A Trial of Selinexor, Ruxolitinib and Methylprednisolone

Selinexor, a first-in-class, oral selective exportin 1 (XPO1) inhibitor, has shown promise in pre-clinical and clinical studies. It functions by inhibiting the nuclear export protein XPO1, resulting in the accumulation of tumor suppressor proteins and inhibition of oncoprotein mRNAs, which is selectively lethal to myeloma cells. Selinexor has demonstrated activity in combination with various drugs, including glucocorticoids and proteasome inhibitors, leading to its FDA approval for the treatment of relapsed or refractory multiple myeloma.

Selinexor, a first-in-class, oral selective exportin 1 (XPO1) inhibitor, has shown promise in pre-clinical and clinical studies. It functions by inhibiting the nuclear export protein XPO1, resulting in the accumulation of tumor suppressor proteins and inhibition of oncoprotein mRNAs, which is selectively lethal to myeloma cells. Selinexor has demonstrated activity in combination with various drugs, including glucocorticoids and proteasome inhibitors, leading to its FDA approval for the treatment of relapsed or refractory multiple myeloma. Ruxolitinib, an oral JAK1/2 inhibitor, has been approved by the FDA for myelofibrosis treatment. Preliminary experiments have shown that Ruxolitinib, in combination with lenalidomide and dexamethasone, effectively inhibits MM cell proliferation. Additionally, the combination of Ruxolitinib and dexamethasone has demonstrated enhanced anti-MM effects. Clinical results indicate that Ruxolitinib in combination with steroids is well-tolerated in heavily treated MM patients. This proposed study aims to investigate the efficacy of a lower dose of Selinexor in combination with Ruxolitinib and methylprednisolone for patients with relapsed/refractory multiple myeloma. The study builds on the existing evidence of the individual and synergistic effects of Selinexor and Ruxolitinib, both in preclinical and clinical settings and seeks to provide a potential new treatment option for MM patients.