Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial

Hillmen, Peter; Pitchford, Alexandra; Bloor, Adrian; Broom, Angus; Young, Moya; Kennedy, Ben; Walewska, Renata; Furtado, Michelle; Preston, Gavin; Neilson, Jeffrey R; Pemberton, Nicholas; Sidra, Gamal; Morley, Nicholas; Cwynarski, Kate; Schuh, Anna; Forconi, Francesco; Elmusharaf, Nagah; Paneesha, Shankara; Fox, Christopher P.; Howard, Dena; Hockaday, Anna; Cairns, David A.; Jackson, Sharon; Greatorex, Natasha; Webster, Nichola; Shingles, Jane; Dalal, Sharvari; Patten, Piers; Allsup, David; Rawstron, Andrew; Munir, Talha

doi:10.1016/s1470-2045(23)00144-4

Cited by 36 publications

(35 citation statements)

References 27 publications

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“…The efficacy and tolerability of ibrutinib‐based therapy has been evaluated in five randomized clinical trials, taking into account all patient categories according to age and fitness status 23–27 . In the more elderly and unfit patients ibrutinib alone (Resonate‐2) 23 or in combination with obinutuzumab (Illuminate) 24 was compared to chlorambucil alone or in combination with obinutuzumab respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The aim of this trial was also to evaluate whether the addition of rituximab to single‐agent ibrutinib leads to increased efficacy. In two studies a younger and fit population was randomized to receive FCR or ibrutinib plus rituximab 26,27 …”

Section: Resultsmentioning

confidence: 99%

“…In all the trials ibrutinib alone or in combination with rituximab significantly improved PFS compared to chemotherapy‐based treatment. Results from studies conducted with cBTKi in patients with TN CLL patients are summarized in Table 1 27–33 …”

Section: Resultsmentioning

confidence: 99%

“…In patients with mutated IGHV the PFS benefit of ibrutinib over immuno‐chemotherapy was seen only in the ECOG1912 trial 31 . The favorable PFS exerted by immuno‐chemotherapy in IGHV mutated patients suggests that a prolonged follow‐up of the studies might be needed to see a PFS advantage 27 …”

Section: Resultsmentioning

confidence: 99%

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Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel

Mauro,

Tedeschi,

Varettoni

et al. 2024

Hematological Oncology

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Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first‐line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel

Mauro,

Tedeschi,

Varettoni

et al. 2024

Hematological Oncology

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“…Of note, MRD assessments were only available for a subgroup of the original ITT population; based on available EoT samples in the FCR arm, 90 (63%) of 143 patients had uMRD <10 −4 in PB [5]. More recently, the ECOG1912 study reported 59% and the UK FLAIR study 75% PB uMRD rates their FCR arms, respectively [35, 36]. The study thereby demonstrated that the addition of a CD20 antibody induced deeper remissions than chemotherapy alone.…”

Section: Mrd In the Context Of Chemo- And Chemoimmunotherapymentioning

confidence: 99%

Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia

Al-Sawaf

2023

Acta Haematol

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The level of Minimal residual disease (MRD), often binarized into detectable or undetectable MRD according to certain thresholds, is strongly associated with long-term outcomes after chemo- and chemoimmunotherapy. Driven by our improved understanding of the biology of CLL, the recent decade has shown a shift from chemotherapy-based regimens to regimens based on targeted agents that exploit distinct biological vulnerabilities of CLL. These targeted agents can be broadly classified into inhibitors of Bruton Tyrosine Kinase (BTK) and BCL2 as well as CD20-directed antibodies. Depending on which agent and which combination of agents is used, the levels or status of MRD can have varying clinical relevance. This has implications on the prognosis after therapy as well as on possible strategies to guide treatment duration and intensity. This review summarizes the main discoveries related to MRD in the context of targeted therapies. Furthermore, it provides an overview on current hurdles and caveats related to the implementation of MRD in regular clinical care and summarizes open research questions that need to be addressed with future clinical studies.

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Frontline Therapy of CLL—Changing Treatment Paradigms

Coombs

2024

Curr Hematol Malig Rep

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Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial

Cited by 36 publications

References 27 publications

Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel

Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel

Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia

Frontline Therapy of CLL—Changing Treatment Paradigms

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