Symptomatic pseudo-progression followed by significant treatment response in two lung cancer patients treated with immunotherapy

Hochmair, Maximilian; Schwab, Sophia; Burghuber, Otto Chris; Krenbek, Dagmar; Prosch, Helmut

doi:10.1016/j.lungcan.2017.08.020

Cited by 44 publications

(30 citation statements)

References 8 publications

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“…Consideration should be given to the sites of active disease and specifically to whether immune activation, such as tumour flare 'pseu doprogression' , could compromise vital organ function (for example, of the airway or central nervous system (CNS)). Patients with active CNS pathology should be selected with caution, particularly for products associ ated with CRES [41][42][43] . When feasible, baseline evaluation by interdisciplinary team members, such as intensive care physicians and neurologists, could help to guide patient selection.…”

Section: Patient Selection and Evaluationmentioning

confidence: 99%

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

et al. 2018

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In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19 acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.

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Section: Patient Selection and Evaluationmentioning

confidence: 99%

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

et al. 2018

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“…Indeed, it was shown in melanoma trials that the brain objective response rate (ORR) decreased by 15% with the addition of corticosteroids during ICI treatment (10 vs 25%, extracranial and cranial comparable) [57]. Furthermore, the administration of ICI in patients with BM may be associated with pseudo-progression and subsequent symptom aggravation due to increased edema before actual tumor shrinkage [23,25,58]. This phenomenon may require symptomatic treatment with steroids which might influence the treatment potency [57].…”

Section: Rationale and Possible Concerns For Ici-based Treatment In Bmentioning

confidence: 99%

“…In ICI treated patients, pseudoprogression has been reported in glioblastoma but also in case reports on NSCLC and melanoma patients [23][24][25]85]. The iRANO criteria state that when a patient's clinical condition significantly declines combined with growth or new brain lesions, this should be called true progression and ICI should be discontinued.…”

Section: Response Measurementmentioning

confidence: 99%

“…Despite the high incidence of BM, patients with untreated and/or unstable BM were excluded from pivotal immune checkpoint inhibitors (ICI) NSCLC trials [12][13][14][15][16][17][18][19][20][21][22]. Reasons to exclude these patients were: the probable inability of ICI to cross the blood-tumor-barrier (BTB, the blood-brain barrier around the tumor) because of their size, the use of steroids to reduce BM symptoms which might abrogate an immune response and the risk of pseudoprogression which might cause aggravation of neurological symptoms [23][24][25]. Moreover, BM patients often need local therapies such as WBRT or SRT but there is a lack of data on safety when combining cranial radiation with ICI.…”

Section: Introductionmentioning

confidence: 99%

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Non-small cell lung cancer brain metastases and the immune system: From brain metastases development to treatment

Rassy

Botticella

Kattan

et al. 2018

Cancer Treatment Reviews

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Brain metastases (BM) are diagnosed frequently in non-small cell lung cancer (NSCLC) patients. Despite the high incidence of BM (up to 40% in unselected patients), patients with untreated and/or unstable BM were excluded from pivotal immune checkpoint inhibitors (ICI) NSCLC trials. Percentage of patients with stable and treated BM in these trials ranged from 9.1 to 14.7% and ICI benefit over chemotherapy was not always demonstrated. Only small trials have been completed that demonstrated ICI efficacy in locally untreated, selected BM patients. With 33%, cranial objective response rate (ORR) was comparable to extracranial ORR and responses were often durable. With the promising survival benefits of ICI, in daily practice also unstable and/or untreated BM patients will often receive treatment with ICI and extrapolating clinical trial data to these patients can be challenging. In this review, we will summarize the preclinical rationale and potential concerns for the use of ICI in BM patients. Furthermore, we will summarize BM subgroup data from the pivotal NSCLC trials, retrospective series, the NSCLC BM specific ICI trials and the use of cranial radiation and ICI. Last, we provide an overview of response measurement criteria and future directions.

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“…After investigating previous reports, we found a common point: the accompanying symptoms of disease progression are likely associated with serous effusion (Table 1). 7,8 We suggest that patients receiving immunotherapy who have radiographic progression accompanied by symptoms associated with serous effusion should continue immunotherapy while treating the effusion. All three patients presented here can be included in the scope of "pseudoprogressive" immunotherapy, 9 but do not represent the typical pseudoprogressive model.…”

Section: Discussionmentioning

confidence: 99%

Curative effect assessment of immunotherapy for non‐small cell lung cancer: The “blind area” of Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

et al. 2019

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Background Immunotherapy has considerably changed the treatment of lung cancer. As immunotherapy has a special mechanism of action, the disease remission that it can induce is unique. Recently, Immune Response Evaluation Criteria in Solid Tumors (iRECIST), which focus on assessing the apparent curative effect of immunotherapy, have become widely accepted. Based on iRECIST criteria, if the response to immunotherapy is determined to be immunity‐confirmed progressive disease or immunity‐unconfirmed progressive disease, and the Eastern Cooperative Oncology Group score is worse than before treatment, immunotherapy should be discontinued. We report two immunity‐confirmed progressive disease cases after pembrolizumab treatment and one immunity‐unconfirmed progressive disease case after nivolumab treatment. All three patients benefited from continued immunotherapy, which indicates that the iRECIST criteria may have limitations in assessing the efficacy of immunotherapy for non‐small cell lung cancer patients.

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Symptomatic pseudo-progression followed by significant treatment response in two lung cancer patients treated with immunotherapy

Cited by 44 publications

References 8 publications

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

Non-small cell lung cancer brain metastases and the immune system: From brain metastases development to treatment

Curative effect assessment of immunotherapy for non‐small cell lung cancer: The “blind area” of Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

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