Canadian Cancer Trials Group (Cctg) LY.17: A Randomized Phase Ii Study Evaluating Novel Salvage Therapy Pre‐autologous Stem Cell Transplant (Asct) in Relapsed/Refractory Diffuse Large B Cell Lymphoma (Rr‐dlbcl) ‐ Outcome of Ibrutinib + r‐gdp

Kuruvilla, John; Crump, M.; Villa, Diego; Aslam, Muhammad Imran; Prica, Anca; Scott, David W.; Abdel-Samad, Nizar; Couban, Stephen; Doucet, Stéphane; Dudebout, Jill; Fleury, Isabelle; Fraser, Graeme; Larouche, Jean-François; Shafey, Mona; Skrabek, Pamela; Skamene, Tanya; Winch, Chad; Shepherd, L. E.; Chen, B.E.; Hay, Annette E.

doi:10.1002/hon.2437_76

Cited by 6 publications

(6 citation statements)

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“…In the randomized PHOENIX Phase III study, prolonged neutropenia with more infectious complications in the patient group receiving ibrutinib was observed, as well, in line with our findings [ 27 ]. In a Phase II randomized study, Canadian investigators assessed the combination of ibrutinib with rituximab/gemcitabine/dexamethasone/cisplatin (GDP) [ 31 ]. In that study, 14 DLBCL patients receiving continuous ibrutinib administration at a daily dosage of 560 mg displayed a lower ORR than those treated without ibrutinib, while 5 severe infectious events occurred (with one Grade 5 sepsis and one Grade 5 pneumonia).…”

Section: Discussionmentioning

confidence: 99%

Ibrutinib Associated with Rituximab-Platinum Salt-Based Immunochemotherapy in B-Cell Lymphomas: Results of a Phase 1b-II Study of the LYSA Group

Bonnet

Dupuis

Tilly

et al. 2022

Cancers

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In the post-rituximab era, patients with relapsed/refractory non-Hodgkin B-cell lymphoma (R/R B-NHL) responding to a platinum salt-based salvage regimen can potentially be cured after intensification followed by autologous stem cell transplantation, with the quality of the response to salvage predicting survival. The Bruton tyrosine kinase inhibitor ibrutinib, given as monotherapy or combined with other molecules, has proven effective in numerous B-cell lymphomas. To evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), we conducted a multicenter Phase 1b-II study in transplant-eligible R/R B-NHL patients, with ibrutinib given using a 3-by-3 dose-escalation design. The combination of R-DHAP and ibrutinib (given from Day 1 to Day 21 of each cycle) was associated with dose-limiting hematological, infectious, and renal toxicities, while we were unable to reach a dose to recommend for Phase II. R-DHAOx could only be combined with a daily dosage of 280 mg ibrutinib when administered continuously. R-DHAP combined with intermittent ibrutinib administration (from Day 5 to Day 18) was found to be highly toxic. On the other hand, when this administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to 560 mg but with relevant toxicities. Despite a strong rationale for combining ibrutinib and R-DHAP/R-DHAOx, as both target lymphoma B-cells by different mechanisms, this approach was limited by significant toxicities.

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Section: Discussionmentioning

confidence: 99%

Ibrutinib Associated with Rituximab-Platinum Salt-Based Immunochemotherapy in B-Cell Lymphomas: Results of a Phase 1b-II Study of the LYSA Group

Bonnet

Dupuis

Tilly

et al. 2022

Cancers

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“…Most were nonrandomized phase i/ii trials; the one randomized phase iii trial was an ongoing study by Salles et al 55 comparing pixantrone-rituximab with gemcitabinerituximab in patients with r/r dlbcl. In addition, the search found four randomized phase ii trials: one by Kuruvilla et al 41 comparing ibrutinib plus rituximab and gemcitabine-dexamethasone-cisplatin (r-gdp) with r-gdp alone; one by Sehn et al 60 comparing polatuzumab vedotin plus bendamustine-rituximab (br) with br alone; one by Czuczman et al 38 comparing lenalidomide with investigator's choice; and one by Assouline et al 33 comparing panobinostat with panobinostat-rituximab. In the subsections that follow, we discuss agents and regimens with the most promising evidence for further development in r/r dlbcl.…”

Section: Emerging Treatments For R/r Dlbcl Novel Agentsmentioning

confidence: 99%

“…Serious aes with ibrutinib-br included atrial fibrillation, fatigue, and thrombocytopenia. Another ongoing randomized phase ii multi-arm trial added ibrutinib to r-gdp in 14 patients with r/r dlbcl and compared the combination with r-gdp alone 41 . Preliminary results suggested no advantage with the addition of ibrutinib to r-gdp (orr: 28.6% vs. 50.1% in the control arm), and toxicity was increased because of serious infectious events with the addition of ibrutinib.…”

Section: Ibrutinibmentioning

confidence: 99%

Emerging Therapies for the Treatment of Relapsed or Refractory Diffuse Large B Cell Lymphoma

et al. 2019

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Diffuse large B cell lymphoma (dlbcl) is an aggressive non-Hodgkin lymphoma, accounting for approximately 30% of lymphoma cases in Canada. Although most patients will achieve a cure, up to 40% will experience refractory disease after initial treatment, or relapse after a period of remission. In eligible patients, salvage therapy followed by high-dose therapy and autologous stem-cell transplantation (asct) is the standard of care. However, many patients are transplant-ineligible, and more than half of those undergoing asct will subsequently relapse. For those patients, outcomes are dismal, and novel treatment approaches are a critical unmet need. In this paper, we present available data about emerging treatment approaches in the latter setting and provide a perspective about the potential use of those approaches in Canada

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“…The most important result of this trial is the tolerability of ibrutinib in combination with R-ICE, something not to be taken lightly given the prohibitive dose-limiting toxicities of ibrutinib in combination with R-GDP 6 and rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP). 7 The second important finding is the high rate of response of 90% (complete response [CR] 5 11, partial response 5 7) in a cohort comprising 17 patients with primary refractory disease.…”

Section: Sarit Assouline | Jewish General Hospitalmentioning

confidence: 99%

“…PD-L1 expression is reported in ;10% to 30% of DLBCL cases, possibly explaining the differences in treatment response to PD-1 targeting antibodies between cHL and DLBCL. 6 In addition, PD-L1 expression appears to be higher in activated B-cell DLBCL and is associated with inferior overall survival. 5,6 In both cHL and DLBCL, PD-L1 is also expressed by nonmalignant cells in the tumor microenvironment.…”

Section: Sarit Assouline | Jewish General Hospitalmentioning

confidence: 99%

Improving on R-ICE in relapsed DLBCL

Assouline

2018

Blood

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In this issue of Blood, Sauter et al report the results of a multicenter phase 1 study of rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in combination with ibrutinib in relapsed/refractory diffuse large B-cell lymphoma. 1 This combination was well tolerated and resulted in high response rates.Therapies to improve survival among patients with relapsed and refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are greatly needed, notwithstanding the newly approved chimeric antigen receptor T cell for second relapse of DLBCL. 2

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Canadian Cancer Trials Group (Cctg) LY.17: A Randomized Phase Ii Study Evaluating Novel Salvage Therapy Pre‐autologous Stem Cell Transplant (Asct) in Relapsed/Refractory Diffuse Large B Cell Lymphoma (Rr‐dlbcl) ‐ Outcome of Ibrutinib + r‐gdp

Cited by 6 publications

References 0 publications

Ibrutinib Associated with Rituximab-Platinum Salt-Based Immunochemotherapy in B-Cell Lymphomas: Results of a Phase 1b-II Study of the LYSA Group

Ibrutinib Associated with Rituximab-Platinum Salt-Based Immunochemotherapy in B-Cell Lymphomas: Results of a Phase 1b-II Study of the LYSA Group

Emerging Therapies for the Treatment of Relapsed or Refractory Diffuse Large B Cell Lymphoma

Improving on R-ICE in relapsed DLBCL

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