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- Dreyling, Martin, et al.
(författare)
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Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE) : a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
- 2024
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Ingår i: The Lancet. - 0140-6736. ; 403:10441, s. 2293-2306
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.
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| 2. |
- Malm, Tobias, 1979-
(författare)
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Climbing the Trichoptera Tree : Investigations of Branches and Leaves
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Trichoptera (caddisflies) is the largest of the primary aquatic insect orders, currently including more than 13,500 species. With more than 100 species new to science described annually, the known caddisfly diversity is rapidly increasing. In the first four papers of this Thesis, a total of 22 species new to science are described. The first three papers include revisions of the New Caledonian species for the genera Symphitoneuria, Gracilipsodes and Triplectides, with descriptions of 3, 7 and 11 new species, respectively. In these papers I strengthen our image of New Caledonia as a biodiversity hotspot. The fourth paper describes a new genus and species from Madagascar, another biodiversity hotspot. These four papers all deal with species and genera of the family Leptoceridae, which ranks among the three largest families within Trichoptera. The family comprises high species diversity together with a widespread distribution and has been of interest to many trichopterologists. However, the classification used for genera and tribes within the family follows a phylogenetic hypothesis from 1981. In paper V I apply a molecular approach for hypothesising phylogenetic relationships within the family, revealing support for the erection of two tribes to subfamily level and for the synonymisations of 2 pairs of genera. At order level, the progress of illuminating the evolutionary history of Trichoptera is advancing with recent analyses using molecular based data. Previously published phylogenetic hypotheses of the order were to a large degree dependent on ribosomal DNA, a source of molecular data not without its controversies, particularly regarding alignment procedures. Paper VI presents Trichoptera phylogenies based on sequences of protein-coding nuclear and mitochondrial genes. My results correspond well to previously published hypotheses among suborder relationships, but show additional and contrasting resolution within suborders.
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