Katja C. Weisel, MD
Researchers highlighted the latest developments in the treatment of multiple myeloma at the 2013 ASCO Annual Meeting. Noteworthy abstracts included updated data on pomalidomide (Pomalyst), which the FDA recently approved, as well as research involving the promising novel agents daratumumab and elotuzumab.
New Standard of Care in Relapsed/Refractory MM
Pomalidomide plus low-dose dexamethasone “should become the standard of care for patients with relapsed/refractory multiple myeloma (MM) after treatment with lenalidomide and bortezomib,” said Katja C. Weisel, MD, associate professor at University Hospital Tuebingen in Germany, reflecting the views of an international group of investigators taking part in the large MM-003 trial.1
The phase III MM-003 study enrolled 455 patients with relapsed or refractory MM. Eligible patients were refractory to their last prior therapy, had progressive disease during therapy or within 60 days, and had failed lenalidomide and bortezomib after two or more cycles of each therapy alone or in combination.
Patients were randomized 2:1 to a combination of pomalidomide plus low-dose dexamethasone (n = 302) or to high-dose dexamethasone (n = 153). At a median follow-up of 4 months, when the primary analysis was performed, patients receiving the combination of pomalidomide plus low-dose dexamethasone had significantly longer median progression-free survival (PFS), at 3.6 versus 1.8 months (hazard ratio [HR] = 0.45; P
<.001) and overall survival (OS; not reached vs 7.8 months; HR = 0.53; P
<.001) compared with patients receiving high-dose dexamethasone. The observed OS benefit included 29% of patients who received pomalidomide after experiencing progressive disease on high-dose dexamethasone. Weisel reported data from an updated analysis after a median follow-up of 10 months. At this time, PFS and OS continued to favor treatment with pomalidomide plus low-dose dexamethasone, with median PFS of 4 versus 1.9 months (HR = 0.48; P
<.001) and median OS of 12.7 versus 8.1 months (HR = 0.74; P
The investigator-assessed overall response rate for patients in the pomalidomide arm was 31% versus 10% in the high-dose dexamethasone arm (P
<.001), and 24% versus 3% for patients who were randomized 6 months or more after enrollment (P
The most frequent grade 3/4 adverse event for the pomalidomide combination was neutropenia (48%). Commenting on this rate of neutropenia, Weisel noted that there were only a few febrile complications.
On February 8, 2013, the FDA approved oral pomalidomide for the treatment of patients with MM who have received at least two prior therapies, including lenalidomide and bortezomib, and who have had disease progression on or within 60 days of completion of the last therapy.
CD38 Monoclonal Antibody Yields “Unprecedented” Early-Stage Data
The investigational monoclonal antibody (mAb) daratumumab targets the CD38 molecule, which is highly expressed on the surface of multiple myeloma (MM) cells. Daratumumab has been shown to have broad-spectrum cytotoxic activity; it acts by mediating killing of CD38-expressing tumor cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis.
In a phase I/II dose-escalation study reported by Henk Lokhorst, MD, PhD, from UMC Utrecht, The Netherlands, for an international group of researchers at ASCO 2013, the performance of daratumumab in patients with relapsed/refractory MM was described as “unprecedented for a single-agent mAb treatment of multiple myeloma.”2
Sagar Lonial, MD
In early May, the FDA granted Breakthrough Therapy Designation for daratumumab for the treatment of patients with MM who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or for patients who are double-refractory to both classes of drugs.
Following on previously published safety and efficacy data, an international group of researchers reported finalized part 1 and preliminary safety data from an ongoing part 2 of the study, which enrolled patients aged 18 years and older with MM that was relapsed or refractory to at least two prior lines of therapy. Patients must also have been ineligible for transplant.