Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: Updated results of the E1912 trial Journal Article
| Authors: | Shanafelt, T. D.; Wang, X. V.; Hanson, C. A.; Paietta, E. M.; O'Brien, S.; Barrientos, J.; Jelinek, D. F.; Braggio, E.; Leis, J. F.; Zhang, C. C.; Coutre, S. E.; Barr, P. M.; Cashen, A. F.; Mato, A. R.; Singh, A. K.; Mullane, M. P.; Little, R. F.; Erba, H.; Stone, R. M.; Litzow, M.; Tallman, M.; Kay, N. E. |
| Article Title: | Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: Updated results of the E1912 trial |
| 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 aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .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 (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The 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 overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813. © 2022 American Society of Hematology |
| Keywords: | cancer survival; controlled study; treatment outcome; aged; gene mutation; major clinical study; overall survival; genetics; fludarabine; drug tolerability; fatigue; cancer combination chemotherapy; diarrhea; drug efficacy; drug withdrawal; hypertension; side effect; comparative study; rituximab; outcome assessment; follow up; antineoplastic agent; cancer immunotherapy; melanoma; progression free survival; multiple cycle treatment; neutrophil count; anemia; hemolysis; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; cyclophosphamide; arthralgia; febrile neutropenia; rash; cause of death; myelodysplastic syndrome; thorax pain; immunoglobulin heavy chain; immunoglobulin variable region; disease progression; heart failure; long term care; sepsis; piperidines; leukocyte count; second cancer; lung infection; chronic lymphatic leukemia; pericardial effusion; leukocytosis; disease exacerbation; adverse drug reaction; heart ventricle tachycardia; treatment withdrawal; leukemia, lymphocytic, chronic, b-cell; supraventricular tachycardia; lymphocyte count; heart arrest; sinus tachycardia; adenine; international prognostic index; piperidine derivative; clinical outcome; acute myeloid leukemia; heart atrium flutter; non melanoma skin cancer; upper gastrointestinal bleeding; kidney hemorrhage; ibrutinib; time to treatment; heavy chain; humans; human; article; lymphocytic lymphoma; ecog performance status |
| Journal Title: | Blood |
| Volume: | 140 |
| Issue: | 2 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2022-07-14 |
| Start Page: | 112 |
| End Page: | 120 |
| Language: | English |
| DOI: | 10.1182/blood.2021014960 |
| PUBMED: | 35427411 |
| PROVIDER: | scopus |
| PMCID: | PMC9283968 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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