P33 Spontaneous regression of confirmed diffuse large B-cell lymphoma after withdrawal of long-term methotrexate and infliximab therapy for rheumatoid arthritis, with concurrent discovery of rare high-grade urothelial carcinoma

Abstract

Abstract Background A 73 year old man was diagnosed with diffuse large B-cell lymphoma germinal centre phenotype, after presenting with a 86x70x45mm right anterior chest wall lesion. CT CAP showed no further lymphadenopathy but identified an additional solid mass in the right ureter. The patient had been on methotrexate for 15 years and infliximab for 13 years for well controlled rheumatoid arthritis, and these were both discontinued on diagnosis of lymphoma. Within three weeks of discontinuation, the lymphomatous mass had clinically noticeably shrunk, confirmed radiologically, and on PET evaluation showed just low-grade avidity. However, the ureteric tumour was avid on PET, suggestive of second pathology. Biopsy proved high grade urothelial carcinoma with neuroendocrine differentiation. Chemotherapy to treat the urothelial carcinoma was identified as a priority, and carboplatin and etoposide chemotherapy was commenced which also has activity in lymphoma. Radiotherapy will be considered in the future, if indicated following further imaging. Methods A literature search was conducted on occurrence of lymphoma and urothelial carcinoma with anti-TNFα biologics. Results The link between methotrexate and increased risk of lymphoma is well covered in literature. Anti-TNFα biologic drugs have also been linked to lymphoma, but definitive causality is difficult to establish due to low numbers of cases and confounding factors. No cases were found in literature to associate anti-TNFα drugs with urothelial, transitional cell or neuroendocrine carcinomas. Eight case studies were found which show a temporal link between discontinuation of anti-TNFα and regression of lymphoma. Of these, six cases reported regression following withdrawal of infliximab. One case involved infliximab monotherapy, three had combination therapy with methotrexate, and two with azathioprine. One case reported discontinuation of adalimumab, with continuation of methotrexate. Histology showed two cases of low grade lymphoma, two case of Hodgkin’s lymphoma, and four cases of diffuse large B Cell non-Hodgkin’s lymphoma, similar to our patient case. Conclusion This patient presented with two synchronous tumours: diffuse large B cell NHL and high grade neuroendocrine carcinoma of urothelial tract. Whereas lymphoma regressed on withdrawal of methotrexate and infliximab, there was no change in the urothelial malignancy. Lymphoma regression allowed the urothelial malignancy to take priority for oncological therapy. It can be concluded that withdrawal of anti-TNF agents can allow spontaneous regression of lymphoma, and this can modify patient treatment plans. Disclosures B.A. Jones None. A. O'Callaghan None. E.V. Ross None. A. Razack None. E. Wong None.