인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Simultaneously targeting key pathogenic drivers and remodeling of the tumor microenvironment represents a critical therapeutic strategy for relapsed or refractory (r/r) multiple myeloma (MM) and lymphoma. Purinostat mesylate (PM), a highly selective HDAC I/II binhibitor, exhibits excellent antitumor activity in MM and lymphoma cell lines and mouse models, outperforming the pan-HDAC inhibitor panobinostat or first-line/second-line multi-drug combinations. Different from panobinostat, bulk RNA-seq analysis revealed that PM suppressed essential tumor survival factors and triggered inflammation and interferon responses. The scRNA-seq of 5TMM models further indicated that PM enhanced antitumor immunity by boosting monocyte- and T cell-mediated immune responses. In a phase I trial (NCT05526313; N = 29) of PM at doses up to 15 mg/m², treatment-related Grade ≥3 adverse events predominantly comprised hematologic toxicities: thrombocytopenia (75.9%), neutropenia (55.2%), leukopenia (41.4%), and lymphopenia (31.0%), with no dose-limiting toxicities observed. PM monotherapy achieved a disease control rate of 72.7% (8/11) and an objective response rate (ORR) of 9.1% (1/11) in r/r MM. Notably, r/r lymphoma patients showed an ORR of 61.6% (11/18), particularly reaching 63.6% (7/11) with 6 complete responses in diffuse large B-cell lymphoma (DLBCL). Treatment responders exhibited enhanced immune activation, with elevated CD3<sup>+</sup>CD8<sup>+</sup> T cells and increased cytokine levels, such as IFN-γ and CXCL10. Overall, PM is safe and moderately effective in MM, but highly effective in lymphoma. Additionally, PM combined with pomalidomide and dexamethasone showed strong synergistic activity in r/r MM treatment. These findings support further open-label, multicenter phase Ib/IIa trials of PM combination therapy with immunomodulators for r/r MM, as well as phase II monotherapy trials for r/r DLBCL and r/r T-cell lymphoma.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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