Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: Updated results of the E1912 trial

Authors

Tait D. Shanafelt, Stanford University School of Medicine, Stanford, California, United States.
Xin Victoria Wang, Dana Farber Cancer Institute - ECOG-ACRIN Biostatistics Center, Boston, Massachusetts, United States.
Curtis A. Hanson, Mayo Clinic, Rochester, Minnesota, United States.
Elisabeth M. Paietta, Montefiore Medical Center, Bronx, New York, United States.
Susan O'Brien, University of California Irvine, Orange, California, United States.
Jacqueline C. Barrientos, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York, United States.Follow
Diane F. Jelinek, Mayo Clinic, Scottsdale, Arizona, United States.
Esteban Braggio, Mayo Clinic Arizona, Scottsdale, Arizona, United States.Follow
Jose F. Leis, Mayo Clinic, Phoenix, Arizona, United States.
Cong Christine Zhang, Kaiser Permanente NCORP, Fresno, California, United States.
Steven E. Coutre, Stanford University School of Medicine, Stanford, California, United States.Follow
Paul M. Barr, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, United States.Follow
Amanda F. Cashen, Washington University School of Medicine, St Louis, Missouri, United States.Follow
Anthony R. Mato, Memorial Sloan Kettering Cancer Center, New York, New York, United States.
Avina K. Singh, Minnesota Oncology, Burnsville, Minnesota, United States.
Michael P. Mullane, Advocate Aurora HealthFollow
Richard F. Little, National Cancer Institute, Bethesda, Maryland, United States.
Harry P. Erba, Duke University, Durham, North Carolina, United States.
Richard M. Stone, Dana-Farber Cancer Institute, Boston, Massachusetts, United States.
Mark R. Litzow, Mayo Clinic, Rochester, Minnesota, United States.
Martin S. Tallman, Memorial Sloan-Kettering Cancer Center, New York, New York, United States.
Neil E. Kay, Mayo Clinic, Rochester, Minnesota, United States.

Affiliations

Aurora Cancer Care

Abstract

Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients with CLL age (2:1 ratio) to receive ibrutinib and rituximab (IR) or six cycles of FCR. With a median follow-up of 5.8 years, median PFS is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in both IGHV mutated (HR: 0.27; P < 0.001) and IGHV unmutated patients (HR: 0.27; P < 0.001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events/complication, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. Median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in OS was observed for patients on the IR arm (HR=0.47; p=0.018). In conclusion, Ibrutinib-rituximab therapy offers superior PFS relative to FCR in both IGHV mutated and unmutated CLL patients as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. Clinical trial at NCT02048813.

Document Type

Article

PubMed ID

35427411


 

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