How We Treat Anemia in Myelofibrosis [Review].

Here are some relevant points on the treatment of anemia in myelofibrosis.

Key points:  

●       The patient with myelofibrosis and anemia is at intermediate or high risk?: Consider allogeneic hematopoietic cell transplantation.

●       Does the patient have isolated anemia without significant symptoms of splenomegaly? Measure serum erythropoietin (EPO); if it is ≤125 U/L, the patient could benefit from erythropoiesis-stimulating agents. If EPO >126 U/L, consider luspatercept, danazol, or lenalidomide (for patients with myelofibrosis-associated anemia and del(5q)).

●       Does the patient have symptoms or splenomegaly that require Janus kinase (JAK) inhibition? Consider adding danazol, erythropoiesis-stimulating agents, or luspatercept.

●       Is the patient already on a JAK inhibitor, and if so, is it optimized? If so, switch to another JAK inhibitor, such as momelotinib or pacritinib.

See Figure 4 in the original article.

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation [Phase 2b clinical trial].  

Highlights:

Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban.

In this study (AZALEA–TIMI 71), 1287 patients (median age 74 years) underwent randomization in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation) at a dose of 150 mg or 90 mg once monthly, administered in a blinded fashion, or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary endpoint was major or clinically relevant nonmajor bleeding.

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial [Phase III clinical trial].

Highlights:

Induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) yielded the highest pre-transplant minimal residual disease (MRD)-negativity rates ever reported in transplant-eligible newly diagnosed multiple myeloma (MM) patients. The favorable efficacy-toxicity balance with IsaKRD induction portends promising outcomes with long-term follow-up of the MIDAS cohort.

The phase III IFM2020-02-MIDAS study is an ongoing randomized, open-label, active-controlled, parallel-group, multicenter, phase III trial for patients with previously untreated MM. Here, the authors report the safety and efficacy outcomes of six 28-day cycles of IsaKRD, between December 2021 and July 2023.

JAK1/2 inhibitor ruxolitinib for treating systemic chronic active Epstein-Barr virus disease  [Phase 2 clinical trial]. 

Highlights: 

●       Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare intractable EBV-positive T-cell or natural killer (NK)-cell lymphoid neoplasm with systemic inflammation. The only curative treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT).

●       Disease activity, defined by multiple inflammatory symptoms is associated with poor survival. In sCAEBV, the signal transducer and activator of transcription 3 (STAT3) is constitutively activated in EBV-infected T and NK cells and promotes their activation and survival. Ruxolitinib, a Janus kinase 1/2 inhibitor, suppresses the STAT3 activation in vitro, suggesting its clinical potential.

●       Ruxolitinib resulted in complete response (CR), which is the disappearance of disease activity in 22.2% of patients (2/9) with sCAEBV. No patient showed hematopoietic toxicity nor disease progression. Ruxolitinib is a potent treatment drug that may improve allo-HSCT outcomes by suppressing the disease activity of sCAEBV.

In this study, nine patients received ruxolitinib, and seven patients completed the study. After ruxolitinib treatment, seven patients received allo-HSCT and five of them achieved CR with undetectable EBV-DNA levels in whole blood.

Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia [Phase 2 clinical trial].  

Highlights: 

●       Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, mainly attributable to complement activation resulting in intravascular and extravascular hemolysis.

●       Pegcetacoplan is a subcutaneously administered C3-targeted therapy which may be suitable for treating CAD and wAIHA.

●       This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective for patients with CAD and wAIHA.

In this open-label phase 2 study, analyses were conducted in 2 cohorts, 1 for patients with CAD (n=13) and the other for those with wAIHA (n=11). In each cohort, patients were randomly assigned to receive pegcetacoplan for up to 48 weeks. Safety end points included the incidence and severity of treatment-emergent adverse events, as well as adverse events of special interest. Efficacy endpoints included change from baseline in hemoglobin, lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and functional assessment of chronic illness therapy-fatigue scale.