New Paradigm Emerging in Multiple Myeloma Therapy

Sara Thier, PhD, MPH
Published: Thursday, May 14, 2015
Dr. A. Keith Stewart

A. Keith Stewart, MB ChB

The emerging treatment landscape for patients with high-risk multiple myeloma is burgeoning with new classes of drugs, novel agents, and fresh combination strategies that offer many promising and exciting options for future therapeutic approaches, according to experts who participated in a recent OncLive Peer Exchange program.

Led by moderator A. Keith Stewart, MB ChB, the panel of clinical and research experts discussed strategies for defining and treating multiple myeloma, and described anticipated changes in the treatment paradigm during a Peer Exchange session entitled “Treatment of Multiple Myeloma.”

Two or Three-Drug Regimens

The optimal treatment of multiple myeloma incorporates the administration of three medications, rather than two, in most transplant-eligible patients, noted James R. Berenson, MD.

However, clinical trials, including large international studies (FIRST, UPFRONT, and MOVE), have demonstrated efficacy with two-medication regimens, such as lenalidomide and dexamethasone and bortezomib-based regimens, noted Sundar Jagannath, MD. On this basis, Jagannath stated that it is difficult to only recommend the use of a three-medication regimen.

James R. Berenson, MD

James R. Berenson, MD

In his practice, Jagannath administers bortezomib, lenalidomide, and dexamethasone, explaining that, “My principle is that you’re exposing the patient to one proteasome inhibitor, one immunomodulatory, one steroid. You want to give all classes of drug because multiple myeloma has multiple clones, and so you want to be able cover most of the clone especially in the newly diagnosed first time treatment.”

Emerging Agents and Treatment Approaches

Ixazomib

Proteasome inhibitors as a class are going to be an integral part of myeloma therapy for decades to come, said Shaji Kumar, MD.

Dr. Sundar Jagannath

Sundar Jagannath, MD

“A big challenge at the moment is that patients must travel to the clinic to receive an infusion or subcutaneous injection,” said Kumar. “The ability to give something orally would certainly change the paradigm in the disease, now that we can develop very effective oral route combinations, especially since the proteasome/immunomodulatory combinations are probably one of the most effective regimens.”

Ixazomib is the first oral proteasome inhibitor in clinical trials and was granted orphan drug designation in multiple myeloma in the United States and Europe in 2011. The drug has been studied in the relapse setting as a single agent and has been shown to be active in patients who had previously received bortezomib, said Kumar, a leading investigator in ixazomib. In one study, the combination of ixazomib with lenalidomide and dexamethasone demonstrated a 90% response rate, including a 60% very good partial response rate, among newly diagnosed patients.1

It was well tolerated, with skin rash and gastrointestinal side effects.

In the international, double-blind, placebo-controlled, phase III, TOURMALINE-MM1 trial, 722 adult patients with relapsed and/or refractory multiple myeloma were randomized to receive ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone.

Though no specific data have been disclosed, the interim analysis, reported in February 2015, found that the primary endpoint of improvement in progression-free survival (PFS) was met.2

Elotuzumab

Elotuzumab is a monoclonal antibody that targets the SLAMF7 receptor, which is present on the surface of almost all plasma cells. It is the first monoclonal antibody to show success in clinical trials in multiple myeloma. As a single agent in refractory multiple myeloma, elotuzumab induced stabilization of disease. However, when combined with lenalidomide and low-dose dexamethasone, there was an 80% response rate,3 with a durability and survival benefit that “was really quite striking,” said Sagar Lonial, MD.


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