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Idelalisib in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: First Results from the Nordic Lymphoma Group NLG-LBC-07 (ILIAD) Phase II Trial
Introduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) who are ineligible for intensive chemotherapy and autologous stem cell transplantation have limited therapeutic options and poor prognosis, and there is an unmet need for new therapeutic alternatives in this si...
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Published in: | Blood 2020-11, Vol.136 (Supplement 1), p.33-33 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Introduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) who are ineligible for intensive chemotherapy and autologous stem cell transplantation have limited therapeutic options and poor prognosis, and there is an unmet need for new therapeutic alternatives in this situation. Based on gene expression profiling, DLBCL can be divided into the germinal centre B-cell (GCB) and the activated B-cell (ABC) subtype. These subtypes are dependent on different oncogenic pathways and may differ in responsiveness to targeted therapies. Idelalisib is a small-molecule inhibitor of PI3Kδ, currently approved for treatment of follicular lymphoma and CLL. Based on the high response rate of idelalisib in heavily pretreated patients with indolent B-cell lymphomas, among whom many may have undetected transformed disease, we hypothesized that idelalisib may also be active in r/r DLBCL, particularly in the GCB subtype, due to frequent PTEN loss and unregulated activation of PI3K signaling in this subtype. Here, we evaluated the efficacy and safety of idelalisib as a single agent therapy in patients with r/r DLBCL in a multi-centre phase II non-randomized trial. To our knowledge, this is the first prospective study on the use of single agent idelalisib in patients with DLBCL.
Methods: Eligibility criteria were: Patients with DLBCL, including transformed low-grade lymphoma, with r/r disease after at least one rituximab-containing chemotherapy regimen, WHO PS 0-3, and not candidate for autologous stem cell transplantation. The primary endpoint was maximal overall response rate (ORR) measured with CT and PET/CT for the GCB-DLBCL. Idelalisib 150 mg x 2 p o was given until progression or unacceptable toxicity.
Results: In the period 2017-2020, 36 patients were included from six centers in Sweden and Denmark, 18 patients showed a GCB and 16 patients an ABC subtype, two patients could not be classified for subtype. The study was terminated prematurely due to futility in reaching the primary endpoint. The median age was 74 years. Patients had received a median of three previous regimens. In total, 34/36 patients have discontinued treatment (n=24 due to PD, n=7 due to an adverse advent (AE), n=2 due to death, n=1 due to other cause). Median duration of treatment was 8 weeks (range 2-92), see the swimmers plot. Treatment emergent-AEs of grade 3 or higher included elevated liver transaminases (n=6), hematological toxicity (n=4), colitis (n=2), CMV reactivation |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2020-133359 |