Researchers have demonstrated in a phase II study, the efficacy of novel treatments for newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation.
Meletios A. Dimopoulos, MD, from the National and Kapodistrian University of Athens, School of Medicine, Athens, Greece, in collaboration with other international research centers studied investigational proteasome inhibitor (PI) ixazomib to evaluate the success of combining with cyclophosphamide and dexamethasone (ICd) as frontline treatment for multiple myeloma.
The results (abstract 26) were presented at the American Society of Hematology's 57th Annual Meeting in Orlando, Fla., December 5, 2015.
Patients with functioning hematologic, hepatic, and renal systems were included in the study, although this study population was ineligible for transplant due to age or other comorbidities. Dr. Dimopoulos and colleagues randomly assigned 70 patients 1:1 to receive up to 13 (28-day) cycles of induction therapy with ixazomib 4 mg orally on days 1, 8, and 15, plus cyclophosphamide 300 mg/m2 (ICd-300 arm) or 400 mg/m2 (ICd-400 arm) orally on days 1, 8, and 15, plus dexamethasone 40 mg orally (20 mg in patients older than 75 years) on days 1, 8, 15, and 22. Toxicities were a concern, but patients in each arm were evaluated after the first cycle, and they tolerated the treatments well.
According to the study, the primary endpoint was the combined rate of complete response plus very good partial response (CR+VGPR). Secondary endpoints included overall response rate (ORR; CR+VGPR+ partial response [PR]) and safety (adverse events [AE]).
Response rates were assessed by the investigators at the end of each cycle. Of the 70 stage II/III study participants, CR+VGPR rates across all 13 cycles were 27% (ICd-300) and 23% (ICd-400); ORRs were 80% and 73%, respectively. Patients received a median of 6 cycles in the ICd-300 arm and 6.5 cycles in the ICd-400 arm.
Most common AEs (>15% all pts) were anemia (19% [ICd-300] and 29%[ICd-400]), neutropenia (17% and 32%), nausea (14% and 24%), peripheral neuropathy (PN; 17% and 21%), diarrhea (19% and 15%), vomiting (14% and 21%), constipation (17% and 15%), and fatigue (14% and 18%). Most common grade 3/4 AEs were neutropenia (14% and 32%), anemia (11% and 15%), and pneumonia (8% and 9%).
While researchers reported high response rates in both the ICd-300 and ICd-400 arms, toxicity rates appeared higher with ICd-400 arm, suggesting that ICd-300 may be a more preferable regimen for older patients. But the overall toxicity was manageable.
The research team concluded that the triplet treatment of ICd is tolerable in transplant-ineligible patients with newly diagnosed multiple myeloma.