Abscopal effect in a Hodgkin lymphoma patient treated by an anti-programmed death 1 antibody

Michot, Jean‐Marie; Mazeron, R.; Dercle, Laurent; Ammari, Samy; Canova, C.-H.; Marabelle, Aurélien; Rose, Shelonitda; Rubin, Eric H.; Deutsch, Éric; Soria, Jean‐Charles; Ribrag, Vincent; Lévy, Antonin

doi:10.1016/j.ejca.2016.06.017

Cited by 56 publications

(21 citation statements)

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“…In addition to increasing neoantigens, radiation may increase immune activation and response to checkpoint blockade through other means. There have been several intriguing cases reported in which localized radiation along with checkpoint blockade has resulted in an abscopal effect in which there is regression of a metastatic site that is outside of the radiation field (Hiniker et al, 2012;Michot et al, 2016;Postow et al, 2012;Stamell et al, 2013).…”

Section: Figure 2 Antigenic Milieu Of Sporadic Pediatric Cancers Spmentioning

confidence: 99%

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

2017

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Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers. Intense efforts are underway to enhance the effectiveness of pediatric cancer immunotherapies through improved engineering of synthetic immunotherapies and by combining these with agents designed to amplify immune responses.

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Section: Figure 2 Antigenic Milieu Of Sporadic Pediatric Cancers Spmentioning

confidence: 99%

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

2017

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“…In 2016, the LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) introduced the term indeterminate response (IR)-instead of progression-as the time interval until a biopsy or subsequent imaging confirmed either a pseudoprogression or a true progression (18), restraining clinicians to a wait-and-see strategy. Additionally, new immune patterns were described such as abscopal effect (i.e., a tumor's antigens released by radiotherapy lead to the regression of metastatic cancer size and metabolism at a distance from the irradiated site due to the enhancement of the diversity of the T-cell receptor) (19) and hyperprogression (i.e., anti-PD1 initiation leads to a paradoxal increase in tumor growth rate) (20).…”

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confidence: 99%

¹⁸F-FDG PET and CT Scans Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti–Programmed Death 1 Immune Checkpoint Inhibitor

et al. 2017

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The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti-programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19-69 y). The median previous lines of therapy was 6 (range, 3-13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. F-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUV, metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Three-monthF-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis.

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“…Radiation therapy is generally considered to be a local treatment. However, occasionally response in tumor deposits outside the treated volume has been reported, thus suggesting a systemic effect [63][64][65][66]. The phenomenon has been described as an abscopal (out of field) effect [67][68][69].…”

Section: Immunological Effects Of Radiation Therapymentioning

confidence: 99%

Rationale for combination of radiation therapy and immune checkpoint blockers to improve cancer treatment

2019

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Radiation therapy for cancer is considered to be immunosuppressive. However, the cellular response after radiation therapy may stimulate or suppress an immune response. The effect may vary with the tumor type and occasionally tumor regressions have been observed outside the irradiated volume, both in animal studies and in the clinic. A renewed interest in the role of immunity for the observed effect of radiation came with the current recognized role of immune checkpoint blockers (ICBs) for control of selected cancer types. We therefore here review preclinical studies and clinical reports on the interaction of ICBs and radiation as a basis for further clinical trials. Some tumor types where the combination of these modalities seems especially promising are also proposed. ARTICLE HISTORY

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Abscopal effect in a Hodgkin lymphoma patient treated by an anti-programmed death 1 antibody

Cited by 56 publications

References 9 publications

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

¹⁸F-FDG PET and CT Scans Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti–Programmed Death 1 Immune Checkpoint Inhibitor

Rationale for combination of radiation therapy and immune checkpoint blockers to improve cancer treatment

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Abscopal effect in a Hodgkin lymphoma patient treated by an anti-programmed death 1 antibody

Cited by 56 publications

References 9 publications

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

18F-FDG PET and CT Scans Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti–Programmed Death 1 Immune Checkpoint Inhibitor

Rationale for combination of radiation therapy and immune checkpoint blockers to improve cancer treatment

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¹⁸F-FDG PET and CT Scans Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti–Programmed Death 1 Immune Checkpoint Inhibitor