Subcutaneous bortezomib was found to improve the tolerability of the panobinostat, bortezomib, and dexamethasone triplet therapy for patients with relapsed or refractory multiple myeloma, according to the results of the phase 2 PANORAMA-3 study.3
“Patients with relapsed or relapsed and refractory multiple myeloma who have progressed following multiple lines of therapy require treatment options that can overcome resistance to previous agents and produce durable responses,” the study authors wrote. “The long duration of response with panobinostat 20 mg three times
weekly in this study provides further evidence of the efficacy of the combination of a histone deacetylase inhibitor plus a proteasome inhibitor in this setting.”
The PANORAMA-3 study (ClinicalTrials.gov identifier: NCT02654990) enrolled 248 patients with myeloma who had received 1 to 4 prior lines of therapy, including an immunomodulatory agent. Patients were randomly assigned to receive oral panobinostat at 20 mg thrice weekly, 20 mg twice weekly, or 10 mg thrice weekly plus subcutaneous bortezomib and oral dexamethasone.
After a maximum of 8 treatment cycles, the overall response rate (ORR) was 62.2% (95% CI, 50.8-72.7) for the 20 mg thrice weekly group, 65.1% (95% CI, 53.8-75.2) for the 20 mg twice weekly group, and 50.6% (95% CI, 39.4-61.8) for the 10 mg thrice weekly group. Data from a post hoc analysis showed that the ORR was similar in patients aged 75 years or younger and those older than 75 years in the 20 mg thrice weekly group (62.5% vs 60.0%). In the other 2 dosing groups, the ORRs were higher in younger patients than older patients.
“The regimen with the highest dose and frequency of panobinostat administration (20 mg three times weekly) had the greatest efficacy but, as expected, was associated with a modestly increased rate of grade 3 or worse adverse events; however, the study was not
powered for statistical comparisons between groups,” the researchers wrote.
Grade 3 or 4 adverse events occurred in the majority of patients in all 3 groups: 91% of the 20 mg thrice weekly group, 83% of the 20 mg twice weekly group, and 75% of the 10 mg thrice weekly group. The most common grade 3 to 4 adverse events were thrombocytopenia and neutropenia.
Fourteen deaths occurred during the study period. Five deaths occurred in the 20 mg thrice weekly group; 3 in the 20 mg twice weekly group; and 6 in the 10 mg thrice weekly group. None were related to the study treatment.
“This finding suggests that the use of subcutaneous bortezomib, along with weekly bortezomib from the onset of treatment among older patients and for all patients beyond four cycles of treatment, meaningfully improves tolerability and patient outcomes,” the researchers concluded.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Laubach JP, Schjesvold F, Mariz M, et al. Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study. Lancet Oncol. 2021;22(1):142-154. doi:10.1016/S1470-2045(20)30680-X