Experts Discuss Strategies for Boosting Frontline Responses in Myeloma

Christina Loguidice
Published: Monday, Sep 04, 2017
Saad Z. Usmani, MD

Saad Z. Usmani, MD
During the past decade, the treatment of multiple myeloma has significantly changed, enabling more patients to achieve deep and durable responses.1,2 Several new drug classes with highly effective therapies have emerged, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and histone deacetylase inhibitors.2

panel with moderator Keith Stewart, MB, ChB, and other experts in multiple myeloma to discuss the goal of achieving deep and durable responses in more patients, including older adults who are not able to tolerate highly aggressive treatments. During the discussion, the panelists provided personal perspectives and discussed the newest information on the goals of therapy in symptomatic disease, testing for minimal residual disease (MRD), role of transplantation, and the use of maintenance therapy. “We continue to see dramatic shifts in the management of multiple myeloma,” said Stewart.

Goals of Therapy for Symptomatic Patients

The panelists agreed that the goal of therapy is to achieve MRD-negative complete remissions, but that the timeline for achieving this goal varies by patient. “For elderly patients, I think you must compromise a little bit on efficacy for the tolerability and safety…achievement of a deep response is important for these patients, but it may take a little longer than in the younger patients,” said Saad Z. Usmani, MD, FACP. This approach was supported by Thomas G. Martin III, MD who concurred that the road to a complete response (CR) can be significantly longer in older populations. “I tell them, ‘You’re going to be on therapy for, potentially, upwards of a year. Hopefully each month [the need for therapy] will go down—slowly, slowly, slowly,’” he said.

Most panelists did not routinely use carfilzomib (Kyprolis) combinations upfront, but Martin reported using it with lenalidomide and dexamethasone in younger and more fit patients and in those with high-risk cytogenetics, such as 17p deletion, t[4;14] deletion, or 1q gain. Others noted they might start using it as an upfront therapy based on emerging data. The most unique regimen was reported by Gareth Morgan, MD, FRCP, FRCPath, PhD, whose institution uses combinations with classic chemotherapy agents to enable harvesting stem cells for eventual stem cell transplantation. “We are aiming each point in the process to achieve increasing remissions— aiming for MRD negativity, ultimately,” he said.

MRD Testing

Because improved multiple myeloma treatments have led to higher CR rates, there has been a need to redefine response criteria to enable identification of deeper responses than were conventionally possible.1 This has led to the emergence of flow cytometry and, more recently, next-generation gene sequencing to identify residual tumor cells in the bone marrow.1 The panelists identified numerous pros and cons with each testing method.
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