Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSé-crizotinib trial

Brugières, Laurence; Cozic, Nathalie; Houot, Roch; Rigaud, Charlotte; Sibon, David; Arfi-Rouche, Julia; Bories, Pierre; Delmer, Alain; Ducassou, Stéphane; Garnier, Nathalie; Lamant, Laurence; Leruste, Amaury; Millot, Frédéric; Moalla, Salma; Morschhauser, Franck; Nolla, M. Clavel-Sáinz; Pagnier, Anne; Réguerre, Yves; Renaud, Loïc; Schmitt, Anna; Simonin, Mathieu; Verschuur, Arnauld; Labouret, Natalie Hoog; Oukhatar, Céline Mahier Ait; Vassal, Gilles

doi:10.1016/j.ejca.2023.112984

Cited by 10 publications

(2 citation statements)

References 28 publications

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“…The overall response rate at 8 weeks was 67% (95% CI: 47–82%), with 80% (95% CI: 44−97%) in children/adolescents and 57% (95% CI: 29−82%) in adults. The PFS and OS rates at 3 years were 40% (95% CI, 23–59%) and 63% (95% CI, 43–79%), respectively ( 10 ). In an open-label phase II trial, crizotinib was administered to 26 pediatric patients with relapsed or refractory ALK+ ALCL, achieving an objective response rate of 90% ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL

Liu,

Wu,

Ming

et al. 2024

Front. Immunol.

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BackgroundAnaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare, mature T-cell non-Hodgkin lymphoma. The prognosis of patients with relapsed or refractory ALCL following first-line chemotherapy is extremely poor. NCCN guidelines recommend intensified chemotherapy with or without ASCT consolidation for r/r ALCL, however, this is not an effective treatment for all ALK+ALCL.Case reportHerein, we report a patient with relapsed/refractory ALK+ ALCL who received crizotinib and brentuximab vedotin as bridging therapy, followed by autologous stem cell transplantation and sequential anti-CD30 CAR T cell therapy.ConclusionThe patient achieved complete remission and long-term disease-free survival of months and continues to be followed up. The combination therapy model in this case may provide guidance for the management of relapsed/refractory ALK+ ALCL, and further prospective trials are needed to confirm its effectiveness.

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Section: Discussionmentioning

confidence: 99%

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL

Liu,

Wu,

Ming

et al. 2024

Front. Immunol.

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“…These oncogenic properties include cell immortalization and protection from cell death, enabled at least in part by activation of stem cell-related genes ( 40 ), induction of multi-faceted inhibition of anti-tumor immune response ( 35 ), epigenetic silencing of TCR- and cytokine-signaling genes acting in the context of NPM1::ALK as tumor suppressors ( 35 ), protection from hypoxia ( 35 ), and mobilization of the metabolic NAD synthesis salvage pathway to sustain enzymatic activity of the oncogenic ALK ( 41 ). Given the above diverse pro-oncogenic effects of NPM1::ALK, it is not surprising that targeting ALK clinically induces complete, long-lasting remissions in response to crizotinib, the first generation ALK inhibitor ( 42 , 43 ). However, resistance to ALK-inhibition monotherapy has emerged ( 44 ), even to the second- and third-generation, highly potent ALK inhibitors, providing rationale for a combination therapy to prevent development of the resistance.…”

Section: Malignant Transformation Of T and B Lymphocytes Driven By Ch...mentioning

confidence: 99%

Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications

Wasik,

Kim,

Nejati

2024

Front. Oncol.

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While normal B- and T-lymphocytes require antigenic ligands to become activated via their B- and T-cell receptors (BCR and TCR, respectively), B- and T-cell lymphomas show the broad spectrum of cell activation mechanisms regarding their dependence on BCR or TCR signaling, including loss of such dependence. These mechanisms are generally better understood and characterized for B-cell than for T-cell lymphomas. While some lymphomas, particularly the indolent, low-grade ones remain antigen-driven, other retain dependence on activation of their antigen receptors seemingly in an antigen-independent manner with activating mutations of the receptors playing a role. A large group of lymphomas, however, displays complete antigen receptor independence, which can develop gradually, in a stepwise manner or abruptly, through involvement of powerful oncogenes. Whereas some of the lymphomas undergo activating mutations of genes encoding proteins involved in signaling cascades downstream of the antigen-receptors, others employ activation mechanisms capable of substituting for these BCR- or TCR-dependent signaling pathways, including reliance on signaling pathways physiologically activated by cytokines. Finally, lymphomas can develop cell-lineage infidelity and in the extreme cases drastically rewire their cell activation mechanisms and engage receptors and signaling pathways physiologically active in hematopoietic stem cells or non-lymphoid cells. Such profound reprograming may involve partial cell dedifferentiation or transdifferentiation towards histocytes, dendritic, or mesodermal cells with various degree of cell maturation along these lineages. In this review, we elaborate on these diverse pathogenic mechanisms underlying cell plasticity and signaling reprogramming as well as discuss the related diagnostic and therapeutic implications and challenges.

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Outcome of childhood ALK‐positive anaplastic large cell lymphoma relapses: Real‐life experience of the French Society of Pediatric Oncology (SFCE) cohort of 75 French children

Pereira,

Barthoulot,

Aladjidi

et al. 2024

Pediatric Blood & Cancer

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ObjectiveTo describe treatments and outcomes of French children treated for relapsed/refractory anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma (ALK+ ALCL).MethodsWe conducted the analysis of a series of 75 French children treated for a first relapsed/refractory ALK+ ALCL between 1999 and 2017.ResultsThe median time to first relapse was 8.1 months from initial diagnosis (2.9 after end of treatment), with 12 relapses during frontline treatment or within 1 month of the end of treatment. Treatment of the first relapse varied according to the period of time and risk factors: 48 received multiagent chemotherapy, including 21 and 19 consolidated with allogeneic stem cell transplantation (SCT) and autologous‐SCT, respectively. Twenty‐one patients received weekly vinblastine, and six received ALK inhibitors (ALKi). Overall, 64/75 patients reached a second complete remission (CR2). Eight out of 11 patients who did not reach CR2 died and the other three were rescued with ALKi, vinblastine, and nivolumab. With a median follow‐up of 8.2 years, 60 patients are alive, 43 in CR2, 15 in CR3, two in CR4; and 15 patients died, six from toxicity and nine from disease progression. The 5‐year event‐free survival and overall survival after first relapse were 51.7% (95% confidence interval [CI]: 39.6%–62.6%) and 80.7% (95% CI: 69.6%–88.1%), respectively. Time to relapse greater than 12 months from initial diagnosis was proven to be a prognostic factor in relapsed/refractory ALK+ ALCL.ConclusionIn relapsed ALK+ ALCL, high survival rate can be reached with various therapeutic strategies. The main challenge remains to prevent subsequent relapses, and to lower long‐term morbidity.

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Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSé-crizotinib trial

Cited by 10 publications

References 28 publications

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL

Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications

Outcome of childhood ALK‐positive anaplastic large cell lymphoma relapses: Real‐life experience of the French Society of Pediatric Oncology (SFCE) cohort of 75 French children

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