Efficacy of nivolumab in a patient with systemic refractory ALK+ anaplastic large cell lymphoma

Rigaud, Charlotte; Abbou, Samuel; Minard‐Colin, Véronique; Geoerger, Birgit; Scoazec, Jean Yves; Vassal, Gilles; Jaff, Nabaz; Heuberger, Laurence; Valteau‐Couanet, Dominique; Brugières, Laurence

doi:10.1002/pbc.26902

Cited by 47 publications

(38 citation statements)

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“…Although clinical experience with checkpoint inhibitors in anaplastic large cell lymphoma is limited to individual case reports [46,47] there is a strong biological rationale for their use based on the observed expression of cellsurface PD-L1 in anaplastic lymphoma kinase translocated cell lines and tumour samples [48]. Therefore, nivolumab is being evaluated in a phase II trial in paediatric and adult relapsing/refractory anaplastic lymphoma kinaseetranslocated anaplastic large cell lymphoma [49].…”

Section: The Way Forward For Checkpoint Inhibitors In Lymphomasdanaplmentioning

confidence: 99%

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

Pearson¹,

Rössig

Lesa

et al. 2020

European Journal of Cancer

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Section: The Way Forward For Checkpoint Inhibitors In Lymphomasdanaplmentioning

confidence: 99%

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

Pearson¹,

Rössig

Lesa

et al. 2020

European Journal of Cancer

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“…These new findings suggest the potential use of anti-PD-L1 therapy for these cancers. Recently, a refractory ALK-positive ALCL patient has demonstrated prolonged responses to the PD-1 inhibitor, nivolumab, with dramatic reduction of physical pain and tumor size [54]. On the other hand, isolated reports noted that some NSCLC patients with ALK rearrangements or EGFR mutations had low response rates to PD-1/PD-L1 inhibitors, possibly due to low PD-L1 expression and low levels of infiltrating CD8+T lymphocytes in tumors [55].…”

Section: Immune Checkpoint Inhibitors In Alk-positive Cancersmentioning

confidence: 99%

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Wang

Lui

2020

Cancers

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Anaplastic lymphoma kinase (ALK) is mostly known for its oncogenic role in several human cancers. Recent evidences clearly indicate new roles of ALK and its genetic aberrations (e.g. gene rearrangements and mutations) in immune evasion, innate and cell-mediated immunity. New ALK-related immunotherapy approaches are demonstrating both preclinical and clinical promises. Here, we provide a timely review on the most updated laboratory and patient-related findings on ALK and immunity, which would grant us important insights for the development of novel ALK immunotherapies for ALK-altered cancers.

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“…11 In anaplastic large cell lymphoma (ALCL), PD-1 blockade has been reported effective for patients with both ALK-negative and ALK-positive ALCL. [29][30][31] There is an accumulating body of evidence showing the impact of the expression of PD-1 axis members in predicting the response to anti-PD-1 directed therapies. [32][33][34][35][36][37] Preliminary data from clinical trials in solid tumors and Hodgkin lymphoma suggested PD-L1 expression to be crucial for the response to PD-1/PD-L1 blockade.…”

Section: Introductionmentioning

confidence: 99%

Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation

et al. 2020

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Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4 + T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4 + T cells from SS patients and to CD4 + cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor.

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Efficacy of nivolumab in a patient with systemic refractory ALK+ anaplastic large cell lymphoma

Cited by 47 publications

References 11 publications

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation

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