English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

This phase I/II trial was conducted to investigate the safety, efficacy, and pharmacodynamics of the pan-HDAC-inhibitor (HDACi) vorinostat combined with bortezomib, doxorubicin, and dexamethasone (VBDD) in patients suffering from relapsed/refractory multiple myeloma (RRMM). In the phase I part of this study, 9/33 patients received dose-escalated vorinostat (100, 200, 300mg), using a 4-day-on and 4-day-off schedule, and a standard 3+3 design. In the phase II part of the study, 24/33 patients were included to further assess VBDD's safety and efficacy. Complementary analyses were performed throughout the trial to correlate clinical outcome with patient fitness, pharmacodynamics and potential biomarkers. The number of prior therapy lines was substantial with a median of 3 (1-9; prior bortezomib treatment: 88%). VBDD was well tolerated with no dose-limiting toxicity: 15 adverse events occurred in 9/33 (27%) patients. The best overall response rate was 67% and clinical benefit rate 94%. With a median follow-up of 30.8 months, median progression-free- and overall-survival were 9.6 and 33.8 months, respectively. VBDD-responders showed early pan-HDAC activity decreases in peripheral blood mononuclear cell samples (median 45% of pre-treatment levels), of bone marrow (BM) infiltration rates and of BM-HDAC6 expression. VBDD proved to be an effective, well-tolerated outpatient quadruplet regimen with promising responses in RRMM. Our intermittent HDACi schedule provides a novel treatment option as compared to previous maximum-tolerated-dose-driven HDACi approaches and may serve as a useful example for other HDACi combinations, demonstrating that a continuous epigenetic treatment, with proven synergy to antimyeloma agents, is relevant before HDACi are dismissed as antimyeloma agents.

haematologica

Safety and efficacy of vorinostat, bortezomib, doxorubicin and dexamethasone in a phase I/II study for relapsed or refractory multiple myeloma (VERUMM study: vorinostat in elderly, relapsed and unfit multiple myeloma)