MM-003: Panobinostat: A Light at the End of the Tunnel

Abstract

Panobinostat, a pan histone deacetylace inhibitor, was approved by FDA in 2015 for treatment of relapsed myeloma that progressed after at least 2 lines of therapy including IMiDs. Its toxicity, mainly severe diarrhoea and cardiac events, became its limiting factor for widespread use. Its availability in India since 2018 broadened our choice to treat patients in a cost-effective manner who had otherwise exhausted all their options. Our data includes limited number of 8 patients aged 38-77yrs in single centre from 2018-2019 and was very encouraging. Panobinostat, bortezomib, and dexamethasone combination was used mainly as 5th or 6th line of treatment. Dose of panobinostat was escalated starting with 10 mg thrice weekly on 2-week on 1-week off cycle. Maximum tolerated dose was 15 mg. Bortezomib 1.3 mg/m2 given on a weekly schedule along with dexamethasone 20-40 mg based on age and comorbidities. Median number of cycles given were 6 (1-10). Results: ORR was 85% patients with reduction in their paraprotein or light chains after 1st cycle. 1 patient achieved a CR with disappearance of M band, 1 patient died shortly due to progressive disease and the remaining achieved VGPR. The duration of response varied from 6 months to a year. The main side effects were severe fatigue, grade 2 thrombocytopenia, and mild diarrhoea not requiring hospitalisation. It was impressive that even patients who failed monoclonal antibodies daratumumab and elotuzumab had an objective response. Its activity is demonstrated even in the high-risk cytogenetic group including 17p deletion. Conclusion: Our retrospective analysis confirms the efficacy of panobinostat in a relapsed refractory setting with manageable toxicities through all age groups. The dose of panobinostat was the key factor in limiting the toxicity. Considering the health-related economics in a resource constrained setting an outpatient-based treatment is a very attractive option. The cost of therapy with monoclonal antibodies is prohibitive to most of our population. With reduced hospital inpatient days and visits, the reported quality of life was much better. We aim to gather more data from other centres in our state.