Subcutaneous daratumumab is a targeted therapy used in the treatment of multiple myeloma, a cancer affecting plasma cells in the bone marrow. This medication, known by its brand name Darzalex Faspro, represents a specific method of delivering the drug daratumumab. The term “subcutaneous” signifies that the treatment is administered via an injection into the fatty tissue just beneath the skin. This form of daratumumab is used for both newly diagnosed individuals and for those whose cancer has returned after other therapies, providing an alternative to the original intravenous (IV) method.
Mechanism of Subcutaneous Daratumumab
Daratumumab’s effectiveness stems from its function as a monoclonal antibody, a type of protein engineered to recognize and attach to a specific target. The target is a protein called CD38, which is found in high numbers on the surface of multiple myeloma cells. When daratumumab binds to CD38, it “tags” the cancerous plasma cells, signaling the patient’s own immune system to find and destroy them.
The subcutaneous version of this therapy includes an additional component: an enzyme called recombinant human hyaluronidase PH20. Under normal conditions, the subcutaneous space contains a gel-like substance called hyaluronan, which limits how much fluid can be injected at one time. The hyaluronidase enzyme works by temporarily and locally breaking down this substance.
This enzymatic action creates a temporary space, allowing a larger volume of daratumumab to be delivered in a single injection. The breakdown of hyaluronan is reversible, and the area under the skin returns to its normal state within a day or two. This co-formulation enables the drug to be absorbed into the bloodstream, where it can circulate to target the multiple myeloma cells.
The Administration Process
Receiving subcutaneous daratumumab is a markedly different experience for patients compared to its intravenous counterpart because the process is significantly shorter. A healthcare professional gives the injection into the subcutaneous tissue of the abdomen, a procedure that takes only about three to five minutes to complete. This stands in stark contrast to the intravenous infusion of daratumumab, which can require several hours per session.
Before the injection, patients receive a set of premedications. These often include a corticosteroid, an antihistamine, and a medication to reduce fever, such as acetaminophen. This preparatory step is taken to minimize the risk of administration-related reactions, which are potential responses the body can have to the treatment.
Following the injection, patients are monitored by the clinical staff for a period of time. This observation period is particularly important during the first few treatment cycles to ensure any immediate reactions can be managed promptly.
Efficacy Compared to Intravenous Infusion
For subcutaneous daratumumab, clinical trials were designed to directly compare its effectiveness to the established intravenous (IV) infusion. The Phase III COLUMBA study demonstrated that the subcutaneous formulation was “non-inferior” to the IV version. In clinical trial terms, non-inferiority means that the new treatment is not unacceptably worse than the existing one.
The COLUMBA study showed that the overall response rates and the progression-free survival rates were very similar between patients receiving the subcutaneous injection and those receiving the IV infusion. This finding was important, as it confirmed that the convenience of a quick injection did not compromise the drug’s ability to control multiple myeloma.
The results from this and other studies, such as the PERSEUS and CEPHEUS trials, have established that patients can expect similar clinical outcomes from either delivery method. The consistent results across these studies provide confidence that the subcutaneous route is a reliable and effective alternative.
Potential Side Effects and Management
The most common side effect is an injection site reaction. These reactions occur at the spot where the drug was injected, typically the abdomen, and may include symptoms like redness, swelling, bruising, or itching. These localized effects are generally mild and tend to decrease in frequency after the first few doses.
Patients may experience other side effects common to both forms of daratumumab. These can include fatigue, nausea, diarrhea, constipation, and an increased risk of upper respiratory tract infections. A reduction in blood cell counts, such as neutropenia (low white blood cells) or anemia (low red blood cells), is also possible and is monitored through routine blood tests.
Systemic administration-related reactions, which affect the whole body, can also occur and may manifest as chills, fever, or shortness of breath. However, these types of reactions are much less common and typically less severe with the subcutaneous injection compared to the IV infusion. Patients should report any side effects to their healthcare team for guidance on management.