Darzalex Faspro (daratumumab and hyaluronidase-fihj)

The first FDA-approved treatment for adults with newly diagnosed light chain (AL) amyloidosis. Used in combination with bortezomib, cyclophosphamide, and dexamethasone (a regimen called Dara-VCd), it targets the plasma cells that produce the misfolded light chains that damage organs in AL amyloidosis.

AL amyloidosis is driven by abnormal plasma cells in the bone marrow that produce misshapen light chain proteins. Those proteins clump together and deposit in organs like the heart and kidneys, eventually causing them to fail. Darzalex Faspro is an antibody that latches onto CD38, a marker found at high levels on those abnormal plasma cells, and signals the immune system to destroy them. Reducing the plasma cell population reduces the supply of damaging light chains.

In AL amyloidosis, common side effects include upper respiratory infection, diarrhea, swelling in the arms or legs, constipation, fatigue, nerve tingling or numbness, nausea, trouble sleeping, shortness of breath, and cough. Allergic and other reactions to the injection can happen, most often with the first dose, and can rarely be severe or life-threatening, so medicines are given 1 to 3 hours before each dose to lower the risk. The label also warns about sudden eye problems, such as nearsightedness or a type of glaucoma. Serious risks include serious or fatal heart problems in people with AL amyloidosis, serious infections, low white blood cell and platelet counts, and reactivation of hepatitis B. It also interferes with blood bank tests, so tell the transfusion center you take it before any transfusion. It can harm an unborn baby, so women who could become pregnant should use effective birth control during treatment and for 3 months after the last dose. Patients with significant pre-existing heart involvement (Mayo stage IIIB or NYHA class IIIB/IV cardiac disease) were excluded from the pivotal trial and the label warns against use in that population outside of controlled studies.

Given as a subcutaneous injection in the abdomen over about 3-5 minutes, much faster than the original IV daratumumab which can take several hours. In AL amyloidosis it is dosed weekly for the first two cycles, then every two weeks for cycles 3-6, then every four weeks thereafter in combination with VCd induction.

Yes, Daratumumab and hyaluronidase-fihj (Darzalex Faspro) is FDA approved (2021) for the treatment of Light Chain Amyloidosis.

AL amyloidosis is a rare disease where abnormal plasma cells in the bone marrow make misshapen antibody fragments called light chains. Those light chains misfold, clump together, and deposit in organs (most commonly the heart and kidneys), gradually causing organ failure. It is fatal if untreated and presentation can mimic heart failure or kidney disease.

Dara-VCd is shorthand for daratumumab plus bortezomib (V, also called Velcade), cyclophosphamide (C), and dexamethasone (d). Each component attacks the abnormal plasma cells through a different mechanism, and combining them produces deeper and faster responses than any one alone.

The label specifically advises against use in patients with NYHA class IIIB or class IV cardiac disease, or Mayo stage IIIB, outside of controlled clinical trials. These patients have advanced cardiac involvement and were excluded from the ANDROMEDA trial, so safety and efficacy in that population have not been established.

It contains the same antibody (daratumumab) but adds hyaluronidase, an enzyme that temporarily breaks down a sugar in the tissue under the skin so the antibody can be absorbed there. That allows the drug to be given as a 3-5 minute subcutaneous injection instead of a multi-hour IV infusion, and lowers the rate of infusion-related reactions.

In ANDROMEDA, most hematologic responses occurred within the first 1-3 cycles of treatment. Organ responses (improvements in heart and kidney function) typically lag behind hematologic responses by months because organs need time to clear existing amyloid deposits.