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Myeloma Paradigm Shifts With Continued Success of Combo Regimens

Gina Columbus @ginacolumbusonc
Published: Tuesday, Nov 15, 2016

Rafael Fonseca, MD

Rafael Fonseca, MD

Pivotal clinical trial findings from the past year will likely have a game-changing effect on the multiple myeloma landscape, according to Rafael Fonseca, MD. Moreover, he adds, oncologists may be looking at a future where the number of drugs in a single regimen continues to grow in an effort to further improve outcomes.

For example, in October 2016, the FDA granted a priority review designation to the monoclonal antibody daratumumab (Darzalex) in combination with lenalidomide (Revlimid) and dexamethasone or bortezomib (Velcade) and dexamethasone for patients with relapsed multiple myeloma following at least 1 prior therapy.

The designation was based on results from the phase III POLLUX1 and CASTOR2 studies.

In the POLLUX trial, the addition of daratumumab to lenalidomide and dexamethasone led to a 63% reduction in the risk of progression or death compared with lenalidomide and dexamethasone alone for patients with relapsed/refractory disease. Meanwhile, in the CASTOR study, adding daratumumab to bortezomib and dexamethasone was associated with a 61% reduction in the risk of progression or death versus bortezomib and dexamethasone alone for patients with recurrent or refractory disease.

Updated findings regarding another monoclonal antibody, elotuzumab (Empliciti), could also guide oncologists in determining the agent’s role in multiple myeloma.

Elotuzumab was approved by the FDA in November 2015 for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma following failure on 1 to 3 prior therapies. The approval was based on data from the phase III ELOQUENT-2 trial.3 Here, the triplet regimen led to a 30% reduction in the risk of disease progression when compared with lenalidomide/dexamethasone alone.

In an interview during the 2016 OncLive State of the Science Summit on Treatment of Hematologic Malignancies, Fonseca, a professor of Medicine at Mayo Clinic, discussed several of the key recent advancements in the management of multiple myeloma.

OncLive: What were the key points of your lecture on advances in multiple myeloma?

Fonseca: What I tried to accomplish is to update the audience on some of the developments that occurred over the last year with regard to clinical trials that address the treatment of the disease. We have a number of trials that have looked at frontline therapy, as well as therapy for the relapsed/refractory setting. Fortunately, we have a plethora of trials that are showing improvements in our ability to control the disease. Some of the trials that are maturing are showing improvements in overall survival.

Perhaps, most excitedly, we do have the advent of monoclonal antibodies that are now part of the standard toolbox in our treatment against myeloma. Our next order of duty is to find out how to combine all of these agents to provide optimal disease control. In the mind of many of us, [our goal] is to control myeloma

Will we ever get to a place in which patients die with, not of, myeloma?

Absolutely. The survival expectancy with myeloma continues to improve. That is not to say that it is not a serious disorder. For many patients, particularly those with high-risk disease, myeloma remains very challenging. However, more and more patients are seeing a 10-year anniversary. It’s not unusual for me to see patients who are doing 7, 8, or 9 lines of therapy now. They are still responding quite nicely to treatment.

We would like to compress that. We would certainly like to provide patients with a combination with or without transplant, and put a large number of those patients into durable remissions; some of those should translate into cures in the future. We know, from historic data, that when patients achieve a complete response (CR) after transplant, there is a subset of them—about 30%—that will remain at CR at 20 years. Now, we can put patients on stringent CRs and minimal-residual disease (MRD)¬–negative status. Our hope is that, as time goes by, more and more patients will fall into that category.

What do you look for when you are identifying patients who are high risk?

Traditionally, we have looked at high-risk disease based on the genetic markers. That can be determined in 1 of multiple ways. The standard way has been through genetic testing by FISH for abnormalities; it is very important that is done properly. If a bone marrow is sent out to a lab and they don’t have a selection of cells, there is a very high risk that the results will be false negatives.

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