Real-world outcomes with panobinostat in patients with penta- and quad-refractory multiple myeloma.

Abstract

e19522 Background: Panobinostat (pano) is a pan histone de-acetylatase inhibitor (HDAC-i) approved by the FDA for use with bortezomib (btz) and dexamethasone (dex) for patients with multiple myeloma (MM) who have had ≥2 prior lines of therapy including both btz and an immunomodulatory agent (IMiD). The goal of this retrospective study is to evaluate the efficacy and safety of pano in combination with a variety of FDA approved agents as would be utilized in a real world management in relapsed/refractory (RR) MM. Methods: Between February 2015 and July 2016, 37 consecutive patients with RRMM treated with commercial pano were identified and the electronic medical record was reviewed. Results: Median age was 62 (range 27-78), with 57% percent male. Ten (27%) had high-risk FISH as defined by t(14;16), t(4;14), del p53, and gain 1q21. Median number of prior lines was 6 (range 2-9). All patients were RR to their last line of therapy, and 20 (54%) were btz-refractory, 27 (73%) were lenalidomide-refractory, 29 (78%) were pomalidomide-refractory, and 29 (78%) were carfilzomib-refractory. Thirty-three (89%) were penta-refractory; eight (21%) were penta-refractory, and 4 (11%) were refractory to prior HDAC-i therapy. Median number of cycles with pano was 2 (range 0.25 - 10). The overall response rate (≥ partial response) was 29.4% and the clinical benefit rate (≥ minor response) was 71.4%. Median progression-free survival was 2.4 months (95% CI: [1.63 – 4.43]). Median duration of response (≥SD) was 4.1 months. Median overall survival from initiation of pano was 7.5 months (95% CI: [5.17, NA]). One patient discontinued pano due to AEs. Grade 3 and 4 non-hematologic toxicities were diarrhea (N = 1), and respiratory failure (N = 1). Grade 3 and 4 hematologic adverse events (AEs) occurred in 13 (35%) patients, with 7 (19%) anemia, 11 neutropenia (30%), and 10 (37%) thrombocytopenia. Serious AEs included acute kidney injury, GI bleed, and febrile neutropenia each occurring in 1 patient. Conclusions: Use of pano outside of the FDA indication in combination with PI and IMiD-based regimens has activity and is well tolerated in quad and penta-refractory MM patients.