Bringing the Oncology Community Together

Studies Highlight Newly Approved and Novel Multiple Myeloma Treatments

Barbara L. Jones
Published Online: Friday, July 26, 2013
Katja C. Weisel, MD

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 =.028).

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 <.001).

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

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.

Page: 12Next Page (2) >>
Related Articles
MSK's CAR Trials Halted Temporarily Amid Safety Review
Five early-phase clinical trials exploring chimeric antigen receptor (CAR) T-cell therapy have been suspended temporarily in response to the deaths of 2 patients with adult B-cell acute lymphoblastic leukemia
Defining and Predicting Response to HMAs in MDS
In this segment, panelists discuss the lack of a clear connection between response to hypomethylating agents and molecular genetics as well as the larger role for cytogenetic assessment of response for patients with myelodysplastic syndrome.
Limited Availability of Non-Caucasian Stem Cell Donors: A Growing Problem?
To address the challenge of the limited availability of stem cell donors in non-Caucasians, it is vital that we increase awareness through more campaigns that are targeted specifically to minorities.
David Lucas Discusses the Bromodomain Inhibitor OTX015
David Lucas, PhD, assistant professor, division of hematology, Ohio State University, discusses the bromodomain inhibitor OTX015.
Most Popular Right Now
More Reading
External Resources

American Journal of Managed Care
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Specialty Pharmacy Times
OncLive Resources

OncLive TV
Oncology Nurses
Web Exclusives

About Us
Advisory Board
Contact Us
Forgot Password
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright OncLive 2006-2014
Intellisphere, LLC. All Rights Reserved.