Current and Prospective Therapies Are Improving Outcomes in Relapsed Multiple Myeloma

Thomas G. Martin, MD

During the past decade, there have been dramatic improvements in outcomes for patients with multiple myeloma, with many more achieving an increased depth of response, complete remissions, and longer progression-free survival (PFS) and some even being cured. However, the majority of patients ultimately relapse, which continues to pose a significant challenge.

During a recent OncLive Peer Exchange®, a panel of experts on multiple myeloma discussed new agents and combinations that are improving the care of patients with relapsed multiple myeloma and reviewed strategies for treating these patients when they develop drug resistance, which is a common problem that often occurs early in the disease course and limits therapeutic options.1 They also discussed recent data for some investigational treatments generating considerable excitement in the field, including chimeric antigen receptor (CAR) T-cell therapy and novel selective inhibitors.

Treatment Approaches

Until recently, the standard treatment for relapsed multiple myeloma has been lenalidomide (Revlimid) plus dexamethasone (Rd) or bortezomib (Velcade) plus dexamethasone (Vd).1 However, many new agents have been recently approved for relapsed disease, including carfilzomib (Kyprolis), ixazomib (Ninlaro), panobinostat (Farydak), elotuzumab (Empliciti), daratumumab (Darzalex), and pomalidomide (Pomalyst).1Results from recent randomized studies have shown greater benefit with a triplet regimen that adds 1 of these newer agents to Rd or Vd.1,2

“In studies that included patients who received 1 to 3 prior lines of therapy, daratumumab/ bortezomib/dexamethasone (DVd), daratumumab/lenal idomide/dexamethasone (DRd), and carfilzomib/lenalidomide/ dexamethasone (KRd) have shown significant advantage,” Thomas G. Martin, MD, said. Martin explained that he uses DVd, DRd, or KRd at first relapse because he tries to be aggressive in his approach, especially when patients are young or can otherwise tolerate it. Currently, DVd, DRd, and KRd are National Comprehensive Cancer Network (NCCN)–preferred regimens with a category 1 recommendation for previously treated multiple myeloma. 2 On November 6, the FDA added another triplet therapy to the mix. The agency approved elotuzumab for use in combination with pomalidomide and low-dose dexamethasone for the patients with relapsed/refractory multiple myeloma following 2 or more prior therapies, including lenalidomide and a proteasome inhibitor (PI). A significant challenge, however, is that many patients become resistant to lenalidomide and bortezomib early in their disease course because these agents are also used in the frontline.1

Lenalidomide Resistance

The panelists discussed different strategies for treating patients who develop lenalidomiderefractory disease. A key decision is whether to switch immunomodulatory drugs (IMiDs; ie, replace lenalidomide with pomalidomide) or to switch to a regimen that does not include an immunomodulatory agent (eg, carf ilzomib/dexamethasone [Kd] or DVd).

Martin said he would probably use DVd in these patients but would consider using daratumumab/pomalidomide/ dexamethasone if patients’ complete blood cell counts do not pose a problem, although he prefers saving pomalidomide for subsequent lines.

Ajai Chari, MD, said that while a regimen with a bortezomib backbone could be considered, he, too, prefers a regimen that incorporates daratumumab. He said that he selects the partner drug based on the patient. “I would favor daratumumab with pomalidomide if they have no history of thrombotic events and good blood counts. If they’re t(4;14), maybe [daratumumab] with carfilzomib or with bortezomib,” he said. “Luckily, we have so many combinations to pick from.”

However, Sagar Lonial, MD, FACP, thought that the efficacy of pomalidomide as a partner drug in patients with t(4;14) or 17p deletion is undervalued. “In 17p, it actually looks as good as any other drug that’s out there. So daratumumab/ pomalidomide/dexamethasone for that reason is our go-to in the first salvage. And I’ve been really struck by the t(4;14)s and how well they’ve responded after having short responses to either carfilzomib or bortezomib,” he said.

During the past decade, there have been dramatic improvements in outcomes for patients with multiple myeloma, with many more achieving an increased depth of response, complete remissions, and longer progression-free survival (PFS) and some even being cured. However, the majority of patients ultimately relapse, which continues to pose a significant challenge.

During a recent OncLive Peer Exchange®, a panel of experts on multiple myeloma discussed new agents and combinations that are improving the care of patients with relapsed multiple myeloma and reviewed strategies for treating these patients when they develop drug resistance, which is a common problem that often occurs early in the disease course and limits therapeutic options.1 They also discussed recent data for some investigational treatments generating considerable excitement in the field, including chimeric antigen receptor (CAR) T-cell therapy and novel selective inhibitors.
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