Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment

Area of Science:

• Oncology
• Pharmacology
• Epigenetics

Background:

• Panobinostat is a pan-deacetylase inhibitor impacting multiple myeloma (MM) cell growth via epigenetic and metabolic alterations.
• The combination of panobinostat, bortezomib, and dexamethasone (PAN-BTZ-Dex) showed improved progression-free survival (PFS) in MM patients.
• Subgroup analyses are crucial for understanding treatment efficacy in diverse patient populations with relapsed or refractory MM.

Purpose of the Study:

• To evaluate the efficacy of PAN-BTZ-Dex versus placebo plus bortezomib and dexamethasone (Pbo-BTZ-Dex) in relapsed/refractory MM patients based on prior treatment history.
• To assess PFS and safety outcomes in specific subgroups: prior immunomodulatory drug (IMiD), prior bortezomib plus IMiD, and multiple prior regimens including bortezomib and IMiD.

Main Methods:

• Analysis of data from the phase 3 PANORAMA 1 trial.
• Patients were stratified into subgroups based on prior treatment regimens.
• Comparison of median PFS, hazard ratios (HR), and confidence intervals (CI) between PAN-BTZ-Dex and Pbo-BTZ-Dex arms.

Main Results:

• PAN-BTZ-Dex consistently improved median PFS across all analyzed subgroups compared to Pbo-BTZ-Dex.
• Significant PFS benefits observed: prior IMiD (12.3 vs 7.4 months), prior bortezomib plus IMiD (10.6 vs 5.8 months), and ≥2 prior regimens (12.5 vs 4.7 months).
• Common grade 3/4 adverse events included thrombocytopenia, lymphopenia, neutropenia, diarrhea, and fatigue; on-treatment deaths were similar between arms in bortezomib/IMiD-treated patients.

Conclusions:

• PAN-BTZ-Dex offers a significant PFS benefit in relapsed/refractory MM patients, irrespective of prior treatment exposure.
• The combination therapy provides a notable 7.8-month PFS advantage in patients with ≥2 prior regimens including bortezomib and IMiD, a group with limited options.
• The safety profile was consistent with known side effects, and the benefit-risk profile supports its use in this patient population.