Managing Side Effects of Luspatercept

Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, led a roundtable discussion about the treatment paradigm for low-risk MDS and the side effect profile of luspatercept. The expert panel featured Christopher Benton, MD, of Rocky Mountain Cancer Centers; Jamile M. Shammo, MD, of Northwestern Feinberg School of Medicine; Tiffany Tanaka, MD, of the University of California San Diego; and Amer Zeidan, MBBS, MD, of Yale School of Medicine. 

Luspatercept is generally well tolerated. The safety profile of luspatercept is more comparable to erythropoiesis-stimulating agents (ESAs) than other, more myelosuppressive treatments used in MDS such as imetelstat and hypomethylating agents, said Dr. Zeidan. Luspatercept is associated most commonly with fatigue, but it can also cause hypertension, gastrointestinal side effects, and muscle or bone pain. 

With luspatercept, fatigue typically presents in the first few cycles and tends to improve if the patient has a hemoglobin response. Patients may need to discontinue luspatercept if fatigue does not improve, but that is not common, said Dr. Zeidan. Secondary causes of fatigue like iron deficiency anemia should also be ruled out. Similarly, while luspatercept can induce hypertension, Dr. Zeidan recommended that physicians rule out white-coat hypertension, separate hypertensive medications, or other causes before adjusting treatment. 

There are data associating thrombosis and blood clots with luspatercept, but most of these come from luspatercept in thalassemia populations, and Dr. Zeidan has not seen thrombosis or clots when using luspatercept in MDS in practice. The prescribing information for luspatercept calls to hold doses if patients have a hemoglobin above 12 g/dL, which may help mitigate any potential thrombosis or clotting risk.