Panobinostat Recaptured Response in Bortezomib-Refractory Myeloma Patients

The addition of the oral pan-deacetylase inhibitor panobinostat to bortezomib helped to elicit responses in about one-third of heavily pre-treated patients with multiple myeloma who were refractory of bortezomib, according to the phase II results of the PANORAMA 2 study.

Researchers, led by Paul G. Richardson, MD, of Dana-Farber Cancer Institute, wrote that the results of this study point “to a role for panobinostat in combination with bortezomib and dexamethasone” in this patient population.

“This combination is also being studied in a large phase 3 trial (PANORAMA 1) in relapsed and relapsed and refractory patients with multiple myeloma,” the researchers wrote. “Taken together, these trials will better elucidate the role of panobinostat in combination with bortezomib and dexamethasone in advanced relapsed and refractory multiple myeloma.”

In this study, the researchers enrolled 55 patients with multiple myeloma aged 18 years or older between June 2010 and July 2011. All patients had been treated with at least two prior lines of therapy including an immunomodulatory drug, and had progressed on bortezomib. The median number of prior therapies was four.

The patients were treated initially with a 2 week on/1 week off schedule of panobinostat/bortezomib/dexamethasone. Seventeen patients who had evidence of clinical benefit continued treatment with a 6-week cycle of the drugs. The results of the study were published in Blood.

Overall, one patient achieved a near-complete response and 18 patients (32.7%) achieved a partial response, resulting in an overall response rate of 34.5%. The researchers found that an additional 10 patients (18.2%) achieved minimal response. The regimen resulted in a clinical benefit rate of 52.7%.

“In a review by Kumar et al, a similar patient population was found to have an overall response rate to bortezomib-containing therapy of only 20%,” the researchers wrote. “Thus, these results compare favorably with currently published data for a refractory multiple myeloma population.”

The median time to response in the 19 patients achieving partial response or better was 1.4 months, with a median duration of response of 6 months. For the entire patient population, the median progression-free survival was 5.4 months.

“Overall, the combination of panobinostat with bortezomib and dexamethasone was tolerable, with manageable toxicities,” the researchers wrote. “Thrombocytopenia was the most common hematologic grade 3/4 adverse event; however, it did not lead to discontinuation and proved manageable with platelet transfusion and dose reduction/interruption.”

The other common grade 3/4 adverse events included fatigue (20%) and diarrhea (20%). One patient experienced grade 3 peripheral neuropathy.