Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trněný, Marek; Offner, Fritz; Caballero, Dolores; João, Cristina; Witzens-Harig, Mathias; Heß, Georg; Bence‐Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D.; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

doi:10.1016/s0140-6736(15)00667-4

Cited by 419 publications

(366 citation statements)

References 28 publications

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“…In randomized trials, ibrutinib is effective as first-line treatment of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) (compared with chlorambucil), 1 for relapsed/refractory CLL/SLL (compared with ofatumumab or combined with bendamustine/rituximab), 2,3 or for relapsed/refractory mantle cell lymphoma (compared with temsiroliums), 4 with promising results in the treatment of Waldenström macroglobulinemia. 5 It is anticipated that ibrutinib will become an important part of the therapeutic armamentarium for these conditions.…”

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confidence: 99%

The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis

Leong

Caron

Hillis

et al. 2016

Blood

206

117

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Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase in the B-cell receptor signaling pathway. In randomized trials, ibrutinib is effective as first-line treatment of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) (compared with chlorambucil), 1 for relapsed/refractory CLL/SLL (compared with ofatumumab or combined with bendamustine/rituximab), 2,3 or for relapsed/refractory mantle cell lymphoma (compared with temsiroliums), 4 with promising results in the treatment of Waldenström macroglobulinemia. 5 It is anticipated that ibrutinib will become an important part of the therapeutic armamentarium for these conditions. Randomized trials suggest that ibrutinib may increase the risk of atrial fibrillation (AF) as compared with chlorambucil 1 or ofatumumab. 2 In the general population, AF is strongly associated with heart failure and arterial thromboembolism, which result in substantial morbidity and mortality. There is uncertainty over the magnitude of the increase in AF risk attributable to ibrutinib because the absolute numbers of incident AF cases are small in individual studies.We undertook a systematic review and meta-analysis to (1) estimate the magnitude of the increase in AF risk among ibrutinib recipients, as compared with alternative therapies and (2) quantify the frequency of AF reported among ibrutinib recipients. We searched MEDLINE and EMBASE, and proceedings from the American Society of Hematology, the European Haematology Association, and the American Society of Clinical Oncology for articles describing AF rates in recipients of ibrutinib. The following search terms were used: ibrutinib; imbruvica; or PCI-32765. Animal studies, case reports, case series (ie, that reported on consecutive AF cases), cross-sectional studies, editorials, phase I/dose-finding studies, and conference abstracts more than 12 months old were excluded.Two independent reviewers screened the articles' titles and abstracts for eligibility. Cases of disagreement were resolved by a third reviewer. Papers identified after title and abstract screening were obtained in full. When data from the same cohort of participants were presented in different papers, only the manuscript with the larger sample size was included in the meta-analysis. The following data were extracted from eligible full text manuscripts: design, disease, sample size, treatments, participant age and sex, follow-up duration, AF rates, and where reported, AF ascertainment strategies, past history of cardiovascular disease, AF, or hypertension.Statistical analysis was performed using STATA 14 (StataCorp, College Station, TX). To evaluate the increase in the risk of incident AF, the primary meta-analytic approach was a fixed effects model using the Mantel-Haenszel method. A sensitivity analysis was performed using a DerSimonian and Laird random effects model. Heterogeneity of studies was evaluated by Cochran's Q and the I 2 statistic. Pooled AF rates were estimated as follows: we multiplied the median follow-up duration by the sample siz...

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mentioning

confidence: 99%

The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis

Leong

Caron

Hillis

et al. 2016

Blood

206

117

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“…Subgroup analyses of a single‐arm phase II trial of ibrutinib in 111 patients with relapsed/refractory MCL found similar ORRs, irrespective of multiple baseline factors, including tumour bulk (≥5 and ≥10 cm cut‐offs), ≥2 prior treatment regimens and refractory disease (less than partial response to last prior therapy) (Wang et al , 2015). More recently, an open‐label phase III study showed that ibrutinib was superior to temsirolimus with regard to improvements in PFS overall and when broken down by subgroups (Dreyling et al , 2016). …”

Section: Discussionmentioning

confidence: 99%

Prospective subgroup analyses of the randomized MCL‐002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma

et al. 2017

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SummaryIn the mantle cell lymphoma (MCL)‐002 study, lenalidomide demonstrated significantly improved median progression‐free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long‐term follow‐up data and results of preplanned subgroup exploratory analyses from MCL‐002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL‐002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1–21; 28‐day cycles) or single‐agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent‐to‐treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single‐agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history.

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“…Despite the recent approval of novel therapies, patients with rr mcl generally respond poorly to treatment, with the median os typically being only 1-2 years 11 . Median progression-free survival (pfs) ranges from 3.9 months to 14.6 months, and overall response rates (orrs) range from 22% to 72% depending on the type of treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Median progression-free survival (pfs) ranges from 3.9 months to 14.6 months, and overall response rates (orrs) range from 22% to 72% depending on the type of treatment. Although no current standard of care has been established in the rr setting, ibrutinib shows the most promising single-agent efficacy of the currently approved agents, being associated with a median pfs of 13.6-14.6 months and with orrs ranging from 54% to 72% [11][12][13] . In comparison, the reported median pfs was 9.2 months for bortezomib, 3.9-8.7 months for lenalidomide, and 4.8-6.2 months for temsirolimus.…”

Section: Introductionmentioning

confidence: 99%

“…The oral first-generation once-daily Bruton tyrosine kinase (btk) inhibitor ibrutinib binds covalently to a cysteine residue (Cys481) in the active site of the atp-binding domain of btk, inhibiting B-cell receptor signalling, thereby reducing cell growth, proliferation, survival, adhesion, and migration 11 . With the success of ibrutinib in hematologic malignancies, novel btk inhibitors designed to improve on its safety and efficacy are being developed.…”

Section: Introductionmentioning

confidence: 99%

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Updates from the 2017 American Society of Hematology Annual Meeting: Practice-Changing Studies in Relapsed and Refractory Mantle Cell Lymphoma

Kuruvilla

Christofides

2018

Current Oncology

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The 2017 annual meeting of the American Society of Hematology took place 9-12 December in Atlanta, Georgia. At the meeting, results from key studies in the treatment of relapsed and refractory mantle cell lymphoma were presented. Of those studies, oral presentations focused on the efficacy and safety of therapy with Bruton tyrosine kinase (btk) inhibitors. One study presented pooled data from three trials using ibrutinib, with a median follow-up of 3.5 years. A second phase ii study presented data on the efficacy and safety of acalabrutinib, a highly selective btk inhibitor with minimal off-target activity. The final study presented early phase ib data on the efficacy and safety of zanubrutinib, a novel, highly selective btk inhibitor, in patients with non-Hodgkin lymphoma. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice.

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Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study

Cited by 419 publications

References 28 publications

The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis

The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis

Prospective subgroup analyses of the randomized MCL‐002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma

Updates from the 2017 American Society of Hematology Annual Meeting: Practice-Changing Studies in Relapsed and Refractory Mantle Cell Lymphoma

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