Smouldering multiple myeloma: It remains unclear whether daratumumab prolongs life

CD38 antibodies such as daratumumab and isatuximab, used as part of combination therapies, have long been part of the standard treatment for active multiple myeloma in the first line of treatment. The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined in an early benefit assessment whether daratumumab also shows advantages over watchful waiting for patients with a precursor of multiple myeloma, also known as smouldering multiple myeloma.

However, the key question for the benefit assessment, i.e. whether this early treatment with daratumumab in the stage of asymptomatic smouldering multiple myeloma improves overall survival in patients, cannot be answered by the AQUILA study presented by the drug manufacturer. Overall, an added benefit of daratumumab is not proven.

Philip Kranz, Head of the Haemato-Oncology and Infectious Diseases Division at IQWiG, explains the problem with the study: “Only about one-third of patients in the comparator group whose disease progressed to active multiple myeloma subsequently received daratumumab or another CD38 antibody as part of a combination therapy. Thus, the remaining two-thirds of the control group received inadequate treatment. That alone could explain the advantage in overall survival observed for daratumumab in the AQUILA study. The manufacturer could have done better – or indeed, should have done better.”

The G‑BA decides on the extent of the added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G‑BA conducts a commenting procedure and makes a decision on the extent of the added benefit.