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Four Major Developments in Multiple Myeloma: ASH 2018

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Frontline Monoclonal Antibody Therapy for Multiple Myeloma

The first is the move toward monoclonal antibody therapy in frontline multiple myeloma. Earlier this year, the US Food and Drug Administration (FDA) approved daratumumab in combination with bortezomib, melphalan, and prednisone in patients who were ineligible for an autologous stem cell transplant, based on a clinical trial that demonstrated its superiority over just melphalan, prednisone, and bortezomib together.

Here at the annual meeting, the late-breaking abstract being presented is looking at daratumumab/lenalidomide/dexamethasone versus lenalidomide/dexamethasone alone.[1] This is a large phase 3 trial that will very likely lead to the use of more daratumumab frontline.

In patients you are treating now with bortezomib/lenalidomide/dexamethasone—or in some cases, just lenalidomide/dexamethasone—we are quite likely going to see in the very near future the addition of daratumumab. This is significant, of course, because we have known that monoclonal antibodies pair very well with just about every myeloma treatment we have. Now we are going to see their use upfront as we try to have a deeper and a more durable response in our patients.

More Approvals for Myeloma

The second major movement looks to two other FDA approvals. The monoclonal antibody elotuzumab, which was previously approved for use in relapsed multiple myeloma with lenalidomide, has now been approved in combination with pomalidomide. We have shrinking options after patients have had two or three relapses. This combination of elotuzumab plus pomalidomide really enhances the activity of just pomalidomide alone and provides another option.[2]

The other FDA approval recently was for carfilzomib. We have been using carfilzomib for many years as a single agent or with dexamethasone, and in combination with lenalidomide or other agents, but now we can actually use the agent once weekly. The ARROW study compared twice-weekly with once-weekly carfilzomib and, interestingly, not only did it demonstrate equivalence, but weekly dosing of 70 mg/m2 demonstrated an improved response rate and improved progression-free survival, while at the same time not increasing toxicity.[3]

In my practice, I have almost exclusively gone to using weekly carfilzomib because it is more convenient for the patient and indeed is more efficacious.

Triple-Refractory Disease

The third movement has to do with the space of patients who we often call “triple refractory.” These are patients who have seen a monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug, and often have seen multiples of those three classes but are now progressing.

GDMeds, an India Pharmacy Service company

 

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