Sagar Lonial, MD
The data being amassed about novel multiple myeloma therapies have the potential to change the way patients with relapsed or refractory disease are currently being treated, according to experts who participated in a recent OncLive
Peer Exchange® program.
The investigational monoclonal antibodies elotuzumab and daratumumab are generating hopes that combining these agents with existing drugs would improve outcomes. Evidence is growing that carfilzomib represents an advanced proteasome inhibitor that may provide further benefit if employed with a higher dosage. And, the histone deacetylase (HDAC) inhibitor panobinostat appears effective even in high-risk populations as part of an all-oral regimen.
These were among the topics discussed by a panel of multiple myeloma experts during the Peer Exchange roundtable, entitled “Emerging Concepts in the Treatment of Multiple Myeloma.” The discussions focused on data presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting convened in June.
Sagar Lonial, MD, a leading investigator into the emerging monoclonal antibodies, served as moderator of the discussion, which covered a wide range of topics. The panelists agreed that much work remains to be done in the field to determine how best to combine emerging agents with immunomodulatory (IMiD) drugs and other currently available therapies.
Monoclonal Antibodies Stir Excitement
Some of the most exciting data in future myeloma treatment that were presented at ASCO involved elotuzumab and daratumumab, which both have applications pending under the FDA’s priority review program.
Elotuzumab is being evaluated in combination with lenalidomide and dexamethasone for patients who have relapsed after one or more prior therapies; daratumumab is under review as monotherapy for patients who have failed at least three lines of prior therapy or who are double refractory to a proteasome inhibitor and an IMiD.
The phase III ELOQUENT-2 trial showed that more patients with relapsed/refractory multiple myeloma responded to lenalidomide and dexamethasone combined with the monoclonal antibody elotuzumab (79%) compared with lenalidomide and dexamethasone alone (66%). In addition, the triplet combination resulted in a progression-free survival (PFS) benefit of almost 5 months, as well as an approximately 30% reduction in the risk of progression.1
Noopur Suresh Raje, MD
“I think this is a new milestone in myeloma, and if you think about monoclonal antibodies, I think we can learn something from our lymphoma colleagues,” said Noopur Suresh Raje, MD, director, Multiple Myeloma Program, Massachusetts General Hospital. “Rituximab is generally slapped on to whatever backbone treatment they have, and the good news with monoclonal antibodies [is that] once we’re able to manage those infusion-related reactions, we can piggyback these monoclonal antibodies on any kind of combination approach that we’re using in myeloma.”
Jatin J. Shah, MD, associate professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, noted that rituximab was a “major step forward” in lymphoma that specialists were able to deploy widely. In contrast, Shah said, myeloma specialists likely will have more than one novel antibody to launch into clinical practice in the same time frame and it will be challenging to figure out how best to use each drug.
Jatin J. Shah, MD
While elotuzumab targets signaling lymphocytic activation molecule F7 (SLAMF7), daratumumab targets CD38. In a phase II trial of patients who were heavily pretreated, daratumumab monotherapy resulted in a PFS of 3.7 months, with nearly 30% of patients responding and a duration of response of 7.4 months.2
Lonial, chief medical officer, Winship Cancer Institute, Emory University School of Medicine, said some of the responses seen in this trial were stringent complete responses (CRs), which he found “quite striking” considering that the participants had received a median of five prior lines of therapy, including carfilzomib and pomalidomide as well as other drugs.