A team led by Würzburg hematologist Hermann Einsele has defined a new first-line therapy for bone marrow cancer. The antibody “Daratumumab” is being used.
Daratumumab is a therapeutic monoclonal antibody that targets the protein “CD38”, which is found in particular on tumour cells, especially myeloma cells. This means that daratumumab targets tumours directly and at the same time supports the immune system in better recognising and killing cancer cells. This monoclonal antibody has already been approved for the standard treatment of multiple myeloma (or “bone marrow cancer”).
The international phase 3 study “PERSEUS” investigated the efficacy and safety of daratumumab administered subcutaneously in the treatment of patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation. A total of 709 people took part in the study, who were randomly divided into two groups: One group received daratumumab in addition to the standard induction, consolidation (VRd + Daratumumab) and maintenance therapy. The other group only received VRd therapy.
Subcutaneous administration has fewer side effects than intravenous administration
“Subcutaneous administration of daratumumab, that is the injection into the fatty tissue under the skin, is just as effective as intravenous administration and has similar effects on the body. Both forms of administration are safe, but the subcutaneous form has fewer side effects,” explains Prof. Dr Hermann Einsele, Director of the Medical Clinic and Polyclinic II at the University Hospital of Würzburg (UKW), spokesperson for the National Tumour Centre NCT WERA and member of the European Myeloma Network. “It can also be administered more quickly – in just three to five minutes. This means that patients can receive the drug in a single dose, which is convenient and takes less time.”
Enormous progress in the treatment of multiple myeloma
The main focus of the study, which was published in the New England Journal of Medicine, was progression-free survival, that is the time during which the disease could be controlled without progression or death. The results showed that the group that also received daratumumab had a significant advantage in progression-free survival.
In general, enormous progress has been made in the treatment of the disease, says Einsele: 20 years ago, the average survival time for patients was two to three years. In the current study, however, 84.3 % of patients treated with Dara-VRd had survived without progression of the disease after 48 months, compared to 67.7 % in the group without daratumumab.
Other important results were that more study participants in the daratumumab group showed a complete or better response to treatment, and the proportion of patients with a clearance of minimal residual disease was also higher than in the control group. Adverse events, especially severe ones, occurred in both groups, but the addition of daratumumab did not lead to an increased risk of serious side effects.
New first-line therapy for multiple myeloma defined
Hermann Einsele concludes: “Our study shows that the addition of daratumumab to a triple combination therapy in patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation offers a significant advantage in terms of progression-free survival. We have thus defined a new first-line therapy for multiple myeloma. The study is changing practice.
The study was funded by the European Myeloma Network in collaboration with Janssen Research and Development.
Würzburg contribution to immunotherapies for multiple myeloma
Multiple myeloma is the second most common blood cancer after leukemia, in which various malignant tumor foci occur in the bone marrow. The term is derived from the Latin “multiple” for multiple and the Greek “myelos” for marrow. Every year, around 7,000 people are diagnosed with the disease in Germany alone. The risk of developing the disease increases significantly with age.
In patients with multiple myeloma malignant, plasma cells proliferate and grow without control in the bone marrow and thus reduce the production of normal blood cells and displace the healthy white blood cells. Due to this and the reduced production of normal antibodies, infections occur more frequently, the bone structure is destroyed and in some patients renal function is hampered, and those affected suffer from fatigue and loss of appetite. Currently, most patients suffer from disease relapse. However, with a better understanding of the evolution of these malignant bone marrow cells, diagnosis and treatment could be optimized.
Immunotherapies with antibodies or gene-manipulated T-cells, known as CAR-T cells, are seen as a great source of hope. The University Hospital of Würzburg (UKW) plays an important international role in the research, application and further clinical and preclinical development of this new drug principle. Würzburg offers the largest myeloma program in Europe with many clinical studies and accompanying research on the latest forms of therapy such as CAR T-cells and various T-cell activating (bispecific) antibodies.
Publication
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. Pieter Sonneveld, M.D., Ph.D., Meletios A. Dimopoulos, M.D., Mario Boccadoro, M.D., Hang Quach, M.B., B.S., M.D., P. Joy Ho, M.B., B.S., D.Phil., Meral Beksac, M.D., Cyrille Hulin, M.D., Elisabetta Antonioli, M.D., Ph.D., Xavier Leleu, M.D., Ph.D., Silvia Mangiacavalli, M.D., Aurore Perrot, M.D., Ph.D., Michele Cavo, M.D., et al., for the PERSEUS Trial Investigators*. Published in: The New England Journal of Medicine. 12 December 2023. DOI: 10.1056/NEJMoa2312054
