Aprepitant Reduced Chemo-Induced Emesis in Multiple Myeloma

Patients with multiple myeloma treated with high-dose melphalan prior to undergoing autologous transplantation had significant reductions in chemotherapy-induced nausea and vomiting, and improvements in quality of life when they were administered aprepitant in addition to a standard preventive regimen of granisetron and dexamethasone.

“For patients undergoing high-dose melphalan conditioning, addition of aprepitant to a standard antiemetic regimen should be strongly considered,” wrote Thomas Schmitt, MD, of Heidelberg University Hospital, Heidelberg, and colleagues in the Journal of Clinical Oncology.

Aprepitant is a neurokinin-1 antagonist, a drug class shown to improve control of both acute and delayed emesis, which can be particularly significant in patients with multiple myeloma undergoing treatment with high-dose melphalan.

Schmitt and colleagues conducted this phase III trial in which 362 patients were randomly assigned to aprepitant 125 mg on day 1 and 80 mg on days 2 to 4, granisetron 2 mg on days 1 to 40, and dexamethasone 4 mg on day 1 and 2 mg on days 2 to 3, or placebo, matching granisetron, and dexamethasone 8 mg on day 1 and 4 mg on day 2 to 3. All patients were administered melphalan on days 1 to 2 before undergoing transplant on day 4.

Reports of emesis within 120 hours of melphalan administration were significantly lower among those patients assigned aprepitant than those assigned the standard regimen in both the intent-to-treat analysis (58% vs 41%; OR = 1.92; 95% CI, 1.23-3.00; P = .0042) and the per-protocol analysis (59% vs 39%; OR = 2.16; 95% CI, 1.30-3.60; P = .003).

“The majority of patients excluded from the per protocol analysis did not receive the melphalan infusion within the required timeframe after intake of study medication,” the researchers wrote. “Thus, it can be speculated that suboptimal drug plasma levels at least influenced rates of acute chemotherapy-induced nausea and vomiting. However, the overall effect seemed negligible.”

During the delayed phase of treatment (24 to 120 hours post) 60% of patients assigned aprepitant reported no emesis or additional antiemetic treatment compared with 46% of patients on the standard regimen (OR = 1.80; 95% CI, 1.15-2.85; P = .011).

Similar positive results for aprepitant were seen for the prevention of major nausea (94% vs 88%; P = .026) and absence of emesis (78% vs 65%; P = .0036) within 120 hours of melphalan administration. No significant differences were found between the two regimens for the effect on overall nausea. 

The researchers also examined quality-of-life outcomes using a questionnaire. Results indicated that 74% of patients assigned aprepitant reported no impact on daily life compared with 59% of patients on the standard regimen (P = .004).

“To our knowledge, this is the largest prospective, randomized phase III trial assessing this question,” the researchers wrote. “The combination regimen resulted in a significant reduction of major nausea and emesis.”