A newly published study in Clinical Lymphoma, Myeloma and Leukemia has identified two promising therapeutic targets that could reshape the treatment of multiple myeloma.
Researchers have confirmed that Kappa Myeloma Antigen and Lambda Myeloma Antigen appear on malignant plasma cells but not on healthy ones, opening the door to treatments that could attack cancer cells with far greater precision while sparing the normal immune system.
Multiple myeloma is the second most common form of blood cancer and remains largely incurable, with most patients eventually experiencing relapse after treatment. Current therapies have improved survival in recent years, but many target proteins that are also expressed on healthy immune cells. This can lead to long-term immune suppression and a higher risk of severe infections.
The new research, sponsored by Australian company HaemaLogiX in collaboration with clinical experts from the University of Sydney and the University of Melbourne, demonstrates that Kappa Myeloma Antigen and Lambda Myeloma Antigen may offer a more selective approach.
The study, titled 'Expression of Kappa Myeloma Antigen and Lambda Myeloma Antigen on Malignant but Not Normal Plasma Cells Offers Novel Therapeutic Targets for Patients With Myeloma Amyloidosis and Other Plasma Cell Dyscrasias', provides evidence that the two antigens are consistently expressed on malignant plasma cells across the entire disease spectrum.
Investigators found that the antigens are present from the earliest stages of disease, including the pre-malignant condition known as monoclonal gammopathy of undetermined significance, and become increasingly prominent as myeloma progresses. Their consistent expression and tumour-specific nature make them attractive targets for next-generation immunotherapies, including antibody-based drugs and engineered cell therapies.
Dr Rosanne Dunn, co-founder, executive director and chief scientific officer at HaemaLogiX, said the findings provide strong validation for the company’s strategy to develop therapies that directly target these antigens.
According to Dr Dunn, around seventy per cent of myeloma patients have kappa type disease and are therefore likely to express Kappa Myeloma Antigen, while the remaining thirty per cent with lambda type disease are likely to express Lambda Myeloma Antigen. This distribution creates clear targets for the company’s immunotherapy programs, several of which are already advancing through clinical development.
HaemaLogiX is currently advancing its antibody therapy, KappaMab, which targets the Kappa Myeloma Antigen, in a Phase 2b clinical trial involving patients whose disease has relapsed after treatment with three major classes of myeloma drugs. Earlier clinical studies showed that the antibody did not damage normal immune cells and produced strong responses when used alongside the commonly prescribed myeloma drugs lenalidomide and dexamethasone. The company is also preparing a KMA-targeted CAR T cell therapy for a Phase I trial in patients with relapsed or treatment-resistant disease.
Dr Dunn said the goal is to develop a new generation of treatments that deliver meaningful anti-cancer activity without the immune system damage often associated with existing therapies. She noted that these targeted approaches have the potential to provide effective treatment while reducing side effects and improving patients’ quality of life.
Professor David Gottlieb, a member of HaemaLogiX’s scientific advisory board and the lead author of the paper, described the discovery as an important step forward for patients with multiple myeloma and related plasma cell disorders.
He explained that identifying antigens that appear early in disease and increase as myeloma develops provides strong evidence that they can serve as reliable targets for immunotherapy. Because antigens are selectively expressed on malignant cells rather than on healthy plasma cells, therapies targeting them could treat cancer while preserving much of the patient’s normal immune function. He also noted that standard myeloma drugs, such as lenalidomide, may increase the expression of these antigens, suggesting that combining existing therapies with KMA- and LMA-targeted treatments could yield stronger clinical responses.
The findings arrive at a time when the global multiple myeloma treatment market is dominated by drugs targeting proteins such as BCMA, CD38, and SLAMF7. While these therapies have proven effective, they are not specific to cancer cells and can gradually weaken the immune system through repeated treatment cycles.
Professor Simon Harrison, director of the Centre of Excellence for Cellular Immunotherapy at the Peter MacCallum Cancer Centre and a co-author of the study, said the discovery expands the potential of HaemaLogiX’s technology platform.
He said the ability to selectively attack malignant plasma cells while leaving normal B cells largely untouched represents a significant opportunity to improve treatment outcomes without adding toxicity. For patients with multiple myeloma and other plasma cell dyscrasias, many of whom face a lifetime of repeated therapies and eventual relapse, such advances could provide a much-needed new option.