DREAMM-11, Part 2: Japanese phase I trial of belantamab mafodotin combination therapies in relapsed/refractory multiple myeloma.

DREAMM-11 (NCT03828292) was a Phase 1, open-label, dose-escalation study of belantamab mafodotin in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In Part 1, belantamab mafodotin monotherapy (2.5 or 3.

A prospective study comparing highly qualified Molecular Tumor Boards with AI-powered software as a medical device.

Background: The implementation of cancer precision medicine in Japan is deeply intertwined with insurance reimbursement policies and requires case-by-case reviews by Molecular Tumor Boards (MTBs), which impose considerable operational burdens on healthcare facilities. The extensive preparation and review times required by MTBs hinder their ability to efficiently assess comprehensive genomic profiling (CGP) test results. Despite attempts to optimize MTB operations, significant challenges remain.

Drug-resistant F V600E-mutant recurrent pleomorphic xanthoastrocytoma, CNS WHO Grade 3 successfully resolved with incidental discontinuation of combined BRAF and MEK inhibitor therapy.

Background: Combination therapy with BRAF and MEK inhibitor holds promise for treating gliomas harboring the V600E mutation; however, the development of acquired resistance remains a challenge.

Case Description: We describe a case of repeated recurrent mutant pleomorphic xanthoastrocytoma (central nervous system World Health Organization grade 3) treated with combination therapy with BRAF and MEK inhibitor. The patient received dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor); however, she developed resistance to the combination therapy.

A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2.

Efficacy of Trametinib in Neurofibromatosis Type 1-Associated Gastrointestinal Stromal Tumors: A Case Report.

Trametinib, an MEK inhibitor, may offer a new therapeutic option for patients with NF1-related GIST.

Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population.

Background: Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment.

Remission induced by renal protective therapy in nephrotic syndrome with thin basement membrane in an older patient: a case report.

Background: Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment varies according to its underlying cause but often faces medication resistance or adverse drug effects.

Case Presentation: A Japanese woman in her 80s presented with nephrotic syndrome after a 3 year latent period of urinary protein and occult blood.

The impact of rare cancer and early-line treatments on the benefit of comprehensive genome profiling-based precision oncology.

Background: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP.

Materials And Methods: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer.

Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021).

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018.

Identification of barriers to implementation of precision oncology in patients with rare cancers.

Established treatment options for rare cancers are limited by the small number of patients. The current comprehensive genomic profiling (CGP) testing might not fully exploit opportunities for precision oncology in patients with rare cancers. Therefore, we aimed to explore the factors associated with CGP testing utility in rare cancers and identify barriers to implementing precision oncology.

Passive Smoking-Induced Mutagenesis as a Promoter of Lung Carcinogenesis.

Introduction: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a group 1 carcinogen linked to lung cancer. However, in contrast to active smoking, the mutagenic properties of PS remain unclear.

Methods: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared.

Dabrafenib and trametinib administration in patients with V600E/R or non-V600 mutated advanced solid tumours (BELIEVE, NCCH1901): a multicentre, open-label, and single-arm phase II trial.

Background: V600 mutations are common in melanoma, thyroid, and non-small-cell lung cancers. Despite dabrafenib and trametinib being standard treatments for certain cancers, their efficacy across various solid tumours remains unelucidated. The BELIEVE trial assessed the efficacy of dabrafenib and trametinib in solid tumours with V600E/R or non-V600 mutations.

Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Promotes Oral Cancer Progression by Activating YAP.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms.

Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial.

Background: Precision medicine has transformed cancer treatment by focusing on personalized approaches based on genomic abnormalities. However, comprehensive genomic profiling (CGP) and access to targeted therapies are limited in Japan. This study investigates the BELIEVE trial, which aims to improve drug accessibility for patients with actionable genetic abnormalities through off-label drug administration.

Progress report of a cross-organ and biomarker-based basket-type clinical trial: BELIEVE Trial.

Cancer genomic medicine using next-generation sequencers has been developing. However, the number of patients who could receive genomically matched therapy is limited because off-label use or patient-oriented compassionate use was not permitted under National Health Insurance in Japan. To improve patient drug accessibility, we initiated a biomarker-based basket-type clinical trial (NCCH1901) in October 2019 under patient-proposed healthcare services.

High-grade intraductal carcinoma of the parotid gland harboring CTNNA1::ALK rearrangement: Changes in genetic status using genetic testing during treatment with an ALK inhibitor.

Background: Salivary gland carcinomas harboring anaplastic lymphoma kinase (ALK) rearrangements are rare. Here, we present the pathological characteristics, clinical course, and changes in the genetic status of a salivary gland carcinoma harboring a catenin alpha 1 (CTNNA1)::ALK rearrangement during treatment with an ALK tyrosine kinase inhibitor (TKI).

Methods: A 59-year-old man with a parotid tumor and cervical lymph node metastases underwent total parotidectomy and radical neck dissection.

Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci.

Background: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice.