Previously Treated Myeloma: Making Sense of Plethora of New Options

Published: Monday, Dec 12, 2016
Rafael Fonseca, MD

Rafael Fonseca, MD

Multiple myeloma has seen significant treatment advances over the past decade. In 2015 alone, the FDA approved 5 new agents or regimens for previously treated patients. Many of these agents were the first of their kind approved in this setting, making for a truly record-breaking year. Approvals included panobinostat (Farydak), the first histone deacetylase inhibitor; daratumumab (Darzalex) and elotuzumab (Empliciti), the first monoclonal antibodies for the tumor type; a new carfilzomib (Kyprolis) combination regimen; and ixazomib (Ninlaro), the first oral proteasome inhibitor.

There is no doubt that these approvals are enabling people with multiple myeloma to live significantly longer, but determining how to best use them in clinical practice remains a challenge. The treatment options for previously treated multiple myeloma are abundant; the latest National Comprehensive Cancer Network (NCCN) Guidelines include 18 preferred regimens and 11 other regimens, many of which are category 1(Table).1

During a recent OncLive Peer Exchange panel titled “New Therapeutic Approaches for Multiple Myeloma,” experts in the field sought to make sense of the enhanced treatment terrain.

“I think we can go through anecdotes, each one of us, why in specific circumstances each of [our available] agents is going to be useful,” said Rafael Fonseca, MD. “All of what we’re discussing are real-world reasons why we may go with one versus another, and I think those real-world reasons are fundamental in how we choose different regimens for our patients.”

Deciding on Treatment

Although numerous factors can be considered in deciding treatment, including logistical and insurance factors, preferences, comorbidities, and toxicity profiles, the panelists agreed that a major factor in treatment selection for all patients with relapse is the type of relapse.

Patients can have slow, indolent relapses or aggressive relapses. In the setting of aggressive relapse, the consensus was that more powerful therapies need to be used, such as carfilzomib. In contrast, they suggested that indolent relapses enable more flexibility in approach, including watch and wait until symptoms manifest, rather than treating upon observing biochemical progression; initiating more indolent treatments, such as an elotuzumab-based regimen; or proceeding with aggressive treatment, such as a carfilzomib-based therapy.

Elotuzumab and Daratumumab

For patients with a relapse that is slow and indolent, “there’s a unique opportunity to incorporate elotuzumab, which targets SLAMF7 expressed on plasma cells as well as NK cells,” said Jatin P. Shah, MD. “One of the exciting things about targeting an immune-stimulating component, the NK cells, is that you potentially can get long-term disease control.”

Elotuzumab is approved in combination with lenalidomide and dexamethasone, an antiangiogenic agent and a corticosteroid, respectively, for patients who previously received 1 to 3 prior medications.2 Approval was based on a trial that showed a progression-free survival (PFS) of 19.4 months for elotuzumab plus lenalidomide and dexamethasone versus 14.9 months for lenalidomide and dexamethasone alone. Additionally, more patients receiving elotuzumab had complete or partial tumor shrinkage (78.5% vs 65.5%).2

However, the trial did not include patients who relapsed after lenalidomide maintenance. “We really don’t know how true lenalidomide-refractory patients would do by adding in elotuzumab,” said William I. Bensinger, MD, who explained he would only consider it for patients who previously responded to lenalidomide.

The other recently approved monoclonal antibody, daratumumab, which targets the CD38 surface protein on myeloma cells, generated considerable excitement among the panelists. “If I’m going to talk about daratumumab, I’m going to say, ‘hang on to your seats,’ because it’s going to revolutionize how we treat myeloma,” said Fonseca.

Unlike elotuzumab, daratumumab can be used alone or in combinations with bortezomib/ dexamethasone or lenalidomide/dexamethasone in patients who have received previous lines of therapy.1 On November 21, the FDA approved both triplet regimens in the relapse setting following at least 1 prior therapy.

“The bottom line is that it works very well... particularly the combinations are quite impressive,” said Fonseca, noting that the depth of response in patients who have not previously responded to any agents sets it apart. He anticipates that daratumumab will move into the frontline setting.

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