ABSTRACT
Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.
ABSTRACT
BACKGROUND: Systemic light chain (AL) amyloidosis is a rare and multisystem disease associated with increased morbidity and a poor prognosis. Delayed diagnoses are common due to the heterogeneity of the symptoms. However, real-world insights from Chinese patients with AL amyloidosis have not been investigated. OBJECTIVE: This study aimed to describe the journey to an AL amyloidosis diagnosis and to build an in-depth understanding of the diagnostic process from the perspective of both clinicians and patients to obtain a correct and timely diagnosis. METHODS: Publicly available disease-related content from social media platforms between January 2008 and April 2021 was searched. After performing data collection steps with a machine model, a series of disease-related posts were extracted. Natural language processing was used to identify the relevance of variables, followed by further manual evaluation and analysis. RESULTS: A total of 2204 valid posts related to AL amyloidosis were included in this study, of which 1968 were posted on haodf.com. Of these posts, 1284 were posted by men (median age 57, IQR 46-67 years); 1459 posts mentioned renal-related symptoms, followed by heart (n=833), liver (n=491), and stomach (n=368) symptoms. Furthermore, 1502 posts mentioned symptoms related to 2 or more organs. Symptoms for AL amyloidosis most frequently mentioned by suspected patients were nonspecific weakness (n=252), edema (n=196), hypertrophy (n=168), and swelling (n=140). Multiple physician visits were common, and nephrologists (n=265) and hematologists (n=214) were the most frequently visited specialists by suspected patients for initial consultation. Additionally, interhospital referrals were also commonly seen, centralizing in tertiary hospitals. CONCLUSIONS: Chinese patients with AL amyloidosis experienced referrals during their journey toward accurate diagnosis. Increasing awareness of the disease and early referral to a specialized center with expertise may reduce delayed diagnosis and improve patient management.
