P957: AN INDIRECT COMPARISON OF ELRANATAMAB’S (ELRA) OBJECTIVE RESPONSE RATE (ORR) FROM MAGNETISMM-3 (MM-3) VERSUS REAL-WORLD EXTERNAL CONTROL ARMS IN TRIPLE-CLASS REFRACTORY (TCR) MULTIPLE MYELOMA (MM)
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SUBMITTER: Costa L
PROVIDER: S-EPMC10431376 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician's choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152). Elranatamab was associated with a significantly higher objective response rate (risk ratios, 1.88-2.25), significantly longer progression-free survival (hazard ratios [HRs], 0.37-0.57), and, across most analyses, significantly longer overall survival (HRs, 0.46-0.66) versus PCT. BCMA-naive patients who were treated with elranatamab exhibited significantly better outcomes than patients treated in real-world clinical practice.
| S-EPMC11318743 | biostudies-literature
Project description:BackgroundDespite advances, most patients with multiple myeloma (MM) experience relapse and repeat multiple treatment lines, highlighting an unmet need for patients with relapsed or refractory MM (RRMM). Bispecific antibodies are a new option, but their efficacy and safety in Japanese patients are unknown.MethodsThis was an analysis of Japanese patients receiving elranatamab monotherapy in MagnetisMM-2 (NCT04798586) and MagnetisMM-3 (NCT04649359). Both studies evaluated a priming dose regimen of elranatamab followed by weekly subcutaneous doses, in patients with disease progression while receiving or who were intolerant to ≥3 prior therapies (≥1 proteasome inhibitor, ≥1 immunomodulatory drug and ≥1 anti-CD38 monoclonal antibody). The primary endpoints were dose limiting toxicities (DLTs) in MagnetisMM-2 and confirmed objective response rate (ORR) in MagnetisMM-3. In both, key secondary endpoints included safety, tolerability, duration of response, time to response, progression-free survival and overall survival.ResultsIn MagnetisMM-2 (N = 4) and MagnetisMM-3 (n = 12), median ages were 68.5 and 66.5 years, respectively. No DLTs were observed in MagnetisMM-2. ORRs were 50.0% (95% CI, 6.8-93.2) and 58.3% (95% CI, 27.7-84.8) in MagnetisMM-2 and MagnetisMM-3, respectively. All patients experienced treatment-emergent adverse events in MagnetisMM-2 (grade 3/4: 75.0%) and MagnetisMM-3 (grade 3/4: 100%); cytokine release syndrome occurred in 100% (grade 3/4: 25.0%) and 58.3% (no grade 3/4) of patients, respectively. Neither study reported immune effector cell-associated neurotoxicity syndrome.ConclusionsNo new safety signals were observed, and ORRs were similar to that of the overall MagnetisMM-3 trial population, supporting further studies of elranatamab in Japanese patients with RRMM. ClinicalTrials.gov identifier: NCT04798586 (MagnetisMM-2), NCT04649359 (MagnetisMM-3).
| S-EPMC11374885 | biostudies-literature
Project description:Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete response. Fifty responders switched to biweekly dosing, and 40 (80.0%) improved or maintained their response for ≥6 months. With a median follow-up of 14.7 months, median duration of response, progression-free survival and overall survival (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). With biweekly dosing, grade 3-4 adverse events decreased from 58.6% to 46.6%. Elranatamab induced deep and durable responses with a manageable safety profile. Switching to biweekly dosing may improve long-term safety without compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .
| S-EPMC10504075 | biostudies-literature
Project description:Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy. Primary endpoints, including the incidence of dose-limiting toxicities as well as objective response rate (ORR) and duration of response (DOR), were met. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Eighty-eight patients with relapsed or refractory MM received elranatamab monotherapy, and 55 patients received elranatamab at efficacious doses. Patients had received a median of five prior regimens; 90.9% were triple-class refractory, 29.1% had high cytogenetic risk and 23.6% received prior BCMA-directed therapy. No dose-limiting toxicities were observed during dose escalation. Adverse events included cytopenias and cytokine release syndrome. Exposure was dose proportional. With a median follow-up of 12.0 months, the ORR was 63.6% and 38.2% of patients achieving complete response or better. For responders, the median DOR was 17.1 months. All 13 patients evaluable for minimal residual disease achieved negativity. Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months. Elranatamab achieved durable responses, manageable safety and promising survival for patients with MM. ClinicalTrials.gov Identifier: NCT03269136 .
| S-EPMC10579053 | biostudies-literature
Project description:This study investigated the trajectory-planning problem of a six-axis robotic arm based on deep reinforcement learning. Taking into account several characteristics of robot motion, a multi-objective optimization approach is proposed, which was based on the motivations of deep reinforcement learning and optimal planning. The optimal trajectory was considered with respect to multiple objectives, aiming to minimize factors such as accuracy, energy consumption, and smoothness. The multiple objectives were integrated into the reinforcement learning environment to achieve the desired trajectory. Based on forward and inverse kinematics, the joint angles and Cartesian coordinates were used as the input parameters, while the joint angle estimation served as the output. To enable the environment to rapidly find more-efficient solutions, the decaying episode mechanism was employed throughout the training process. The distribution of the trajectory points was improved in terms of uniformity and smoothness, which greatly contributed to the optimization of the robotic arm's trajectory. The proposed method demonstrated its effectiveness in comparison with the RRT algorithm, as evidenced by the simulations and physical experiments.
| S-EPMC10346668 | biostudies-literature
Project description:PurposeTo study the endoscopic ostium characteristics and outcome of 8 × 8 mm osteotomy in external dacryocystorhinostomy (DCR) using the microdrill system.MethodsThis prospective interventional pilot study was performed on 40 eyes of 40 patients with primary acquired nasolacrimal duct obstruction (NLDO) from June 2021 to September 2021 in patients undergoing external DCR. An 8 × 8 mm osteotomy was performed using round, cutting burr attached to a microdrill system. Success was defined as patent ostium on lacrimal syringing (anatomical) and a Munk score <3 (functional) at 12 months. Postoperative endoscopic ostium evaluation was done using a modified DCR ostium (DOS) scoring system at 12 months.ResultsThe mean age of the study participants was 42.41 ± 11.77 years and the male-to-female ratio was 1:4. The mean duration of surgery was 34.15 ± 1.66 minutes and that for osteotomy creation was 2.5 ± 0.69 minutes. The mean intraoperative blood loss was 83.37 ± 11.89 ml. Anatomical and functional success rates were 95% and 85%, respectively. The mean modified DOS score was "excellent" in 34 patients (85%), "good" in 1 patient (2.5%), "fair" in 4 patients (10%), and "poor" in 1 patient (2.5%). Complications included nasal mucosal injury in 10% (4/40) of patients, complete cicatricial closure of ostium in 2.5% (1/40), incomplete cicatricial closure in 10% (4/40), nasal synechiae in 5% (2/40), and canalicular stenosis in 2.5% (1/40).ConclusionAn 8 × 8 mm-sized osteotomy created by powered drill and covered by lacrimal sac-nasal mucosal flap anastomosis in external DCR is an effective technique that has minimal complications and shorter surgical time.
| S-EPMC10418034 | biostudies-literature
Project description:An external control arm based on health registry data can serve as an alternative comparator in single-arm drug development studies that lack a benchmark for comparison to the experimental treatment. However, accessing such observational healthcare data involves a lengthy and intricate application process, delaying drug approval studies and access to novel treatments. Clinical trials typically comprise only a few hundred patients usually with high-cardinality features, which makes individual data instances more exposed to re-identification attacks. We examine whether synthetic data can serve as a proxy for the empirical control arm data by providing the same research outcomes while reducing the risk of information disclosure. We propose a reversible data generalization procedure to address these particular data characteristics that can be used in conjunction with any generator algorithm. It reduces the input data cardinality pre-synthesis and reverses it post-synthesis to regain the original data structure. Finally, we test a selection of state-of-the-art generators against a suite of utility and privacy metrics. The external control arm benchmark was generated using data from Norwegian health registries. In this retrospective study, we compare various synthetic data generation algorithms in numerical experiments, focusing on the utility of the synthetic data to support the conclusions drawn from the empirical data, and analysing the risk of sensitive information disclosure. Our results indicate that data generalization is advantageous to enhance both data utility and privacy in smaller datasets with high cardinality. Moreover, the generator algorithms demonstrate the ability to generate synthetic data of high utility without compromising the confidentiality of the empirical data. Our finding suggests that synthetic external control arms could serve as a viable alternative to observational data in drug development studies, while reducing the risk of revealing sensitive patient information.
| S-EPMC11756779 | biostudies-literature
Project description:ObjectivesExternal control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs).DesignSystematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality.Data sourcesEmbase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023.Eligibility criteriaEligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator.Data extraction and synthesisTwo authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors.ResultsForty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data.ConclusionsStandardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research.
| S-EPMC10729249 | biostudies-literature
Project description:ObjectivesRandomized controlled trials (RCTs) are the gold standard for evaluating the comparative efficacy and safety of new cancer therapies. However, enrolling patients in control arms of clinical trials can be challenging for rare cancers, particularly in the context of precision oncology and targeted therapies. External Control Arms (ECAs) are a potential solution to address these challenges in clinical research design. We conducted a scoping review to explore the use of ECAs in oncology.MethodsWe systematically searched four databases, namely MEDLINE, EMBASE, Web of Science, and Scopus. We screened titles, abstracts, and full texts for eligible articles focusing on patients undergoing therapy for cancer, employing ECAs, and reporting clinical outcomes.ResultsOf the 629 articles screened, 23 were included in this review. The earliest included studies were published in 1996, while most studies were published in the past 5 years. 44% (10/23) of ECAs were employed in blood-related cancer studies. Geographically, 30% (7/23) of studies were conducted in the United States, 22% (5/23) in Japan, and 9% (2/23) in South Korea. The primary data sources used to construct the ECAs involved pooled data from previous trials (35%, 8/23), administrative health databases (17%, 4/23) and electronic medical records (17%, 4/23). While 52% (12/23) of the studies employed methods to align treatment and ECAs characteristics, 48% (11/23) lacked explicit strategies.ConclusionECAs offer a valuable approach in oncology research, particularly when alternative designs are not feasible. However, careful methodological planning and detailed reporting are essential for meaningful and reliable results.
| S-EPMC11234289 | biostudies-literature
Project description: Not available
| S-EPMC9429252 | biostudies-literature