Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report

Eguchi, Shimpei; Shinkawa, Hiroji; Sato, Yasunori; Nakai, Kozo; Takemura, Shigekazu; Tanaka, Shogo; Amano, Ryosuke; Kimura, Kenjiro; Ohira, Go; Nishio, Kenji; Kinoshita, Masahiko; Tauchi, Jun; Miyazaki, Toru; Ishihara, Atsushi; Shirai, Daisuke; Kubo, Shoji

doi:10.1007/s12328-021-01396-5

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…Late-onset CIP remains an under-recognized and complex diagnostic challenge. The lasting effects of immunotherapy, even after ICI withdrawal, have been verified by several studies (47)(48)(49)(50) and may be associated with the underlying mechanism of immunological 'memory' (48). If a long-term immunological 'memory' with a positive outcome does exist, it may also have implications for late-occurring T cell-mediated toxicities (22,27).…”

Section: Discussionmentioning

confidence: 86%

Late‑onset immune checkpoint inhibitor‑related pneumonitis after cessation of sintilimab: A case report and literature review

Yin

Yan

et al. 2023

Exp Ther Med

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Immune-related adverse events following treatment with immune checkpoint inhibitors (ICIs) can occur at any time during therapy, with onset occurring most frequently during the first 3 months of treatment. However, they rarely occur after treatment cessation. An awareness of delayed immune-related events following the termination of immunotherapy is paramount for optimal tumour management. The present study reports a case of a 69-year-old male patient with right lung adenocarcinoma. He suffered from psoriasis for ~40 years and was suspected of developing immune checkpoint inhibitor-related pneumonitis (CIP) 6 months after the cessation of treatment with the anti-programmed cell death-1 receptor antibody sintilimab. The present case study is, to the best of our knowledge, the first case of late-onset CIP after the cessation of sintilimab. Subsequently, the report also reviews previously reported cases of late-onset CIP after the cessation of ICI treatment. The present report highlights the finding that CIP can develop, although rarely reported, months or even years after the termination of immunotherapy. Therefore, CIP should always be considered as one of the possibilities and addressed accordingly once the pulmonary infection is ruled out. Careful monitoring, timely diagnosis and administration of corticosteroids are essential in controlling this condition, particularly for patients with pre-existing autoimmune diseases.

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Section: Discussionmentioning

confidence: 86%

Late‑onset immune checkpoint inhibitor‑related pneumonitis after cessation of sintilimab: A case report and literature review

Yin

Yan

et al. 2023

Exp Ther Med

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“…Reference lists of the 139 eligible articles were also screened for additional articles, and 77 articles met the eligibility criteria after screening. Among these, 70 articles reporting clinical data from 127 individual patients were reviewed to include in the analytic component of the systematic review. The 7 other articles provided predominantly summarized data, with limited and inconsistent data from individual patients.…”

Section: Resultsmentioning

confidence: 99%

Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With Cancer

et al. 2022

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IMPORTANCEThere is limited information on immune checkpoint inhibitor-induced bullous pemphigoid (ICI-BP) in patients with cancer, with most existing studies being case reports or small case series from a single institution. Prior review attempts have not approached the literature in a systematic manner and have focused only on ICI-BP secondary to anti-programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) therapy. The current knowledge base of all aspects of ICI-BP is limited.OBJECTIVE To characterize the risk factors, clinical presentation, diagnostic findings, treatments, and outcomes of ICI-BP in patients with cancer as reported in the current literature.EVIDENCE REVIEW A systematic review was performed using PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Articles reporting data on individual patients who met preestablished inclusion criteria were selected, and a predefined set of data was abstracted. When possible, study results were quantitatively combined.FINDINGS In total, 70 studies reporting data on 127 individual patients undergoing ICI therapy for cancer (median [IQR] age, 71 [64-77] years; 27 women [21.3%]) were included. In pooled analyses, patients ranged in age from 35 to 90 years. Immune checkpoint inhibitor-induced bullous pemphigoid often occurred during the course of anti-PD-1, PD-L1, or cytotoxic T lymphocyte-associated antigen 4 therapy but was also found to develop up to several months after treatment cessation. Prodromal symptoms, such as pruritus or nonspecific skin eruptions, were found in approximately half of the patient population. Histopathologic or serologic testing, when undertaken, was a helpful adjunct in establishing diagnosis. Treatment with immunotherapy was discontinued after ICI-BP development in most patients. The most common treatments were systemic and topical corticosteroids. Steroid-sparing therapies, such as antibiotics and other systemic immunomodulators, were also used as adjuvant treatment modalities. Biologic and targeted agents, used predominantly in cases refractory to treatment with corticosteroids, were associated with marked symptomatic improvement in most patients. CONCLUSIONS AND RELEVANCEThe results of this systematic review suggest that ICI-BP often poses a therapeutic challenge for patients with cancer who are receiving immunotherapy. Further research on the early recognition, diagnosis, and use of targeted treatment modalities will be essential in developing more personalized treatment options for affected patients while minimizing morbidity and mortality.

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“…ICIs, including pembrolizumab, inhibit PD-1/programmed death ligand 1 (PD-L1) and exert antitumor effects through T-cell activation; therefore, immune-related adverse events (irAEs), such as dysthyroidism, which are not observed after the administration of conventional cytotoxic anticancer drugs, need to be considered. The administration of pembrolizumab was previously discontinued at an early stage due to adrenal insufficiency in a patient with renal pelvic cancer ( 8 ), diabetic ketoacidosis in a patient with pancreatic cancer ( 9 ), and bullous pemphigoid in a patient with intrahepatic cholangiocarcinoma ( 10 ); however, its antitumor effects persisted. To the best of our knowledge, a similar case report has not yet been published in the malignant gynecological tumor field.…”

Section: Discussionmentioning

confidence: 99%

Durable response after the discontinuation of pembrolizumab treatment due to an adverse event in a patient with advanced endometrial cancer: A case report

et al. 2022

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The persistence of antitumor effects has been reported after the completion of treatment with immune checkpoint inhibitors (ICIs) for various types of carcinoma, such as malignant melanoma, exhibiting a durable response. A durable response has also been noted after the discontinuation of treatment at an early stage due to adverse events, including in renal pelvic cancer, pancreatic cancer and intrahepatic cholangiocarcinoma; however, to the best of our knowledge, a similar case report has not yet been published in the malignant gynecological tumor field. The present study described a patient with refractory advanced endometrial cancer in whom the administration of pembrolizumab was discontinued after the completion of the 7th course due to renal dysfunction; however, persistent tumor-reducing effects and decreases in the levels of tumor markers were noted for more than 18 months after the cessation of treatment. Pembrolizumab may be continuously administered to some patients for a long period, whereas a durable response is achieved by others even after its discontinuation at an early stage; therefore, difficulties are associated with selecting an appropriate duration of administration. Further studies are required to search for biomarkers that facilitate high-accuracy effect predictions, and to establish an optimal administration period in consideration of specific adverse reactions to ICIs and cost-effectiveness.

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Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report

Cited by 7 publications

References 26 publications

Late‑onset immune checkpoint inhibitor‑related pneumonitis after cessation of sintilimab: A case report and literature review

Late‑onset immune checkpoint inhibitor‑related pneumonitis after cessation of sintilimab: A case report and literature review

Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With Cancer

Durable response after the discontinuation of pembrolizumab treatment due to an adverse event in a patient with advanced endometrial cancer: A case report

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