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
Greater understanding of tumor biology has also enabled the use of novel treatment combinations and spurred new drug development, particularly as more cytogenetic abnormalities have been discovered.2
The heterogeneity of multiple myeloma has led the National Comprehensive Cancer Network to recommend risk-adapted approaches that individualize treatments to improve patient outcomes.2 OncLive®
convened a Peer Exchange®
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.
In contrast, patients with more severe disease often require a quick response. “I think if there’s a patient who presents in extremis, in acute renal failure, then the rapidity of the reduction of the disease burden is important,” said Ivan M. Borrello, MD, who acknowledged those presentations are rare. “[In most patients], if the trend is going in the right direction, I think [we can] deliver therapy with potentially less intensity and less toxicity over a longer period of time,” he said.
Frontline therapy choices among the panelists varied based on patient factors and institutional practices, but all panelists reported using combination regimens, with most incorporating bortezomib (Velcade) and lenalidomide (Revlimid) into their protocols, preferring 3-drug regimens for younger, more fit patients, and 2-drug regimens for older and more frail patients. “For the transplant-eligible patient, our upfront regimen of choice is bortezomib with lenalidomide and dexamethasone. For the older, truly frail patient, it’s probably lenalidomide and dexamethasone. And now there may be talk about an antibody there,” said Sagar Lonial, MD, FACP. Although 2-drug regimens were generally regarded as safest for less robust patients, Borrello said his institution has used 3-drug regimens in some elderly populations, although at lowerdose intensities.
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.
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.