Background/Purpose: Treatment of irAEs is a balance of suppressing irAE-associated hyper-inflammation without inhibiting anti-tumoral effects of ICI. Treatment of grade 3/4 irAEs is most challenging and guidelines from multiple oncology groups recommend holding or permanently discontinuing ICIs and treating with escalating immunosuppression until resolved, followed by switch to conventional anti-cancer therapies. Such strategies are effective for mild and self-limiting irAEs and often allows resumption of ICI after resolution but can be highly problematic for rheumatic irAEs which are often chronic as well as more severe and refractory than non-rheumatic irAEs. For these patients a maintenance regimen of chronic targeted therapy followed by resumption of ICI therapy theoretically may allow ongoing irAE control while sparing the anti-tumoral potential of ICI with select immunomodulation. Unfortunately, the published experience of such combined therapies is extremely limited. We now report our experience of sustained targeted and ICI therapy in 9 patients.

Methods: All patients receiving concomitant biologic therapy and ongoing ICI seen in the Cleveland Clinic Department of Rheumatic and Immunologic Diseases and the Jewish General Hospital Department of Oncology at McGill University were included and retrospectively assessed for efficacy, tolerability, safety and effect on tumor progression.

Results: Nine patients received ICI concurrently with biologic therapy (6 melanoma, 1 gastric carcinoma, 2 renal cell). Three were treated with ipilimumab/nivolumab, 4 with nivolumab and 2 with pembrolizumab. Two of the nivolumab patients had previously received ipilimumab/nivolumab. Five patients had ICI-related inflammatory arthritis, 1 had pre-existing rheumatoid arthritis, and 3 had refractory ICI-related colitis. Three patients received concurrent treatment with adalimumab, 1 tocilizumab, 1 tofactinib and 4 infliximab. Prior to initiation of biologic, ICI was held for irAE in 8, all received systemic glucocorticoids and 3 methotrexate. The average duration of combined treatment with ICI and biologic was 4.5 months (range 1-11 months). irAEs were controlled (low disease activity) in 7/9 while 2/9 had moderate disease activity. Regarding tumor outcomes, 5 patients have stable disease, and 4 had disease progression. There were no adverse events, including serious or opportunistic infections known to be associated with biologic therapy.

Conclusion: This limited experience suggests that combining ongoing targeted therapies with ICI is possible with no clear serious adverse events noted to be directly associated with targeted therapies. The effect of combining such therapies on tumor response remains unclear and will require prospective clinical trials.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concomitant-targeted-therapy-with-ongoing-immune-checkpoint-inhibitor-ici-therapy-for-severe-immune-related-adverse-events-iraes-clinical-experience-from-two-centers/