Study Reveals Outcomes of Panobinostat in Heavily Pretreated Multiple Myeloma Patients

Introduction

Multiple myeloma, a largely incurable disease, has seen improved patient outcomes due to major advances in therapy. Panobinostat (PANO), an oral pan histone-deacetylase (HDAC) inhibitor, was approved for treating relapsed or refractory multiple myeloma but was withdrawn from the US market in March 2022 due to the lack of feasibility in completing required postmarketing trials. However, it remains a viable treatment option in Europe for patients whose disease has progressed after receiving other standard therapies.

Study Overview

A retrospective analysis was conducted on 105 patients with multiple myeloma treated with panobinostat at The Mount Sinai Hospital in New York City between October 2012 and October 2021. These patients, with a median age of 65, had received a median of 6 prior lines of therapy. Over half of the patients (53%) had triple class refractory disease, and 54% had high-risk cytogenetics.

Treatment and Outcomes

Panobinostat was most commonly used at 20 mg, primarily in triplet (61.0%) or quadruplet (30.5%) combinations. The most common combinations included lenalidomide, pomalidomide, carfilzomib, and daratumumab. Among the 101 response-evaluable patients, the overall response rate was 24.8%, with a clinical benefit rate (≥minimal response) of 36.6%. The median progression-free survival was 3.4 months, and the median overall survival was 19.1 months. The most common toxicities ≥grade 3 were hematologic, including neutropenia (34.3%), thrombocytopenia (27.6%), and anemia (19.1%).

Discussion

Despite the challenges in treating heavily pretreated multiple myeloma, panobinostat-based combinations were found to be well-tolerated and produced modest response rates. This is particularly significant for triple-class refractory patients, who have very limited treatment options. The study underscores the need for continued investigation into panobinostat as a tolerable oral option for recapturing responses in patients whose disease has progressed after standard-of-care therapies.

Conclusion

Panobinostat-based combination therapies offer a promising avenue for the treatment of heavily pretreated multiple myeloma patients, especially those with triple-class refractory disease. The future utility of HDAC inhibitors may be further enhanced by developments in precision medicine techniques and advances in genomic and epigenomic profiling.