First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial

. 2022 Sep 01 ; 107 (9) : 2108-2120. [epub] 20220901

Jazyk angličtina Země Itálie Médium electronic

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid35021599

Grantová podpora
21053 Cancer Research UK - United Kingdom

iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or <65 years with coexisting conditions. Patients received oral ibrutinib 420 mg once daily until disease progression or unacceptable toxicity or six cycles of oral chlorambucil, each in combination with six cycles of intravenous obinutuzumab. After a median follow-up of 45 months (range, 0.2-52), median progression-free survival continued to be significantly longer in the ibrutinib plus obinutuzumab arm than in the chlorambucil plus obinutuzumab arm (median not reached versus 22 months; hazard ratio=0.25; 95% confidence interval: 0.16-0.39; P<0.0001). The best overall rate of undetectable minimal residual disease (<0.01% by flow cytometry) remained higher with ibrutinib plus obinutuzumab (38%) than with chlorambucil plus obinutuzumab (25%). With a median treatment duration of 42 months, 13 months longer than the primary analysis, no new safety signals were identified for ibrutinib. As is typical for ibrutinib-based regimens, common grade ≥3 adverse events were most prevalent in the first 6 months of ibrutinib plus obinutuzumab treatment and generally decreased over time, except for hypertension. In this final analysis with up to 52 months of follow-up (median 45 months), ibrutinib plus obinutuzumab showed sustained clinical benefit, in terms of progression- free survival, in first-line treatment of chronic lymphocytic leukemia, including in patients with high-risk features. ClinicalTrials.gov identifier: NCT02264574.

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Burger JA, O'Brien S. Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy. Nat Rev Clin Oncol. 2018;15(8):510-527. PubMed

IMBRUVICA (ibrutinib) [prescribing information]. Sunnyvale, CA: Pharmacyclics LLC, an AbbVie Company; 2020.

Moreno C, Greil R, Demirkan F, et al. . Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. PubMed

Burger JA, Barr PM, Robak T, et al. . Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020;34(3):787-798. PubMed PMC

Shanafelt TD, Wang XV, Kay NE, et al. . Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-443. PubMed PMC

Woyach JA, Ruppert AS, Heerema NA, et al. . Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517-2528. PubMed PMC

Barr PM, Owen C, Robak T, et al. . Up to seven years of follow-up in the RESONATE-2 study of first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. J Clin Oncol. 2021;39(15_suppl):7253.

Byrd JC, Gribben JG, Peterson BL, et al. . Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006;24(3):437-443. PubMed

Munir T, Brown JR, O'Brien S, et al. . Final analysis from RESONATE: up to 6 years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019;94(12):1353-1363. PubMed PMC

Burger JA, Robak T, Demirkan F, et al. . Outcomes of first-line ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and high-risk genomic features with up to 6.5 years follow-up: integrated analysis of two phase 3 studies (RESONATE-2 and iLLUMINATE). Blood. 2020;136(Suppl 1):25-26. PubMed

Hallek M, Cheson BD, Catovsky D, et al. . Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456. PubMed PMC

Al-Sawaf O, Zhang C, Tandon M, et al. . Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(9):1188-1200. PubMed

National Comprehensive Cancer Network. Chronic lymphocytic leukemia/small cell lymphocytic Lymphoma. Version 3.2021. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478

Eichhorst B, Robak T, Montserrat E, et al. . Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(1):23-33. PubMed

Burger JA, Tedeschi A, Barr PM, et al. . Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437. PubMed PMC

Byrd JC, Brown JR, O'Brien S, et al. . Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223. PubMed PMC

Chanan-Khan A, Cramer P, Demirkan F, et al. . Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17(2):200-211. PubMed

Shanafelt TD, Wang V, Kay NE, et al. . Ibrutinib and rituximab provides superior clinical outcome compared to FCR in younger patients with chronic lymphocytic leukemia (CLL): extended follow-up from the E1912 trial. Blood. 2019;134(Suppl 1):33.

Byrd JC, Furman RR, Coutre SE, et al. . Ibrutinib treatment for first-line and relapsed/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib/II PCYC-1102 study. Clin Cancer Res. 2020;26(15):3918-3927. PubMed PMC

Uminski K, Brown K, Bucher O, et al. . Descriptive analysis of dosing and outcomes for patients with ibrutinib-treated relapsed or refractory chronic lymphocytic leukemia in a Canadian centre. Curr Oncol. 2019;26(5):e610-e617. PubMed PMC

Mato AR, Nabhan C, Thompson MC, et al. . Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica. 2018;103(5):874-879. PubMed PMC

Siegel R, DeSantis C, Virgo K, et al. . Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220-241. PubMed

CALQUENCE (acalabrutinib) capsules for oral use [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

Burger JA, Sivina M, Jain N, et al. . Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2019;133(10):1011-1019. PubMed PMC

Tedeschi A, Greil R, Demirkan F, et al. . A cross-trial comparison of single-agent ibrutinib versus chlorambucil-obinutuzumab in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Haematologica. 2020;105(4):e164-e168. PubMed PMC

Sharman JP, Brander DM, Mato AR, et al. . Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial. Lancet Haematol. 2021;8(4):e254-e266. PubMed

Sharman JP, Egyed M, Jurczak W, et al. . Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291. PubMed PMC

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ClinicalTrials.gov
NCT02264574

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