Relapsed and Bortezomib-Refractory Multiple Myeloma (MM) Patients Show Response to Treatment with Panobinostat + Bortezomib + Dexamethasone

Share this content:

SAN DIEGO, CA—Use of the pan-deacetylase inhibitor panobinostat in combination with bortezomib and dexamethasone is promising for patients with bortezomib-refractory MM, results PANORAMA 2, a single arm, Phase 2 study presented at the 53rd American Society of Hematology Annual Meeting and Exposition have found.

Panobinostat is an oral pan-deacetylase inhibitor that intensifies acetylation of proteins involved in various oncogenic pathways. Clinical responses (≥minimal response [MR]) have been seen in 65% of patients with relapsed or relapsed/refractory MM treated with panobinostat + bortezomib (including patients with bortezomib-refractory disease) in a Phase 1 study.

Patients in this study were either relapsed or were bortezomib-refractory, defined as having received ≥2 prior lines of therapy including an immunomodulary drug (thalidomide or lenalidomide) and progression on or within 60 days of the last bortezomib-based therapy. Patients were treated in two phases. The first treatment phase included eight three-week cycles of oral panobinostat 20mg on Days 1, 3, 5, 8, 10, 12; intravenous bortezomib 1.3mg/m2 on Days 1, 4, 8, 11; and oral dexamethasone 20mg on the day of and after bortezomib. The second treatment phase was reserved for patients displaying clinical benefit (≥stable disease) and included six-week cycles of panobinostat 20mg three times weekly, two weeks on and one week off (repeating), bortezomib 1.3mg/m2 on Days 1, 8, 22, and 29, and dexamethasone 20mg on the day of and after bortezomib, given until disease progression.

The study's primary endpoint is overall response (OR=complete response [CR] + near CR [nCR] + partial response [PR]), as defined by the European Group of Blood and Marrow Transplantation 1998 criteria, in the first eight cycles of Phase 1 treatment. Four or more PR in 24 patients were needed in stage 1 in order for the study to advance to stage 2.

A total of 55 patients were enrolled in the trial. Patients received a median of four (range 2–14) prior regimens; most patients (69%) had prior autologous stem cell transplant.

At the time of assessment, OR was observed in 16 patients (29%; 0 CR, 2 nCR, 14 PR). Clinical benefit (OR + minimal response [MR]) was documented in 27 patients (49%), and very good PR (VGPR) in three patients (6%). Stable disease was observed in two patients and progressive disease in 10 patients. Mean duration of the study is 4.7 months (range <1–12.5). Sixteen patients have completed the first eight cycles and have entered the second phase of the study: 10 patients remain in phase 2 and two patients have completed ≥12 cycles.

Any grade common adverse events included fatigue (63%), treatment-emergent neuropathy (24%), and asthenia (14%) and were predominantly mild. The most common Grade 3/4 adverse event was thrombocytopenia (53%); this was managed with dose reductions/interruptions and were observed less when panobinostat was dosed two weeks on and one week off compared with the weekly schedule.

The data from this trial, along with that of a Phase 3 study of panobinostat/placebo + bortezomib + dexamethasone in patients with relapsed MM, will additionally characterize the budding use of panobinostat in the treatment of patients with MM, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, MA, stated.

You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs