Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Efstathios Kastritis , Angela Dispenzieri , Ashutosh D. Wechalekar , Stefan O. Schönland , Kihyun Kim , Vaishali Sanchorawala , Heather Jolie Landau , Fiona Kwok , Kenshi Suzuki , Ray Comenzo , Giovanni Palladini , Deborah Berg , Guohui Liu , Arun Kumar , Douglas V. Faller , Giampaolo Merlini
Background: The PI bortezomib is commonly used in first-line therapy of AL, but new therapies are needed that are tolerable in the context of multi-organ dysfunction and that, in RRAL, offer improved outcomes following prior bortezomib. Ixazomib is an oral PI, and in TOURMALINE-AL1, the first phase 3 trial conducted in RRAL, while the first primary endpoint of hematologic overall response rate (ORR) was not met, all clinically relevant time-to-event endpoint data favored Ixa-Dex vs PC (Dispenzieri et al, ASH 2019). Methods: RRAL pts with 1–2 prior therapies were randomized (1:1) to Ixa-Dex (n = 85) or PC (n = 83; Dex plus lenalidomide [n = 47], melphalan [n = 24], cyclophosphamide [n = 10], or thalidomide [n = 2]), stratified by cardiac stage, relapsed vs refractory disease, and prior PI exposure. The primary endpoints were hematologic ORR and 2-yr rate of vital organ deterioration or death. We report subgroup analyses of ORR and outcomes by prior PI exposure. Results: Of the 168 pts enrolled, 90 were PI-naïve and 78 PI-exposed (46 and 39 in the Ixa-Dex arm; 44 and 39 in the PC arm) per stratification; 28 and 27 pts in the Ixa-Dex and PC arms had received bortezomib in their last prior line. Hematologic ORR was 63% vs 50% for Ixa-Dex vs PC (odds ratio [OR] 1.71; 95% confidence interval [CI] 0.74–3.96) in PI-naïve pts, and 41% vs 51% (OR 0.66; 95% CI 0.27–1.62) in PI-exposed pts. For time-to-event outcomes (Table), hazard ratios (HRs) were 0.46–0.85 in favor of Ixa-Dex vs PC in both PI-naïve and PI-exposed pts. Conclusions: Hematologic ORR was higher with Ixa-Dex vs PC in PI-naïve pts but lower in PI-exposed pts (although not statistically significant), and long-term clinically relevant outcomes favored Ixa-Dex in both groups. Based on HRs, the magnitude of benefit appeared similar or greater in PI-naïve vs PI-exposed pts. Clinical trial information: NCT01659658.
PI-naïve | PI-exposed | |||||
---|---|---|---|---|---|---|
Median, mos | Ixa-Dex | PC | HR (95% CI) | Ixa-Dex | PC | HR (95% CI) |
Time to vital organ deterioration or death | 44.9 | 28.0 | 0.53 (0.24–1.18); p = 0.112 | 27.0 | 26.1 | 0.52 (0.27–1.01); p = 0.050 |
Composite progression-free survival | 30.4 | 9.8 | 0.56 (0.31–1.02); p = 0.054 | 7.0 | 5.5 | 0.77 (0.46–1.28); p = 0.309 |
Time to treatment failure | 16.2 | 5.3 | 0.46 (0.27–0.79); p = 0.004 | 7.0 | 5.2 | 0.76 (0.47–1.23); p = 0.262 |
Time to subsequent therapy | 61.4 | 16.3 | 0.57 (0.29–1.09); p = 0.084 | 15.7 | 12.1 | 0.66 (0.37–1.18); p = 0.156 |
Overall survival | Not reached | 71.1 | 0.81 (0.37–1.80); p = 0.610 | 40.9 | 32.4 | 0.85 (0.46–1.60); p = 0.616 |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Andrew Spencer
2022 ASCO Annual Meeting
First Author: Paul G. Richardson
2022 ASCO Annual Meeting
First Author: Laurie Helen Sehn
2023 ASCO Annual Meeting
First Author: Loretta J. Nastoupil