MM-102: Outcomes of Panobinostat with Proteasome Inhibitor or Immunomodulator-Based Therapies in Patients with Relapsed/Refractory Multiple Myeloma: A Single-Center Experience

Background: Panobinostat (pano) is a pan histone deacetylase inhibitor (HDAC-i) FDA-approved 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). This retrospective study evaluates efficacy and safety of pano combined with other FDA-approved agents used in relapsed/refractory (RR) MM. Methods: From February 2015-July 2017, 47 consecutive patients with RRMM treated with commercial pano identified in the EMR were reviewed. Results: Median age was 58.7 (27-78) years with 55% men. 41 (87%) were Durie-Salmon Stage 3. 12 (26%) had high-risk FISH: t(14;16), t(4;14), del 17p, and gain 1q21. Median number of prior lines was 6 (2-14). 38 (81%) were RR to the last line of therapy. 29 (62%) were btz-refractory, 36 (77%) lenalidomide-refractory, 36 (77%) pomalidomide-refractory, and 36 (77%) carfilzomib-refractory. 33 (70%) were refractory to carfilzomib with an IMiD. 15 (32%) had prior daratumumab and 7 (15%) had prior HDAC-i therapy. Median pano cycles was 3 (0.25-18). ORR (≥PR) was 25.0% and clinical benefit rate (≥MR) was 38.6%. Median duration of response (≥SD) was 4.3 months. Median PFS was 2.4 months (95% CI: [1.61,4.01]). Median OS from initiation of pano through 1/16/19 was 6.25 months (95% CI: [5.10,12.95]). Three patients discontinued pano due to toxicity. Grade 3-4 non-hematologic toxicities were diarrhea (N=1), and respiratory failure (N=2). Grade 3-4 hematologic adverse events (AEs) occurred in 19 (40%) patients, 12 (26%) with anemia,15 (32%) with neutropenia, and 13 (28%) with thrombocytopenia. Serious AEs included acute kidney injury, GI bleed, febrile neutropenia, heart failure exacerbation, and dyspnea in 4 patients, respectively. PFS is negatively associated with a greater number of lines of treatment prior to initiating pano (HR 1.21: 95% CI 1.02-1.4). High-risk FISH (HR 0.71: 95% CI 0.31-1.60) and being refractory to the last prior line of therapy (HR 0.51: 95% CI 0.17-1.60) show no significant association with PFS. Conclusion: Use of pano outside of the FDA indication, in combination with PI and IMiD-based regimens, has activity and is well tolerated in heavily pretreated RRMM patients.