ASH Clinical News ACN_5.4s_March_supplement_web - Page 20

MEETING NEWS regardless of prior rituximab therapy, age, race, time since last therapy or tumor burden. Median duration of response was longer in the R2 group, as well (36.6 months vs. 21.7 months; HR=0.53; 95% CI 0.36-0.79; p=0.0015). When asked about where R2 fits in the landscape of relapsed FL, Dr. Leonard noted that, although there are several other agents approved for recurrent FL, including single-agent ritux- imab, “our data suggest that many patients could instead benefit from the combination of R2.” However, the trial was not designed to compare R2 with other regimens containing chemotherapy and other agents, and these decisions “depend on individual patient situations,” he added. As a limitation of the study, Dr. Leonard noted that the trial pop- ulation included a small number of patients with MZL, which may limit the results’ generalizability to patients with MZL. The authors report relationships with Celgene, the manufac- turer of lenalidomide, which sponsored the trial. REFERENCE Leonard JP, Trněný M, Izutsu K, et al. AUGMENT: A phase III randomized study of lenalidomide plus rituximab (R2) vs rituximab/placebo in patients with relapsed/ refractory indolent non-Hodgkin lymphoma. Abstract #445. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San Diego, CA. Evaluating Ixazomib Regimens in Patients With Newly Diagnosed Myeloma Two studies presented at the 2018 ASH Annual Meeting explored the use the oral proteasome inhibitor (PI) ixazomib in patients with newly diagnosed multiple myeloma (MM). The first eval- uated its efficacy as maintenance therapy for patients who underwent post-autologous hematopoietic cell transplantation (AHCT) and the second examined the feasibility and efficacy of an ixazomib and daratumumab combination as induction therapy. Ixazomib Maintenance For the substantial portion of patients with MM who relapse following AHCT, maintenance therapy with ixazomib could offer a new treatment option to delay disease progression and extend survival, according to results from the phase III, double-blind, placebo-controlled, multicenter TOURMALINE-MM3 trial. 1 The drug also was associated with deeper responses, while maintaining a “favorable” safety profile, lead author Meletios A. Dimopoulos, MD, from the National and Kapodistrian University of Athens School of Medicine in Greece, said during his presentation. While lenalidomide is a commonly used post-AHCT main- tenance therapy, Dr. Dimopoulos noted that nearly one-third of patients discontinue the drug due to toxicity. However, as an oral PI, ixazomib has a less frequent administration and has been shown to have manageable toxicity. “We think that these findings show ixazomib to have a very good therapeutic value,” he added. The TOURMALINE-MM3 trial enrolled 656 adult patients with newly diagnosed MM who had received standard of care with a PI or immunomodulatory drug (IMiD) prior to undergoing a single AHCT with high-dose melphalan. Eligible patients had experienced at least a partial response to AHCT; those whose disease relapsed, were unresponsive to frontline therapy, or underwent a tandem AHCT or received post- AHCT consolidation therapy were excluded from the analysis. Patients were stratified based on induction protocol, pre- induction International Staging System (ISS) stage disease, and response following AHCT, then randomized 3:2 to receive either weekly ixazomib (n=395) or matched placebo (n=261). Ixazomib 18 Focus on Lymphoid Malignancies 3 mg was administered on days 1, 8, and 15 of 28-day cycles for two years or until disease progression or unacceptable toxicity, up to 26 cycles. If patients tolerated ixazomib 3 mg during the first four cycles, dose was increased to 4 mg (n=317 in the ixazomib group and n=222 in the placebo group). Participants’ median age was 58 years; “however, 15 percent of patients were older than 65 years,” Dr. Dimopoulos noted. Nearly one-fifth of patients in each group had high-risk cytogenetics. Other baseline characteristics were similar between the treat- ment groups: Most patients in each group (59%) had induction therapy with a PI, while 11 percent in each group received an IMiD and 30 percent in each group received both agents. Also, a similar portion of patients in each group had achieved minimal residual disease (MRD)–negative status (33% for both). Most patients had experienced a very good partial response (VGPR) following AHCT (45% in the ixazomib arm and 44% in the placebo arm), and approximately one-third in each group had a complete response (CR; 33% and 36%, respectively). As of April 16, 2018 (data cutoff), the median duration of treatment at 4 mg was 15.2 months (range = 0-22 months) in the ixazomib arm and 16.6 months (range = 0-21 months) in the placebo group. Results from the primary endpoint analysis showed that maintenance treatment with ixazomib prolonged median PFS, compared with placebo (26.5 months vs. 21.3 months; hazard ratio [HR] = 0.72; 95% CI 0.58-0.89; p=0.002). The benefit in PFS was observed across subgroups, including: • age (≥60 years vs. <75 years): HR=0.662 ISS stage III disease: HR=0.0661 • cytogenetic risk: HR=0.625 for high risk and HR=0.648 for standard risk Patients who received maintenance therapy with ixazomib also had deeper responses, Dr. Dimopoulos noted. For example,