ASH23: CAR-T therapy shows early promise in autoimmune diseases
11 Dec 2023
Clinical ResultCell TherapyASHImmunotherapy
Preliminary results from an early-stage study presented at the American Society of Hematology (ASH) meeting provided some of the first clinical evidence supporting the use of CAR T-cell therapies to treat autoimmune diseases. "We have opened up an entirely new route of possibly treating several more diseases," remarked lead author Fabian Müller.
The trial initially focused on patients with systemic lupus erythematosus (SLE) who were treated with a single infusion of CD19 CAR-T cells. After promising results in the first five patients with SLE, the study was expanded to also include people with two other autoimmune diseases that involve autoreactive B-cells: systemic sclerosis (SSc) and inflammatory myositis (IIM).
Results after a median of 15 months of follow-up showed that in all 15 patients treated with CD19 CAR-T cells, CD19+ B-cells were eliminated from the blood after around 5.9 days. Researchers noted that B-cells reoccurred in 12 of the patients a few months later, although the three most recently treated subjects are still B-cell aplastic. Despite this, all 15 patients entirely stopped immunosuppressive drugs.
‘Life-changing’ results
Further data showed that all eight SLE patients reached complete remission after 3 months and maintained an SEL Disease Activity Index (SLEDAI) of zero. Meanwhile, the five SLE participants with follow-up of at least 14 months stayed in remission despite reconstitution of B-cells. "The results have really been life-changing for these patients,” Müller said.
For IIM, the researchers noted that all three patients experienced major improvement and normalisation of creatine kinase after 3 months, which is ongoing. Meanwhile, in the four patients with SSc, three with follow-up >3 months showed a decreased disease activity as measured by EULAR AI of -4.3. "The disease is entirely controlled without any additional disease-related therapeutics so far," said Müller
In the study, 10 patients experienced mild cytokine-release syndrome (CRS), while there was one case of Grade 2 CRS and once case of immune-effector cell associated neurotoxicity syndrome that presented as vertigo two weeks after infusion with the CD19 CAR-T cell therapy. "We are hopeful that this is at least as good as autologous bone marrow transplant with substantially fewer side effects, but the data are preliminary, and we need to do follow up studies to confirm these results,” Müller commented.
Shadow of FDA probe
A number of companies are looking to translate the success of CAR-T therapies in oncology across to immunology, including Novartis. At the drugmaker’s recent R&D day, it highlighted provisional data in SLE, along with Sjögren’s syndrome and severe rheumatoid arthritis. However, the disclosure was overshadowed by the launch of an FDA probe into a serious risk of T-cell malignancies with the handful of CAR-T therapies currently on the market, including Novartis’ Kymriah (tisagenlecleucel).
While the investigation is in its early stages, Angelika Jahreis, Novartis’ immunology head, said the company’s understanding is that the risk of developing haematologic malignancies associated with real-world use of CD19- or BCMA-targeting CAR-T’s is “extraordinarily low.” FirstWord is also in the process of gaining key opinion leader feedback on the FDA’s probe.
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