Maintenance ixazomib extends PFS for subset of patients with multiple myeloma
First-line maintenance therapy with ixazomib extended PFS compared with placebo among certain patients with newly diagnosed multiple myeloma, according to results of the TOURMALINE-MM4 trial published in Journal of Clinical Oncology.
“So far, lenalidomide [Revlimid, Bristol Myers Squibb] is the only approved drug for continuous treatment of newly diagnosed patients with multiple myeloma not eligible for autologous stem cell transplantation. However, this agent may have some long-term side effects and may be less active in subsets of patients such as those with International Staging System stage 3 [disease] or with abnormal cytogenetics. Thus, new agents are needed for these patients,” Meletios A. Dimopoulos, MD, professor in the department of clinical therapeutics at National and Kapodistrian University of Athens School of Medicine and Alexandra General Hospital in Greece, told Healio. “Our study has shown that maintenance therapy with the oral proteasome inhibitor ixazomib [Ninlaro, Takeda] was superior to placebo in patients with symptomatic myeloma, who responded to first-line therapy and did not undergo autologous stem cell transplantation.”
The randomized, phase 3, double-blind, placebo-controlled trial included 706 patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation who achieved at least a partial response after 6 to 12 months of standard induction therapy.
Investigators randomly assigned patients to ixazomib (n = 425) or placebo (n = 281) on days 1, 8 and 15 of 28-day cycles as first-line maintenance for 2 years.
Patients in the ixazomib and placebo groups had similar baseline characteristics, including median age (72 years vs. 73 years), sex (men, 52.2% vs. 55.2%) and race (white, 77.6% vs. 80.8%).
PFS since time of randomization served as the primary endpoint.
Median follow-up was 21.1 months.
Results showed a 34.1% reduction in the risk for progression or death with ixazomib vs. placebo (HR = 0.65; 95% CI, 0.54-0.8). Median PFS since randomization was 17.4 months (95% CI, 14.8-20.3) in the ixazomib group compared with 9.4 months (95% CI, 8.5-11.5) in the placebo group.
In addition, researchers observed a statistically significant improvement in PFS with ixazomib since randomization among the prespecified subgroups of patients who achieved a complete response or very good partial response with initial therapy (median PFS, 25.6 months vs. 12.9 months; HR = 0.58; 95% CI, 0.44-0.76).
Ixazomib also conferred PFS benefits among patients with International Staging System stage 3 disease (HR = 0.69; 95% CI, 0.49-0.96) and those aged 75 years or older (HR = 0.73; 95% CI, 0.53-1).
At the time of data cutoff, 16% of patients in the ixazomib group and 10.1% of patients in the placebo group had completed all protocol-specified treatment cycles.
A higher percentage of patients in the ixazomib vs. placebo group experienced grade 3 or higher treatment-emergent adverse events (36.6% vs. 23.2%) and discontinued treatment because of these events (12.9% vs. 8%). The most common any-grade treatment-emergent adverse events included nausea (26.8% vs. 8%), vomiting (24.2% vs. 4.3%) and diarrhea (23.2% vs. 12.3%).
No increase in new primary malignancies occurred with ixazomib vs. placebo (5.2% vs. 6.2%) and rates of on-study mortality were similar between the groups (2.6% vs. 2.2%).
Data on PFS2 and OS had not matured by data cutoff. The study remains blinded and follow-up continues, according to the researchers.
“Our study showed for the first time that ixazomib is an active agent in this patient setting. Ixazomib can be used in patients who cannot tolerate long-term maintenance therapy with lenalidomide,” Dimopoulos said. “The benefit of ixazomib maintenance is modest. Thus, the agent should be investigated in the future as part of a combination therapy in the maintenance strategies of patients with multiple myeloma.”
For more information:
Meletios A. Dimopoulos MD, can be reached at Alexandra General Hospital, 80 Vasilisis Sophias, 11528, Athens, Greece; email: mdimop@med.uoa.gr.
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