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Managing Malignancy in IBD Patients on Biologics: Case Studies and Clinical Considerations

Explore the impact of IBD medications on cancer risk, particularly skin cancers, lymphoma, and solid tumors. Understand the delicate balance between continuing or discontinuing medications when malignancy develops. Get insights from experts and crucial research findings.

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Managing Malignancy in IBD Patients on Biologics: Case Studies and Clinical Considerations

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  1. Pro: An IBD patient on a biologic and/or an immunomodulator, who develops a malignancy:skin cancersolid tumorlymphomamay continue or restart these medications, if needed to treat IBD Miguel Regueiro, MD, FACG, AGAFProfessor of MedicineClinical Head, IBD CenterUniversity of Pittsburgh Medical Ctr

  2. Do I really have a chance of winning a debate when my side is to continue meds when CA develops?

  3. Thank you for slides • Jim Lewis • Jean Fred Colombel • Corey Siegel (also for photos of Tom!)

  4. Important questions in pts who develops cancer on IBD meds: Did the medicine cause the cancer? What is the risk of: - continuing the med in terms of worsening cancer or - discontinuing the med in terms of worsening IBD?

  5. Let’s consider three types of cancer: Skin Cancer Lymphoma Solid Tumors

  6. Case • 50 year old male • 30 year history of small bowel Crohn’s • 1 prior bowel resection • Current meds – 6MP + Adalimumab • 3 BM per day • Colonoscopy – few scattered aphthous ulcers (i1) in the neo-TI

  7. Case (cont) • 2 years prior diagnosed with Non Melanoma Skin Cancer (Basal Cell Ca) • 2 weeks ago newly diagnosed with Squamous Cell Cancer

  8. Is skin cancer caused by or are patients at increased risk from… azathioprine/6MP Methotrexate antiTNFs

  9. Thiopurines and Skin Cancer NMSC MELANOMA Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20 Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8 Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181

  10. Timing of Thiopurines and NMSC (esp. older ages) CESAME SIR and 95% CI Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8

  11. Anti-TNF and Skin Cancer (IBD data) NMSC MELANOMA NR Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20 Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8 Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181

  12. Clinical Questions • Is skin cancer risk increased by therapy? • Thiopurines – yes • Methotrexate – don’t know, probably not • Biologics – no NMSC, maybe melanoma • If so, does the risk of continuing therapy outweigh the benefits? • In this case – consider stopping thiopurine • Uncertain if risk will decline • Annual skin exam and regular use of sunscreen and hats

  13. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  14. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  15. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  16. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  17. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  18. Lymphoma

  19. Questions • Does immunosuppressant therapy increase the risk of lymphoma? • Do the benefits outweigh the risks? • What do you do when a lymphoma develops in the setting of IBD meds?

  20. AZA/6-MP are probably related to Lymphoma (Meta-analysis): SIR 4.06 SIR = 4.06, 95% CI 2.01 – 7.28 Kandiel A et al. Gut. 2005:54:1121-25

  21. CESAME – 6MP/AZA OnlyLymphoma: HR 5.3 Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7

  22. Risk of NH Lymphoma with anti-TNF + IM treatment for Crohn’s Disease: A Meta-Analysis • 8905 patients representing 20,602 pt-years of exposure • 13 Non-Hodgkin’s lymphomas  • Mean age 52, 62% male • 10/13 exposed to IM* (really a study of combo Rx) 6.1 per 10,000 pt-years Siegel et al, CGH 2009;7:874. *not reported in 2

  23. CESAME – Combo 6MP/AZA and antiTNF: SIR = 10.2 Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7

  24. Clinical Questions • Does immunosuppressant therapy increase the risk of lymphoma? • Thiopurines – yes, but risk may revert after discontinuation • antiTNFs – Probably not • Combination – Yes and probably more than monotherapy

  25. Risk:Benefit Ratio

  26. Hepatosplenic T Cell Lymphoma • 41 cases from FDA AERS among patients with IBD1 • Thiopurine alone 17 • Anti-TNF alone 1 • Combination therapy 23 • Characteristics2 • Median age 22.5 (12 – 58) • 93% male • Median time since initiation of thiopurines ~6 years • Deepak P. Am J Gastroenterol 2013; 108:99–105 • Kotlyar D. Clin Gastroenterol Hepatol 2011;9:36–41

  27. Lymphoma - Number Needed to Harm ‡ Kandiel A et al. Gut. 2005:54:1121-25 * 5 year survival = 68% for NHL, 85% for HD, estimated at 75% for this example ‡ Kandiel A et al. Gut. 2005:54:1121-25 * 5 year survival = 68% for NHL, 85% for HD, estimated at 75% for this example

  28. What to do if lymphoma develops while taking IMM/antiTNF?

  29. Case – Stop or Continue? • 39 yo male CD in remission on 6MP/IFX for 8 yrs. • Now with weight loss, sweats, and low grade fevers

  30. Crohn’s ds case: NHL while taking 6MP/IFX.

  31. After consulting with the oncologist…. …we stopped the 6MP/antiTNF, but after 3 months of chemorx, the antiTNF was resumed. We did not restart the 6MP.

  32. On CT: Hepatosplenic T cell lymphoma – enlarged spleen, otherwise nonspecific. Thiopurine must be stopped!

  33. Solid Tumors

  34. Case Continue or Stop? • 58 yo female with severe UC who has been on IFX/6MP (50mg/d) for past 1yr • Just diagnosed with intraductal breast CA (T1N0MX) • Strong FHx breast CA, pt opts for bilateral mastectomy • After consultation with oncology, the decision is to cont meds

  35. No clear association between thiopurines/antiTNFs and solid tumors in IBD

  36. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  37. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  38. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  39. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  40. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  41. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  42. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  43. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  44. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  45. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  46. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  47. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  48. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  49. Should we continue or stop IBD meds if a cancer develops? Depends on IBD

  50. Deep Remission If in deep remission, maybe stopping IBD meds is ok and not restarting them

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