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Samantha Rae Hopkins (Maiden Name Kestenbaum)
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P78 - Immunotherapy (Phase II/III Trials) - Immune Checkpoint Inhibitor Single Agent (ID 255)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P78.11 - Immunotherapy-Induced Coeliac Disease in the Curative Lung Cancer Patient on Adjuvant Durvalumab (ID 3044)
00:00 - 00:00 | Presenting Author(s): Samantha Rae Hopkins (Maiden Name Kestenbaum)
- Abstract
Introduction
The PACIFIC study led to the approval of durvalumab in the adjuvant setting for patients with unresectable, stage III non-small cell lung cancer (NSCLC) after chemo-radiotherapy (CRT)1, and whose tumours express programmed death-ligand-1 (PDL-1) in >1% of cells. PDL-1 is an immune regulating molecule which has been hypothesized to aid neoplastic lesions to evade the host’s immune system. Durvalumab is a human monoclonal IgG1 antibody which blocks PDL-1 on cytotoxic T-cells, leading to increased cytotoxic T-cell proliferation and activity, and cytokine production1. The activation of T-cells can lead to immune-related adverse events (IrAEs).
Methods
A 68-year-old female with stage III NSCLC received adjuvant durvalumab. Her PDL-1 was 90-100%. After four cycles of durvalumab, she presented with Grade 2 diarrhoea2. She was admitted to hospital and started on prednisone 50mg (1mg/kg). After three days, she had a sigmoidoscopy which appeared macroscopically normal. Biopsies showed a non-specific increase in intraepithelial lymphocytes. The diarrhoea resolved, and she was discharged on a weaning regime of prednisolone for presumed immune checkpoint inhibitor(ICPi)-induced colitis.
Two months later, she represented with Grade 3 diarrhea2. Examination and imaging was normal. Positive findings were an elevated serum anti-transglutaminase (anti-tTG) IgA level at 10.2unit/mL, low folic acid and low vitamin D. An oesophagogastroduodenoscopy (OGD) showed scalloping of the duodenum and biopsies showed marked villous blunting, chronic inflammation of the lamina propria and increased intraepithelial lymphocytes; all findings consistent with the diagnosis of CD. She was started on a lifelong gluten-free (GF) diet and given a weaning course of oral prednisone with the intention of improving her symptoms rapidly. Her diarrhoea immediately improved and a decision was made to restart immunotherapy once the steroids were complete. She did not report recurrence of her symptoms following an additional seven cycles of durvalumab therapy whilst on a GF diet. The anti-tTG IgA normalised after 3 months.
Results
This case highlights a rare IrAE of CD presenting during ICPi treatment. Durvalumab may have unmasked previously undiagnosed CD. Alternatively, the patient may have developed CD de-novo, as a direct consequence of ICPi treatment.
The detection of rare toxicities requires a large number of patients to be treated with ICPis, therefore rarer toxicities are often identified post licensing, when the number of patients receiving these drugs increases exponentially. There are three published cases of patients receiving immunotherapy developing CD after the commencement of the drug but the exact incidence of this IrAE and exact underlying mechanism for the development of CD secondary to immunotherapy is unknown.
Conclusion
This is the first reported case of CD arising following ICPis in both the adjuvant lung cancer setting, and with the drug durvalumab. A new diagnosis of CD will have long-term consequences for this patient who may have been cured with CRT alone. However, the majority of patients with stage III NSCLC have disease progression despite CRT and therefore the addition of immunotherapy in improving survival is significant. Although diarrhoea due to CD is an exceptional IrAE, symptoms can resolve quickly once a diagnosis is made and a GF diet commenced.
