2018 ASCO Annual Meeting!
Session: Pediatric Oncology I
Type: Oral Abstract Session
Time: Saturday June 2, 3:00 PM to 6:00 PM
COG AALL0434: A randomized trial testing nelarabine in newly diagnosed t-cell malignancy.
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 10500)
Author(s): Kimberly P. Dunsmore, Stuart Winter, Meenakshi Devidas, Brent L. Wood, Natia Esiashvili, Nancy Eisenberg, Nikki Briegel, Robert J. Hayashi, Julie M Gastier-Foster, Andrew J Carroll, Nyla A. Heerema, Barbara Asselin, Karen R. Rabin, Patrick Zweidler-McKay, Elizabeth A. Raetz, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Stephen Hunger; Carilion Children's, Roanoke, VA; Children's Minnesota, Minneapolis, MN; University of Florida, Gainesville, FL; Department of Laboratory Medicine, University of Washington, Seattle, WA; Department of Radiation Oncology and Winship Cancer Institute of Emory University, Atlanta, GA; University of New Mexico, Albuquerque, NM; Princess Margaret Hospital for Children, Subiaco, Australia; Washington University School of Medicine in St. Louis, St. Louis, MO; Nationwide Children's Hospital, Columbus, OH; Children's Hospital of Alabama, Birmingham, AL; The Ohio State University Comprehensive Cancer Center, Columbus, OH; Univ of Rochester, Rochester, NY; Texas Children's Cancer Center, Houston, TX; ImmunoGen, Waltham, MA, US; University of Utah, Salt Lake City, UT; University of California, San Francisco, San Francisco, CA; The University of Texas Southwestern Medical Center, Dallas, TX; NYU Langone Medical Center, New York, NY; Children's Hospital of Philadelphia, Philadelphia, PA
Background: Nelarabine (Nel) is a T-cell specific agent, FDA approved for patients who have failed at least two chemotherapy regimens. COG AALL0434 evaluated its safety and efficacy when incorporated into COG augmented BFM (ABFM) chemotherapy in newly diagnosed T-ALL and T-LL patients. Methods: AALL0434 enrolled 1,895 patients (2007-2014) and included a 2 x 2 pseudo-factorial randomization using the ABFM regimen. Patients were randomized to receive escalating dose methotrexate without leucovorin rescue + pegaspargase (CMTX) or High Dose MTX (HDMTX) + leucovorin rescue. Intermediate and high-risk patients with T-ALL and T-LL were randomized to receive or not receive six 5-day courses of (Nel) 650 mg/m2/day. The intermediate and high risk T-ALL patients received prophylactic (1200 cGy) or therapeutic (1800 cGy for CNS3) cranial irradiation. T-ALL patients with induction failure were non-randomly assigned to HDMTX+Nel. Results: For all randomized T-ALL patients, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 84.3 +/- 1.1% and 90.2 +/- 0.9%. The 4-year DFS rate for T-ALL patients randomized to Nel (N = 323) vs no Nel (N = 336) was 88.9 +/- 2.2% vs 83.3 +/- 2.5%, (p = 0.0332). Among T-ALL patients randomized to CMTX the 4-year DFS for Nel (N = 147) vs no Nel (N = 151) was 92.2 +/- 2.8% vs 89.8 +/- 3.0%, p = 0.3825. For those randomized to HDMTX, 4-year DFS was 86.2 +/- 3.2% with Nel (N = 176) vs 78.0 +/- 3.7% without Nel (N = 185), p = 0.024. Differences between DFS in a 4-arm comparison were highly significant (P = 0.002), with no significant interactions between MTX and nelarabine randomizations (p = 0.41). T-ALL induction failure patients (N = 43) assigned to HDMTX/Nel had a 4-year DFS of 54.8 +/- 8.9%. Nelarabine did not show an advantage for high risk T-LL patients, with 4-year DFS 85.0 +/- 5.6% vs 89.0 +/- 4.7% for Nel (N = 60) vs no Nel (N = 58), p = 0.2788. Overall toxicity and neurotoxicity were acceptable and not significantly different between all four arms. Conclusions: COG AALL0434 is the largest trial ever conducted for newly diagnosed T-ALL and T-LL, and showed outstanding overall outcomes. Nelarabine improves DFS for children and young adults with T-ALL and should become a new standard of care for this population. Clinical trial information: NCT00408005