Lenalidomide, Dexamethasone New Standard in Transplant-Ineligible Myeloma

July 5, 2016

Continuous lenalidomide plus low-dose dexamethasone reduced the risk for progression in untreated multiple myeloma patients who were ineligible for stem cell transplantation.

Continuous treatment with lenalidomide plus low-dose dexamethasone (Rd) significantly reduced the risk for progression from untreated multiple myeloma compared with melphalan, prednisone, and thalidomide (MPT) among patients who were ineligible for stem cell transplantation, according to the results of the phase III FIRST trial published in the Journal of Clinical Oncology.

This continuous treatment regimen even improved risk for progression or death among patients in the trial aged 75 years or older.

“This extended follow-up and subanalysis of the FIRST trial establishes continuous treatment with Rd until disease progression as a new standard of care for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation, regardless of age,” wrote researcher Cyrille Hulin, MD, of Bordeaux Hospital University Center in Bordeaux, France, and colleagues. “With proper monitoring and dose adjustment, Rd continuous is an effective and tolerable treatment option for even the most elderly patients.”

According to the study, there is limited information available about the use of lenalidomide in patients aged older than 75 years with newly diagnosed multiple myeloma. The FIRST trial was designed to compare the efficacy of lenalidomide-containing regimens with a more standard treatment of MPT.

The study included 1,623 patients with untreated but symptomatic multiple myeloma. Patients were randomly assigned to lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous; n = 535), the same regimen for 72 weeks (Rd18; n = 541), or MPT (n = 547). The primary endpoint was progression-free survival (PFS). Thirty-five percent of patients in the study were 75 years old or older.

Patients assigned to continuous Rd had significantly longer PFS compared with patients assigned to MPT, with a 31% reduction in the risk for progression or death (hazard ratio [HR], 0.69 [95% CI, 0.59–0.80]; P < .001). Among patients aged 75 or younger there was a 36% decreased risk for progression (P < .001) compared with a 20% risk reduction in patients aged older than 75 (P = .084). Results with the Rd18 regimen were similar to those of the MPT regimen.

The researchers noted that Rd continuous extended PFS vs MPT in patients both 75 years or younger and older than 75 years. “However, in patients aged older than 75 years, this benefit was not reflected by medians, which were similar across treatment arms, even though the risk of progression or death with Rd continuous was reduced by 22% and 20% vs Rd18 and MPT, respectively, and 4-year PFS with Rd continuous was more than double that with Rd18 and MPT.”

Rd continuous also significantly improved overall survival, with a 10-month increase in median overall survival compared with MPT (58.9 vs 48.5 months; HR, 0.75 [95% CI, 0.62–0.90]). This improvement was even greater among patients older than 75 years (52.3 vs 37.8 months; HR, 0.72 [95% CI, 0.54–0.96]).

“In line with PFS results, Rd continuous treatment also extended duration of response and time to second-line antimyeloma therapy for older and younger patients,” the researchers wrote. “Overall response rate with fixed-duration Rd18 was comparable to that with Rd continuous and greater than that with MPT, but PFS with Rd18 was similar to that seen with MPT, suggesting that the major benefits of Rd continuous treatment are derived from the prolonged duration of first-line therapy.”

Regardless of age, patients experienced similar rates of grade 3 to 4 treatment-emergent adverse events. However, the researchers noted that older patients required more frequent lenalidomide dose reductions.