Method for treating immune toxicities induced by immune checkpoint inhibitors
The invention relates to the use of a JAK inhibitor for treating or preventing adverse events in patient treated with an immune checkpoint inhibitor, or for treating cancer in combination with an immune checkpoint inhibitor.
1 . A method for treating or preventing an immune-related adverse event, wherein the immune-related adverse event is induced by treatment with an immune checkpoint inhibitor, the method comprising administering a therapeutically effective amount of ruxolitinib to a subject in need thereof;
wherein the adverse event is not toxidermia, colitis, or arthritis.
2 . The method of claim 1 , wherein the immune-related adverse event is an immune-mediated disease selected from myocarditis, pneumonitis, hepatitis, hypophysitis, neurologic adverse effect, adrenal adverse effect, myositis, hematologic adverse effect, pancreatitis, endocrinological adverse effect, nephritis, or a combination thereof.
3 . The method of claim 1 , wherein the immune-related adverse event is a de novo event, not related to a preexisting immune condition of the subject before treatment with the immune checkpoint inhibitor.
4 . The method of claim 1 , wherein the immune-related adverse event is an immune-mediated myotoxicity.
5 . The method of claim 4 , wherein the immune-mediated myotoxicity is fulminant myocarditis or fulminant respiratory muscle myositis involving the subject's diaphragm.
6 . The method of claim 1 , wherein the immune checkpoint inhibitor is selected from PD-1 inhibitors, PD-L1 inhibitors, anti-CTLA4, or a combination thereof.
7 . The method of claim 1 , wherein the immune checkpoint inhibitor is a PD-1 inhibitor selected from nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, cemiplimab, toripalimab, spartalizumab, cetrelimab, sasanlimab, or a combination thereof.
8 . The method of claim 1 , wherein the immune checkpoint inhibitor is a PD-L1 inhibitor selected from atezolizumab, avelumab, durvalumab, or a combination thereof.
9 . The method of claim 1 , wherein the immune checkpoint inhibitor is an anti-CTLA4 selected from ipilimumab, tremelimumab, or a combination thereof.
10 . The method of claim 1 comprising multiple administrations of the ruxolitinib to the subject.
11 . The method of claim 1 , wherein the ruxolitinib is administered to the subject over a period of three weeks to twenty-four weeks.
12 . The method of claim 1 , wherein the ruxolitinib is administered to the subject in a slow-release composition.
13 . The method of claim 1 , further comprising administering a therapeutically effective amount of an immunosuppressant with the ruxolitinib.
14 . The method of claim 13 , wherein the immunosuppressant is a glucocorticoid, a CTLA4 agonist, or a combination thereof.
15 . A method for treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of ruxolitinib and a therapeutically effective amount of an immune checkpoint inhibitor, wherein the method prevents occurrence or recurrence of a severe immune-related adverse event related to use of the immune checkpoint inhibitor in the treatment of cancer.
16 . The method of claim 15 , further comprising administering to the subject a therapeutically effective amount of an immunosuppressant.
17 . The method of claim 15 , wherein the ruxolitinib and the immune checkpoint inhibitor are administered separately or sequentially.
18 . The method of claim 15 , wherein the immune checkpoint inhibitor is selected from nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, cemiplimab, toripalimab, spartalizumab, cetrelimab, sasanlimab, atezolizumab, avelumab, durvalumab, ipilimumab, tremelimumab, or a combination thereof.
19 . The method of claim 13 , wherein the immunosuppressant is abatacept.
20 . The method of claim 16 , wherein the immunosuppressant is abatacept.
21 . A method of treating or preventing an immune-related adverse event induced by a treatment with an immune checkpoint inhibitor in a subject comprising administering to the subject ruxolitinib, abatacept, and a corticosteroid, wherein the administering is simultaneous, separate, or sequential.