Phase 2 Trial of the Combination of Ixazomib, Thalidomide and Dexamethasone (ITD) in Relapsed/Refractory Myeloma: Planned Preliminary Analysis

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.3265-3265
• Main Authors: Bergin, Krystal, Yuen, Flora, Wallington-Beddoe, Craig Thomas, Kalff, Anna, Sirdesai, Shreerang, Reynolds, John, Spencer, Andrew
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-118172

Introduction: Despite improved survival outcomes in multiple myeloma (MM), disease relapse is inevitable and further therapeutic options are required. Therapy with bortezomib (a proteasome inhibitor (PI)), thalidomide and dexamethasone (VTD) has been shown to be highly effective in relapsed/refractory MM (RRMM). Ixazomib (an oral PI) in combination with lenalidomide and dexamethasone (IRD) has been shown to increase progression-free survival (PFS) in RRMM. Currently there are limited data on the efficacy/tolerability of the combination of ixazomib, thalidomide and dexamethasone (ITD). ITD may prove to be an attractive “all oral” therapeutic alternative particularly in jurisdictions with less access to high cost therapeutics. Aim: To evaluate the efficacy and safety of the combination of ixazomib, thalidomide and dexamethasone (ITD) in RRMM. Methods: This is a planned preliminary analysis of a multi-centre, single arm, open label, phase 2 study of the combination of ITD in RRMM patients with 1-3 prior lines of therapy. ITD (Ixazomib: 4mg orally D1, 8, 15, Thalidomide 100mg orally nocte D1-28, Dexamethasone 40mg orally D1, 8, 15, 22 of a 28-day cycle) was continued until disease progression or unacceptable toxicity. We plan to enrol 45 patients and to date data for 33 patients who have received 4 cycles of therapy or are off study were available for analysis. Baseline characteristics, therapy/safety, response and outcome data were analysed. The primary endpoint is overall response rate (ORR) defined as at least a partial response (PR). As specified in the protocol, we calculated the posterior distribution for ORR using the currently available data and a minimally informative prior distribution (Bayesian updating of the posterior could commence after 12 patients became evaluable) and we report a 95% credible interval (CI) for ORR and also for the clinical benefit rate (CBR) defined as at least a minimal response (MR). We also report an interim summary of PFS. Analyses were performed using R and SAS9.4. Results: Thirty-three patients were enrolled from 2 Australian sites (M:F 24:9), median age: 66 years (41-85). Median number of prior lines of therapy was 1 (1-3). Patients received a median of 6 cycles (1-20). Nine patients (27.3%) received