Charles Dharmani

Background: Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive type of peripheral T-cell malignancy caused by the human T-lymphotropic virus type 1 (HTLV-1). Approximately 5 to 10 million people are infected with HTLV-1 worldwide, with high prevalence in Japan. This observational study analyzed patient characteristics, treatment patterns, healthcare resource utilization (HRU), and costs of ATL in Japan. Methods: A retrospective analysis of ATL patients from the Medical Data Vision database, Sept. 1, 2012–Aug. 31, 2022, was conducted. Results: Among 1572 ATL patients, 384 received systemic therapy. The mean age at diagnosis was 66.4 years, with 63.7% being ≥65 years; 55.2% patients were females. Excluding cancer, 61% of patients had a Charlson Comorbidity Index score of 0. The most frequently observed comorbidities were congestive heart failure (15.8%), diabetes (14.8%), and peptic ulcer disease (14.6%). Among the treated patients, 37.5% received 1 line of therapy, 26% received 2 lines of therapy, and 36.5% received ≥3 lines. Mogamulizumab was most frequently utilized (60.4%), as monotherapy or in combination regimens. The most common combination regimen in all lines of therapy were cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), utilized in 46.6% of patients. Additionally, use of combinations such as VCAP-AMP-VECP, which include vincristine, cyclophosphamide, doxorubicin, and prednisone; adriamycin, manimustine, and prednisone; and vindesine, etoposide, carboplatin, and prednisone, was observed in 33.3% of patients. Initial treatment was discontinued in 74.7% patients; only 3.4% received stem cell transplants. Most (96%) patients were hospitalized, 29.7% had emergency room visits, and 79.4% averaged 1.8 outpatient visits monthly. The mean all-cause healthcare cost per patient per month was $29 538 (¥4 647 300), mainly due to outpatient visits and hospitalizations. Conclusion: Although real-world studies based on MDV database have certain limitations, the findings of this study provide deeper understanding of the real-world patient characteristics, treatment patterns, HRU, and costs of ATL patients in Japan. The results indicate that patients often encounter high treatment costs and frequent hospitalizations, demonstrating the necessity for advanced regimens and highlighting the unmet need for more effective therapies in ATL patients that may reduce HRU and economic burden in this patient population.

Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non-Hodgkin lymphomas associated with aggressive clinical course and suboptimal outcomes. PTCL accounts for a higher proportion of non-Hodgkin lymphoma cases in Japan compared with Western countries; however, real-world evidence on treatment patterns, healthcare resource utilization (HRU), and costs in Japan is limited. Objectives: To describe real-world patient characteristics, treatment patterns, HRU, and costs among patients with PTCL in Japan. Methods: This retrospective observational study used administrative claims data from the Medical Data Vision database in Japan. Adult patients diagnosed with PTCL between September 2012 and August 2022 were identified. Patients were categorized as receiving nonsystemic therapy or systemic therapy and stratified by lines of therapy. Patient demographics, comorbidities, treatment regimens, time on treatment, HRU, and healthcare costs, measured per patient per month, were analyzed descriptively. Results: Among 910 patients identified, 71.3% received systemic treatment and 28.7% received nonsystemic therapy, most receiving corticosteroids only. Mean age at diagnosis was 69.8 years; 70% of patients were at least 65 years old. Key comorbidities included peptic ulcer disease, congestive heart failure, and diabetes. PTCL–not otherwise specified and angioimmunoblastic T-cell lymphoma accounted for over 75% of subtypes. First-line therapy was mainly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens; later lines were more heterogeneous and of shorter duration. Mogamulizumab and brentuximab vedotin were used in 4.16% and 10.48% of patients, respectively. Stem cell transplantation was infrequent (6.3%). Median per patient per month PTCL-related total healthcare cost was $9712; median drug ($7056.9) and hospitalization costs ($5177.7) were the main contributors. Discussion: These findings demonstrate substantial clinical and economic burden among PTCL patients in Japan. Treatment heterogeneity and short duration in later lines of therapy highlight ongoing therapeutic challenges. Conclusions: High economic burden of PTCL treatment underscores the need for more effective, tolerable, and less costly therapeutic strategies for treating PTCL patients in Japan.

To assess hepatic safety data of pexidartinib in adult patients with tenosynovial giant cell tumor (TGCT) from the retrospective 5-year evaluation of the TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) Program. We analyzed data collected from healthcare professionals, patients, pharmacies, and distributors who participated in the tREMS Program from August 2019 to June 2024. For the current reporting period, June 2022 to June 2024, of the 524 patients enrolled in the tREMS with ≥ 1 dispense of pexidartinib, 24 (4.6%) had adverse events or laboratory abnormalities suggestive of serious and potentially fatal liver injury, with a total of 45/735 (6.1%) patients over 5 years. One (0.2%) patient in the current period had confirmed vanishing bile duct syndrome (VBDS) and was recovering at last follow-up. Another patient from the previous reporting period had unconfirmed VBDS and was alive with unknown recovery status at last follow-up. For the current reporting period and cumulative 5-year tREMS assessment, the reported frequency and pattern of liver injury were consistent with the phase 3 ENLIVEN trial. The tREMS Program effectively mitigates the risk of hepatotoxicity through careful monitoring and early intervention. Pexidartinib remains a viable treatment option for TGCT when managed according to recommended guidelines.

Validating an operational algorithm for identifying ventricular arrhythmia and sudden cardiac arrest (VA/SCA) in electronic health record (EHR) data may be useful to minimize measurement bias in studies characterizing real-world VA/SCA risk; however, validation studies require an appropriate reference standard. We aimed to assess if adequate information is documented in unstructured clinical notes of a large EHR database to serve as a reference standard for future validation studies of VA/SCA. Twenty potential VA/SCA events were randomly selected from unstructured clinical notes of a large EHR database, TriNetX Dataworks - USA. These notes were reviewed to assess if key clinical elements were documented to confirm the occurrence of VA/SCA and describe their clinical features. These included explicit documentation of an acute event, electrocardiogram (ECG) findings, urgent medical interventions, and other elements. Explicit documentation of an acute event was recorded for 17 patients (85.0%) and ECG findings were documented for 15 patients (75.0%). Generally, unstructured clinical notes also contained information about signs and symptoms, care setting, medical interventions administered, and event resolution. The unstructured clinical notes of a large EHR database contained the information necessary to serve as a reference standard for validation studies of a VA/SCA operational algorithm in EHR data.

Aim: Hepatic safety data assessment from the TURALIO^® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program.Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program.Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified.Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity.

Breast cancer treatments have evolved rapidly, and clinically meaningful biomarkers have been used to guide therapy. These biomarkers hold utility within the drug development process to increase th...

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or f... Plain language summary – Treatment patterns in patients with tenosynovial giant cell tumors in the USA This database study is the first investigation of how drugs are used to treat patients with te...

Objective: To evaluate treatment patterns, healthcare resource utilization (HRU) and costs among peripheral T-cell lymphoma (PTCL) patients in the USA. Methods: A retrospective cohort study, using ... Plain language summary – How are patients with peripheral T-cell lymphoma treated in the real world & how much does it cost? Peripheral T-cell lymphomas (PTCL) are a rare and fast-growing form of b... Tweetable abstract Treatment patterns and costs in peripheral T-cell lymphoma.