New immunotherapy for the bone marrow cancer ‘multiple myeloma’

Researchers at Heidelberg University’s Faculty of Medicine and Würzburg University Hospital combined standard treatments in the initial management of patients eligible for stem cell transplantation with a novel immunotherapy: The bispecific antibody teclistamab binds to both immune cells and tumour cells, thereby triggering a targeted immune response. After just a few months, no tumour cells were detectable in the patients, even using the most sensitive methods. The researchers see this as a potential step towards better long-term control of the disease. The results have now been published in the journal *Nature Medicine*.

Thanks to intensive research, treatment outcomes for newly diagnosed multiple myeloma have improved significantly in recent years. Nevertheless, many patients do not achieve complete and lasting control of the disease – known as deep remission – and suffer a relapse. A new immunotherapy could help achieve deep remission more quickly and effectively: In the multicentre German Myeloma Study conducted by the University Medical Centres of Heidelberg (UKHD) and Würzburg (UKW), scientists from both sites investigated the use of the bispecific antibody teclistamab in combination with standard therapy. Teclistamab brings immune cells into close contact with myeloma cells by simultaneously binding to surface structures on both cancer cells and the immune system’s T cells. This activates the T cells, causing them to destroy the myeloma cells.

A total of 49 patients from Heidelberg, Würzburg and nine other German myeloma centres took part in the Phase II trial. All participants were eligible for a stem cell transplant. The primary endpoint – that is, the most important objective of the study – was safety: how well tolerated is teclistamab in combination with the other active substances? In addition, efficacy was investigated: how do patients respond to the treatment?

The bispecific antibody teclistamab complements standard therapy

Patients received Teclistamab in combination with daratumumab, lenalidomide and, in some cases, bortezomib. All three drugs form part of the standard treatment for newly diagnosed multiple myeloma. The antibody daratumumab marks the cancer cells for the immune system; the anti-cancer drug bortezomib disrupts vital metabolic processes in the tumour cells; and lenalidomide activates the immune system and inhibits tumour growth. Several cycles of this combination therapy are usually followed by high-dose chemotherapy and then a transplant of the patient’s own blood stem cells, which were harvested beforehand.

All patients responded to the treatment. In all the bone marrow samples examined by the team after six months, no tumour cells could be detected among one million bone marrow cells. The so-called minimal residual disease (Minimal Residual Disease, MRD), which is measured by the number of remaining myeloma cells per million bone marrow cells, was therefore negative – a finding that, based on numerous international studies, is regarded as a strong predictor of treatment success: Patients who achieve this status generally experience longer disease-free periods and survive longer than those without MRD negativity.

“With very low residual disease following current standard therapy, it is currently assumed that the majority of patients will remain free of disease progression for several years. With MRD negativity, there is good reason to hope for longer-term disease control,” says study leader Professor Marc-Steffen Raab of the Heidelberg Faculty of Medicine at Heidelberg University, Head of the Myeloma Centre at the UKHD and lead author of the publication. “Until now, a negative MRD result has only been achieved in around 65 per cent of patients – and even then only after months or years of treatment. In our study, however, we observed this deep remission as early as the first test after three months and confirmed it using genetic methods after six months.”

From an incurable to a manageable cancer?

“As bone marrow samples were not available for all 49 of our participants at all time points, we can only speak of an MRD negativity rate of over 90 per cent. However, based on the bone marrow samples analysed, 100 per cent are MRD-negative,” said Professor Leo Rasche, senior registrar at the Department of Internal Medicine II at Würzburg University Hospital (UKW) and last author of the study. Although almost all patients developed the side effects expected with standard therapy – including fever, infections and changes in blood counts – these were well managed.

The results must now be confirmed in a randomised Phase III trial, which will be conducted from July 2026 at 60 sites across Germany in a renewed collaboration between the two study groups. “Furthermore, it makes a great deal of sense to clarify whether individual active ingredients in the combination therapy are dispensable or whether the course of treatment can be shortened if patients respond so well to the bispecific antibody after just three months. This would be a huge relief for those affected in terms of their quality of life,” says Leo Rasche.

“These study results could play a key role in finally making multiple myeloma a disease that can be controlled in the long term with the help of modern immunotherapies. In future, we could achieve extremely deep remission in our patients, similar to that seen in Hodgkin’s lymphoma or chronic myeloid leukaemia – that would be an enormous step forward,” adds Dr Niels Weinhold, Privatdozent at Heidelberg University’s Faculty of Medicine and head of a research group at the Heidelberg Myeloma Centre.

The study is the first report from a German myeloma trial in which the UKHD and the UKW have merged their two multiple myeloma study groups: the German Multiple Myeloma Study Group (DSMM), based in Würzburg, and the German-Speaking Myeloma Multicentre Group (GMMG), based in Heidelberg. “Together, we are simply stronger,” says Leo Rasche, who spearheaded the study in Würzburg alongside Professor Hermann Einsele (Director of the Department of Internal Medicine II and Head of the DSMM) and Professor Martin Kortüm (Head of Translational Myeloma Research).

Publication

Marc S. Raab, Niels Weinhold, K. Martin Kortüm, Jan Krönke, Roland Fenk, Katja Weisel, Lilli Podola, Uta Bertsch, Alexander Brobeil, Julia Mersi, Stefanie Huhn, Ryan Arlinghaus, Michael Hundemer, Stephan R. Bohl, Elias K. Mai, Natalie Schub, Johannes Waldschmidt, Florian Bassermann, Carsten Müller-Tidow, Christoph Heuck, Caline Sakabedoyan, Josephine Khan, Elena Ershova, Bas D. Koster, Monika Engelhardt, Mathias Hänel, Hans Salwender, Raphael Teipel, Hartmut Goldschmidt, Hermann Einsele, Leo Rasche, on behalf of the GMMG-HD10/DSMM-XX (MajesTEC-5) investigators. Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04471-x