© Charité | Arne Sattler
The team at Charité – Universitätsmedizin Berlin has observed a remarkable improvement in a female patient with severe systemic lupus erythematosus (SLE) after she was treated with the cancer medication teclistamab. Not long ago, the 23-year-old was confined to a wheelchair due to an autoimmune disease. Nearly six months after beginning the treatment, the patient is now completely symptom-free. It remains to be seen whether this improvement will last over the long term, but the case has been published in the New England Journal of Medicine*, marking a promising starting point for further studies.
Nothing was able to alleviate the symptoms of the 23-year-old patient from Berlin, not even cortisone and eight other therapies meant to control her overactive immune system. Her autoimmune disease, known as systemic lupus erythematosus, was very severe, affecting four of her organ systems. Her skin was blistered, her joints and kidneys were severely inflamed, and her red blood cell count, responsible for supplying oxygen to the body, was too low. “Due to the constant pain she was in, the patient could no longer walk, was confined to a wheelchair, and her kidneys were at risk of failing,” said Dr. Tobias Alexander, the physician treating her at the Department of Rheumatology and Clinical Immunology at Charité. As the Head of the Rheumatology Outpatient Clinic, he had “never seen a case this severe before.”
Because all of the established treatment options had been tried without success, the doctor suggested that the patient should try teclistamab, a bispecific antibody approved for treating multiple myeloma, a type of cancer affecting plasma cells in the bone marrow. In systemic lupus erythematosus, plasma cells produce autoantibodies that target the body’s own tissue. Alexander, a consultant rheumatologist, explained, “Teclistamab is highly effective at destroying the plasma cells and also works against their progenitor cells, which would otherwise rapidly produce new plasma cells. Therefore, we hypothesized that this cancer medication could eliminate the cause of the systemic lupus and provide long-term relief for the patient.”
Disease no longer detectable after five injections
The drug was prescribed “off-label” with the patient’s consent. The treatment took place at the Department of Hematology, Oncology, and Cancer Immunology on Charité Campus Benjamin Franklin and was successful. The patient received five injections of the cancer medication under the abdominal skin over a period of five weeks, which gradually relieved her symptoms. Within a few weeks, her kidney function and blood levels improved, and her skin and joint inflammation completely subsided. Since mid-April, no more autoantibodies have been detected in the 23-year-old’s blood, even though the treatment with immunosuppressants was stopped before the therapy began, and cortisone was no longer administered after six weeks.
“The patient is in full remission,” says Alexander. “This means she is no longer experiencing any symptoms of her disease, and we can no longer find any indication of systemic lupus, either clinically or in the laboratory. It’s too early to say she’s cured, but these powerful results are a rare exception in rheumatology. This is especially remarkable because none of the available treatment approaches had been sufficiently effective before. Most importantly, the success of the therapy signifies a significant improvement in the patient’s quality of life, which we are delighted about. However, we don’t know yet how long the positive effects will last. Since the results are provisional, the therapy is not yet suitable for wider use.”
Risks of the treatment
The drug’s significant impact on the immune system also comes with considerable risks. For instance, immune cells may release excessive amounts of inflammatory mediators. This type of cytokine release syndrome can be life-threatening, depending on its severity. At Charité, a patient undergoing teclistamab therapy experienced severe cytokine release syndrome, along with pneumonia and sinusitis, and a decrease in protective antibodies in her blood. Prof. Jan Krönke, who supervised the patient’s oncological treatment, stated that these side effects are more serious than those seen in traditional rheumatological therapies and sometimes necessitated inpatient care. However, they are consistent with the reactions that teclistamab induces in patients with multiple myeloma and were not unexpected.
The treatment team is closely monitoring the patient and her immune system’s activity to determine how long the positive effects of teclistamab last. If the effects prove to be long-term and are confirmed in further studies, Alexander believes that the cancer medication could have huge potential benefits in rheumatology. Teclistamab’s therapeutic results for the patient are currently comparable with the impact of CAR T-cell therapies. The difference is that the bispecific antibody is much easier to use and can be administered over a shorter period, which would be a considerable advantage. CAR T-cell therapies are new treatment methods that have been able to keep autoimmune diseases at bay for years in individual cases. However, they require chemotherapy and gene therapy, and are very time-consuming and resource-intensive.