4.4 Review

Outcomes with panobinostat in heavily pretreated multiple myeloma patients

Journal

SEMINARS IN ONCOLOGY
Volume 50, Issue 1-2, Pages 40-48

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.seminoncol.2023.03.006

Keywords

Panobinostat; Histone deacetylase inhibitor; Relapsed refractory multiple myeloma; HDAC inhibitor; Multiple myeloma

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This study retrospectively analyzed the efficacy and safety of Panobinostat-based combinations in heavily pretreated multiple myeloma patients. The results showed that Panobinostat, when combined with other drugs, achieved modest response rates but had significant toxicities in this patient population.
Panobinostat is an oral pan histone-deacetylase inhibitor used in the treatment of relapsed and refractory multiple myeloma. Previously published studies of panobinostat demonstrated synergy with bortezomib but included few patients exposed to newer agent combinations (ie, panobinostat plus daratumumab or carfilzomib). Here, we report outcomes of panobinostat-based combinations at an academic medical center among patients whose disease had been heavily pretreated with modern agents. We retrospec-tively analyzed 105 patients with myeloma treated with panobinostat at The Mount Sinai Hospital in New York City between October 2012 and October 2021. These patients had a median age of 65 (range 37-87) and had received a median of 6 prior lines of therapy while in 53% the disease was classified as triple class refractory and in 54% the disease had high-risk cytogenetics. Panobinostat was most com-monly utilized at 20 mg (64.8%) as part of a triplet (61.0%) or quadruplet (30.5%). Aside from steroids, panobinostat was most commonly administered in combination with lenalidomide, pomalidomide, carfil-zomib, and daratumumab in descending order of frequency. Among the 101 response-evaluable patients, the overall response rate was 24.8%, clinical benefit rate ( & GE;minimal response) was 36.6%, and median progression-free survival was 3.4 months. Median overall survival was 19.1 months. The most common toxicities & GE;grade 3 were hematologic, primarily neutropenia (34.3%), thrombocytopenia (27.6%), and ane-mia (19.1%). Panobinostat-based combinations produced modest response rates in patients with heavily pretreated multiple myeloma, over half of whom had triple-class refractory disease. Panobinostat war-rants continued investigation as a tolerable oral option for recapturing responses in patients whose dis-ease has progressed after receipt of standard-of-care therapies.& COPY; 2023 Elsevier Inc. All rights reserved.

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