory multiple myeloma (RRMM) have a poor prognosis and limited treatment options after exposure to an immunomodulatory drug, proteasome inhibitor (PI), and anti-CD38 antibody (triple-class exposure [TCE]). However, current understanding about the management of these patients and associated health care resource use (HCRU) is limited outside the United States. The objective of the International Treatment pattern and resource use Evaluation for Multiple myeloma In a Study of triple-class Exposed patients (ITEMISE) study was to use a physician-developed survey fielded to hematologists across Europe and Canada to assess the treatment, management, HCRU, and end-of-life care for patients with RRMM after TCE. The ITEMISE study used a 3-phase Delphi-like approach that consisted of in-depth interviews with 7 hematology experts; the development of a cross-sectional survey fielded to hematologists across Belgium, Canada, France, Germany, Italy, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom from August to October 2020; and a final workshop of hematology experts to validate the pooled findings. Hematologists were asked to consider the management of patients in the first 3 treatment lines after TCE, including treatment options, treatment duration and outcomes, and frequency of outpatient visits and hospitalizations. The survey was completed by 202 hematologists (60% from academic hospitals, 38% from other public hospitals, and 2% from private hospitals). Hematologists estimated that 55% of patients would receive active treatment after TCE, the equivalent of fourth-line treatment onward since diagnosis of multiple myeloma. Immunomodulatory drug, anti-CD38 antibody plus immunomodulatory drug, and PI-based regimens (received by 22.5%, 17.8%, and 15.1% of patients, respectively) were reported for first treatment strategy after TCE. Pomalidomide, daratumumab, lenalidomide, bortezomib, and carfilzomib were the most frequently selected antimyeloma agents. Associated outcomes of median overall survival, progression-free survival, and objective response rate for first treatment after TCE were estimated as 12 months, 4 months, and 40%, respectively. HCRU included outpatient visits and unplanned hospitalizations that were commonly reported during treatment after TCE. Findings indicate an intent to actively treat patients after TCE with a range of combination regimens frequently consisting of immunomodulatory drugs, PIs, and anti-CD38 antibodies, highlighting the lack of standard of care and suggesting a large clinical unmet need. Estimated clinical outcomes are consistent with data from US studies and indicate the poor prognosis for patients after TCE. Substantial HCRU is associated with management of patients after TCE across Europe and Canada, signifying a high patient and societal impact and a need for better treatment options to reduce this burden.

Background In the phase 2 KarMMa trial, patients with relapsed/refractory multiple myeloma (RRMM) achieved deep and durable responses with idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy. Here we report a sub-analysis of the Japanese cohort of KarMMa. Methods Adult patients with RRMM who had received  ≥ 3 prior treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and had disease refractory to last treatment received ide-cel at a target dose of 450 × 10 6 CAR positive T cells. Results Nine patients were treated with ide-cel. The overall response rate was 89% (median follow-up, 12.9 months). The best overall response was stringent complete response in 5 patients (56%), very good partial response in 3 (33%), and stable disease in 1. Median duration of response was not reached. All patients experienced grade ≤ 2 cytokine release syndrome and one patient experienced grade 2 neurotoxicity, but all resolved. Two patients died, one each from plasma cell myeloma and general health deterioration. Conclusion Ide-cel yielded deep, durable responses with a tolerable and predictable safety profile in Japanese patients with RRMM. These results are similar to those of the non-Japanese population in KarMMa.

Background Patients with triple class exposed (TCE), relapsed and refractory (RR) multiple myeloma (MM) have limited treatment options and poor prognosis. Elranatamab, a bispecific BCMA-targeted antibody, is an investigational treatment for RRMM with demonstrated efficacy and safety in MagnetisMM-3, a single-arm, multi-centre, phase-2 study. This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to treatments available in routine clinical care for TCE RRMM in the NHS. Methods A retrospective, observational, external control arm (ECA) study combining participants from a single arm, multi-centre phase 2 study, MagnetisMM-3, receiving elranatamab to compare patient characteristics and median survival using a comparator cohort of TCE RRMM patients treated with real world regimens in five UK centres between 2015 and 2023. Both naive and adjusted treatment effect estimates for progression free survival (PFS) and overall survival (OS) were obtained using inverse probability of treatment weighted (IPTW) Cox proportional hazards models and differences in restricted mean survival time (dRMST). Quantitative bias analysis was used to assess the robustness of effect estimates to unmeasured confounding. Results From a total of 5,535 patients identified with a diagnosis of MM, 81 were identified as eligible for inclusion in the ECA. A total of 13 different regimens were recorded as being initiated from the real world RRMM at index date, the most common regimen was pomalidomide + dexamethasone (48.15%). Clinical outcomes in the ECA were poor (median PFS 3.71 months [95% confidence interval (CI) 2.73–4.73], median OS 11.00 months [8.02–18.10]). In unadjusted analyses the elranatamab cohort had significant improvements in PFS (dRMST 6.95 months [4.08–9.61]) and OS (Hazard Ratio (HR) 0.66 [0.45–0.96]). Adjusted analyses showed similar effects for PFS (dRMST 6.45 [3.05–9.45]) but were equivocal for OS (HR 0.75 [0.46–1.26]). Conclusion This study provides recent real world evidence of poor outcomes in TCE RRMM in the UK. PFS was longer among patients who received elranatamab compared with treatments for TCE RRMM in routine UK clinical practice.

Introduction A novel therapy for heavily pretreated triple‐class–exposed multiple myeloma (TCE MM) is B‐cell maturation antigen (BCMA)‐targeted immunotherapy. While the number of TCE+BCMA‐exposed patients is growing, real‐world data for this group are limited. Methods We present real‐world data from patients with TCE+BCMA‐exposed MM who initiated a subsequent line of therapy (LOT) using a US‐based claims database, Komodo's Healthcare Map. Results We identified 656 TCE+BCMA‐exposed patients; mean age was 66.5 years. Time from MM diagnosis to index was 5.4 years; mean number of prior LOTs was 5.9. The most prevalent prior therapy received within each drug class was daratumumab (98.5%), pomalidomide (86.0%), carfilzomib (85.8%) and belantamab mafodotin (74.5%). A total of 137 different subsequent treatment regimens were observed following TCE+BCMA exposure; the most common regimen was teclistamab (10.4%). The top three targeted agents within the subsequent regimen were carfilzomib (20.2%), pomalidomide (20.1%) and bortezomib (16.6%). Among this TCE+BCMA‐exposed population who received subsequent treatment, the median time to next treatment or death was 6.8 (95% CI, 6.1–7.5) months; time to treatment discontinuation or death was 3.5 (95% CI, 3.2–3.7) months. Conclusion This first real‐world analysis of patients with heavily pretreated TCE+BCMA‐exposed MM shows poor clinical outcomes, frequent therapy retreatment and no standard‐of‐care, highlighting the need for novel treatments. Clinical Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Introduction Multiple myeloma (MM) prognosis worsens once patients become triple‐class exposed (TCE) to at least one treatment in each class: immunomodulators, proteasome inhibitors, and anti‐CD38 monoclonal antibodies. Methods We conducted a retrospective study using the Cancer Analysis System database to assess characteristics, treatment patterns, and clinical outcomes for adults diagnosed with MM between 2014 and 2020. The main cohort included patients ≥18 years‐old diagnosed with incident MM (including TCE patients) who had at least one record of systemic anticancer therapy treatment within 30 days prior to, on, or any time after their diagnosis. Results The main cohort comprised 14,990 patients, predominantly white and male, with a median age at diagnosis of 71 years. Of these, 848 (5.6%) became TCE. In the main cohort (n = 14,990), 57.2% of patients received only one line of therapy, and >50% of all first‐line regimens included bortezomib. Median overall survival (OS) from diagnosis was 51.5 months. After becoming TCE (n = 848), median OS was 13.2 months and median time to next treatment or death was 5.7 months. Conclusions This study provides current evidence on real‐world OS and management for patients with MM in England, including those who become TCE.

To estimate the budget impact of adding elranatamab to the US formulary to treat adults with RRMM who have received ≥4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, and to assess the total cost of care and cost per month of progression-free survival (PFS) between elranatamab and available treatments. An economic model was developed to assess the budget impact of elranatamab in a one-million-member US commercial and Medicare health plan. Epidemiology data was obtained from the SEER database and a large US real-world study. Key clinical inputs included treatment duration, PFS, overall survival, and adverse events (AEs). Costs associated with drug acquisition monitoring, medical resource use (specifically hospitalization and physician visits), and AEs were incorporated. Model inputs were sourced from clinical trial data, US government databases, and published literature. Total budget impact and per member per month (PMPM) were assessed. One-way sensitivity analyses (OWSA) were conducted to assess model input uncertainty. Total cost of care and cost per month of PFS were also assessed. An estimated 14 (commercial) and 60 (Medicare) RRMM patients per year would be eligible for treatment. Adding elranatamab resulted in a total budget impact of $553,607 ($0.05 PMPM) in commercial and $2,351,515 ($0.20 PMPM) in Medicare over three years. OWSA indicated results were most sensitive for elranatamab drug costs and relative dose intensity. Total cost of care per month of median PFS over one year was $19,642 with elranatamab, talquetamab ($33,391), teclistamab ($37,791), selinexor plus dexamethasone ($48,784), physician's choice of treatment ($65,886), idecabtagene vicleucel ($78,361), and ciltacabtagene autoleucel ($17,640). Elranatamab for RRMM is projected to result in a minimal to small budget impact over 3 years and good economic value with lower cost of care per month of PFS compared with other available RRMM treatments except for ciltacabtagene autoleucel.

Introduction Ciltacabtagene autoleucel (cilta‐cel) is a novel chimeric antigen receptor T‐cell therapy that is being evaluated in the CARTITUDE‐1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti‐CD38 monoclonal antibody (i.e., triple‐class exposed). Given the absence of a control arm in CARTITUDE‐1, this study assessed the comparative effectiveness of cilta‐cel and physician's choice of treatment (PCT) using an external real‐world control arm from the Flatiron Health multiple myeloma cohort registry. Methods Given the availability of individual patient data for cilta‐cel from CARTITUDE‐1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression‐free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted. Results Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta‐cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; p < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; p < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; p < 0.0001]) versus PCT. Cilta‐cel treatment benefit was robust and consistent across all sensitivity analyses. Conclusion Cilta‐cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple‐class exposed RRMM.

Due to the absence of a head-to-head trial directly comparing elranatamab and teclistamab in triple-class exposed/refractory multiple myeloma (TCE/R MM), a matching-adjusted indirect treatment comparison (MAIC) was previously conducted. The aim of the current study was to update this prior MAIC with more mature clinical data from both trials. The approach of the MAIC remained consistent with the previous study, with the exception of more mature data (28.4 months and 30.4 months of follow-up for elranatamab from MagnetisMM-3 (NCT04649359) and teclistamab from MajesTEC-1 (NCT03145181, NCT04557098), respectively). Individual patient-level data from MagnetisMM-3 (N = 116) were reweighted to match published aggregated data from MajesTEC-1. Variables included for adjustment were age (≥75 years), sex (for OS only), median time since diagnosis, International Staging System disease stage, high-risk cytogenetics, extramedullary disease, number of prior lines of therapy, Eastern Cooperative Oncology Group performance status, and penta-exposed/refractory status. An unanchored MAIC was conducted based on the National Institute for Health and Care Excellence Decision Support Unit 18 example code. A sensitivity analysis was conducted in which missing baseline characteristics data were imputed for elranatamab. In the base-case analysis, elranatamab was associated with significantly longer PFS (hazard ratio [HR] 0.55 [95% confidence intervals (CI): 0.37, 0.81], p < 0.05), OS (HR [95% CI]: 0.60 [0.40, 0.91], p < 0.05, and DoR 0.56 [0.31, 0.99] p < 0.05) compared with teclistamab. Results were largely consistent in the sensitivity analysis, except that the differences in OS were non-significant. A subgroup analysis of patients with a complete response or better was consistent with the base case. The results of this updated MAIC of elranatamab and teclistamab in TCE/R MM support the findings of the previous MAIC over a longer-term follow-up, now indicating significantly improved PFS, OS, and DoR with elranatamab versus teclistamab.

Some patients with multiple myeloma are receiving treatment in clinical practice in England after prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti‐CD38 monoclonal antibody. We investigated the characteristics of these patients, their outcomes, and the salvage therapies they received using the national cancer registry for England and linked healthcare data. After a median follow‐up time of 6.4 months from T0, median overall survival and time to next treatment were 8.2 and 5.3 months, respectively. This real‐world data provide useful clinical insight into a little‐studied patient population and highlight the poor outcomes in the UK setting.