Carfilzomib-panobinostat combo safe, effective for relapsed/refractory multiple myeloma
The combination of carfilzomib, a second generation proteasome inhibitor, and panobinostat, a histone deacetylase inhibitor, is a safe and effective steroid-sparing regimen for heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), a recent study has found.
Thirty-two RRMM patients (median age 66 years; 53 percent female) participated in the present study, most of whom (84 percent; n=27) were relapsed and refractory to their last line of treatment. The median number of previous lines of treatment was four.
The maximum tolerated doses (MTD) of carfilzomib and panobinostat were 36 mg/m2 and 20 mg, respectively. At these levels, the most common dose-limiting toxicities were grade 4 thrombocytopoenia and a grade 3 increase in creatinine levels.
Other treatment-related adverse events (AE) were also reported. Eleven (37 percent) patients developed at least one serious AE, while any-grade haematological AEs occurred in almost all (97 percent) of the participants. Treatment-emergent, nonhaematological AEs of any grade were similarly highly common (93 percent).
One patient developed a grade 3–4 cardiac AE, while another experienced cardiac arrest, a grade 5 AE. Six patients discontinued the study due to AEs such as thrombocytopoenia, bowel perforation and acute pancreatitis.
In terms of efficacy, the objective response rate (ORR) in the overall study sample was 57 percent. A third of the participants achieved partial response, while 17 percent and 7 percent showed very good partial response (VGPR) and complete response, respectively. The resulting clinical benefit rate was 70 percent. At the MTD, the ORR was 63 percent, and 25 percent of the participants achieved VGPR or better.