Posttransplant cyclophosphamide after allogeneic hematopoietic cell transplantation mitigates the immune activation induced by previous nivolumab therapy

Nieto, Juan C.; Roldán, Elisa; Jiménez, Isabel; Fox, Laura; Carabia, Júlia; Ortí, Guillermo; Puigdefàbregas, Lluís; Gallur, Laura; Iacoboni, Gloria; Raheja, Priyanka; Pérez, A.; Bobillo, Sabela; Salamero, Olga; Palacio, Carlos; Valcárcel, David; Crespo, Marta; Bosch, Francesc; Barba, Pere

doi:10.1038/s41375-020-0851-8

Cited by 22 publications

(16 citation statements)

References 15 publications

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“…However, patients receiving PT-Cy showed a similar risk of aGvHD and T-cell profile irrespective of the previous Nivo exposure. This T-cell activation status can be mitigated with the use of PT-Cy, thus reducing the risk of aGvHD [65].…”

Section: Why Does Pt-cy Prophylaxis Improve Outcomes?mentioning

confidence: 99%

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

et al. 2021

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Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody–drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.

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Section: Why Does Pt-cy Prophylaxis Improve Outcomes?mentioning

confidence: 99%

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

et al. 2021

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“…71 Data from two small studies of anti-PD-1 suggest that prophylactic cyclophosphamide post-transplant may improve GVHD-related outcomes in this population. 72,73 In a systematic review of 19 studies, receiving ICI [ipilimumab (n ¼ 85), nivolumab (n ¼ 76), pembrolizumab (n ¼ 16)] after allo-HSCT had high efficacy (ORR: 54%) and risk of GVHD (14% acute, 11% chronic), with a GVHD mortality risk of 7%. 70 Incidentally, historical rates of GVHD in patients without any ICI exposure (before or after) were found to be 30%-50% for acute 70,74 and up to 28% for de novo chronic GVHD.…”

Section: Immunodeficiency Including Transplant Recipientsmentioning

confidence: 99%

Immunotherapy use outside clinical trial populations: never say never?

et al. 2021

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Background: Based on favourable outcomes in clinical trials, immune checkpoint inhibitors (ICIs), most notably programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, are now widely used across multiple cancer types. However, due to their strict inclusion and exclusion criteria, clinical studies often do not address challenges presented by non-trial populations. Design: This review summarises available data on the efficacy and safety of ICIs in trial-ineligible patients, including those with autoimmune disease, chronic viral infections, organ transplants, organ dysfunction, poor performance status, and brain metastases, as well as the elderly, children, and those who are pregnant. In addition, we review data concerning other real-world challenges with ICIs, including timing of therapy switch, relationships to radiotherapy or surgery, re-treatment after an immune-related toxicity, vaccinations in patients on ICIs, and current experience around ICI and coronavirus disease-19. Where possible, we provide recommendations to aid the oftendifficult decision-making process in those settings. Conclusions: Data suggest that ICIs are often active and have an acceptable safety profile in the populations described above, with the exception of PD-1 inhibitors in solid organ transplant recipients. Decisions about whether to treat with ICIs should be personalised and require multidisciplinary input and careful counselling of patients with respect to potential risks and benefits. Clinical judgements need to be carefully weighed, considering factors such as underlying cancer type, feasibility of alternative treatment options, or activity in trial-eligible patients.

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“…Nieto et al investigated clinical samples of patients treated with nivolumab before HSCT and demonstrated that nivolumab was detectable in the plasma for up to 56 days after HSCT was performed, and this residual nivolumab could bind to and block PD-1 expressed on donor effector T cells during this period. They also showed that pretransplant nivolumab resulted in a high frequency of IFN-γ-producing effector T cells, which might contribute to severe GVHD after transplantation ( 85 ).…”

Section: Effects Of Immune-checkpoint Inhibitors On Treg Homeostasismentioning

confidence: 99%

Harnessing Treg Homeostasis to Optimize Posttransplant Immunity: Current Concepts and Future Perspectives

Ikegawa

Matsuoka

2021

Front. Immunol.

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CD4+CD25+Foxp3+ regulatory T cells (Tregs) are functionally distinct subsets of mature T cells with broad suppressive activity and have been shown to play an important role in the establishment of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs exhibit an activated phenotype from the stage of emigration from the thymus and maintain continuous proliferation in the periphery. The distinctive feature in homeostasis enables Tregs to respond sensitively to small environmental changes and exert necessary and sufficient immune suppression; however, on the other hand, it also predisposes Tregs to be susceptible to apoptosis in the inflammatory condition post-transplant. Our studies have attempted to define the intrinsic and extrinsic factors affecting Treg homeostasis from the acute to chronic phases after allogeneic HSCT. We have found that altered cytokine environment in the prolonged post-HSCT lymphopenia or peri-transplant use of immune checkpoint inhibitors could hamper Treg reconstitution, leading to refractory graft-versus-host disease. Using murine models and clinical trials, we have also demonstrated that proper intervention with low-dose interleukin-2 or post-transplant cyclophosphamide could restore Treg homeostasis and further amplify the suppressive function after HSCT. The purpose of this review is to reconsider the distinctive characteristics of post-transplant Treg homeostasis and discuss how to harness Treg homeostasis to optimize posttransplant immunity for developing a safe and efficient therapeutic strategy.

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Posttransplant cyclophosphamide after allogeneic hematopoietic cell transplantation mitigates the immune activation induced by previous nivolumab therapy

Cited by 22 publications

References 15 publications

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

Immunotherapy use outside clinical trial populations: never say never?

Harnessing Treg Homeostasis to Optimize Posttransplant Immunity: Current Concepts and Future Perspectives

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