Myelofibrosis is a myeloproliferative neoplasm with a poor survival rate, primarily characterized by anemia, splenomegaly, constitutional symptoms, bone pain, and cachexia. The only curative treatment is allogeneic peripheral stem cell transplantation, although it is associated with a non-negligible mortality and morbidity risk. JAK2 inhibitors help reduce spleen size and alleviate symptoms in these patients. The two most recent JAK2 inhibitors (pacritinib and momelotinib) may also confer erythropoietic benefits.
Despite therapeutic advances in multiple myeloma management, the disease remains incurable, largely due to the emergence of resistant tumor clones. Immunotherapy has made significant progress in recent years. In front-line therapy, the inclusion of monoclonal antibodies alters the outcomes for transplant-eligible patients, providing potential long-term disease control. In relapse, bispecific antibodies and CAR-T cells demonstrated notable efficacy in terms of survival and residual disease control, offering real hope for patients resistant to conventional treatments. These two aspects will be addressed in this article.
In patients presenting with venous or arterial thrombosis associated with thrombocytopenia, the presence of anti-PF4 antibodies and their properties (heparin dependence and platelet activation capacity) should be investigated. Widely adopted in congenital hemophilia, emicizumab, a bispecific antibody mimicking the action of factor VIII, is poised to become a first-line hemostatic treatment for patients with acquired hemophilia. These patients will benefit from better protection against bleeding, delaying the onset of severe and often deleterious immunosuppression in fragile patients. Certain intravenous iron formulations may lead to hypophosphatemia, a neglected but avoidable complication. For refractory forms of autoimmune thrombocytopenia, complement, Bruton's tyrosine kinase, CD38, and the neonatal Fc receptor represent promising therapeutic targets.
Keywords
Myelofibrosis, myeloproliferative syndrome, JAK2 inhibitor, multiple myeloma, immunotherapy, CAR-T cells, PF4, thrombocytopenia, acquired hemophilia, emicizumab, intravenous iron, hypophosphatemia, immune thrombocytopenic purpura, complement, neonatal Fc receptor, fragment