Combination Therapies Change Landscape For Relapsed Myeloma

Combination Therapies Change Landscape For Relapsed Myeloma

Despite dramatic progress in the treatment of newly diagnosed myeloma, a majority of patients relapse after first-line therapy, and survival probability decreases with each subsequent new regimen. In the last 2 years, two randomized phase III trials, PANORAMA-1 and ASPIRE have demonstrated improved response rates in patients with relapsed and refractory myeloma. The regimen of carfilzomib plus lenalidomide and dexamethasone used in ASPIRE achieved progression-free survival (PFS) of 26 months.

This result is a new standard for progression-free survival in relapsed and refractory myeloma, said Jeffrey Lee Wolf, MD, of the University of California, San Francisco. Dr. Wolf was a discussant during the Tuesday, June 2, Myeloma Oral Abstract Session.

The session included abstracts on two recent phase III trials, ELOQUENT-2 and ENDEAVOR, that have “yet again introduced new options for patients whose disease has relapsed with one, two, or three prior lines of therapy,” Dr. Wolf said.

The ELOQUENT-2 trial, presented by Sagar Lonial, MD, of the Winship Cancer Institute, Emory University School of Medicine, found that adding the antibody elotuzumab to lenalidomide and dexamethasone improved overall response rate (ORR) and PFS (Abstract 8508).

Results of the ENDEAVOR trial were presented by Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens, Greece (Abstract 8509). Patients who received the proteasome inhibitor carfilzomib at twice the dose approved by the U.S. Food and Drug Administration (56 mg/m2 compared with 27 mg/m2) with dexamethasone had a median PFS of 18.7 months, whereas patients who received the standard-of-care bortezomib with dexamethasone had a median PFS of 9.4 months (hazard ratio [HR] 0.53, 95% CI [0.44, 0.650]; p < 0.0001). Carfilzomib was also superior to bortezomib in ORR (77% vs. 63%, respectively) and complete response (13% vs. 6%, respectively).

Dr. Meletios A. Dimopoulos

The carfilzomib arm demonstrated superior PFS to the bortezomib arm within different subgroups, including age and Eastern Cooperative Oncology Group performance status, and regardless of whether the patients had received prior bortezomib treatment.

Although the rates of serious adverse events were higher in the carfilzomib group (48%) than the bortezomib group (36%), the rates of discontinuation because of these events were similar between the groups (14% vs. 16%, respectively).

Dr. Wolf said that the high incidence of peripheral neuropathy in the bortezomib arm (52%) could be explained by the twice-a-week infusion schedule and administration by IV bolus. Likewise, the high rates of dyspnea (29%), cardiac events (8% cardiac failure rate), and hypertension (25%) in the carfilzomib arm were not surprising. Notably, the rates of these adverse events were similar to rates reported at the lower dose of carfilzomib (27 mg/m2) in the ASPIRE trial.

The ENDEAVOR trial included 929 patients, making it “one of the largest performed trials in patients with multiple myeloma,” Dr. Dimopoulos said.

Drug combinations studied in ENDEAVOR and ELOQUENT-2, together with results of ASPIRE and PANORAMA-1, represent the “new landscape of myeloma therapy,” Dr. Wolf said, “but at what cost?” The cost per month of treatment with carfilzomib or elotuzumab is much higher than that of treatment with bortezomib based on wholesale acquisition costs, which does not take into account many other factors, including the cost of infusion.

Watch the session: Visit the ASCO Virtual Meeting website