Multiple myeloma (MM) disproportionately affects elderly patients, and although novel agents have substantially improved MM outcome, there may be further opportunities to optimize therapy among different age strata. Researchers have evaluated the efficacy, safety, and outcome of patients included in the GEM2010 trial according to age to identify the group of patients who benefit most from this total therapy approach.
In this trial, 242 patients were randomized to receive a sequential scheme consisting of 9 cycles of bortezomib/melphalan/prednisone (VMP) followed by 9 cycles of lenalidomide/dexamethasone (Rd) or the same regimens in an alternating approach (1 cycle of VMP alternating with 1 Rd), up to 18 cycles. VMP included the intravenous administration of weekly bortezomib at 1.3 mg/m2 in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1 to 4. Rd treatment consisted of lenalidomide 25 mg daily on days 1 to 21 plus dexamethasone 40 mg weekly.
Of 233 evaluable patients, 115 (49%) were between 65 and 75 years of age, 69 (30%) patients were between 75 and 80 years, and 49 (21%) patients were older than 80 years. The distribution of patients was well balanced between the 2 arms; there were no significant differences in the baseline characteristics of the 3 subgroups of patients.
The overall response rate (ORR) was similar in patients aged 65 to 75 and 75 to 80 years (80% and 83%), but significantly lower in patients older than 80 years (68%) (P = .007). Likewise, the complete response rate was similar in patients between 65 and 75 (45%) and 75 and 80 (49%) years, but significantly lower in those over 80 years of age (10%) (P <.0001). The difference in median progression-free survival (PFS) was statistically nonsignificant among patients aged between 65 and 75 and 75 and 80 (35 and 32 months) years; however, median PFS was 25 months in patients older than 80 years (P = .02). Seventy-five percent of patients between 65 and 75 years achieved overall survival (OS) at 4 years, compared with 60% of patients between 75 and 80 years (P = .05) and 30% of patients older than 80 years (P = .003). Hematologic and nonhematologic toxicity profiles were similar in the 3 age-groups; however, 63% of patients older than 80 years discontinued the trial early due to toxicity or informed consent withdrawal, while this occurred in only 30% of patients aged 65 to 75 and 75 to 80 years.
Investigators concluded at this time that VMP and Rd regimens for newly diagnosed elderly MM patients most likely represent the optimal therapeutic option for elderly patients between 65 and 80 years in a sequential or alternating approach. However, given the sizable drop-off in ORR, PFS, and OS for patients over 80 years of age, there may be an ongoing need to identify optimal treatment regimens best-suited to this patient population.
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