Exploring Teclistamab’s Potential in Combination Therapy for Multiple Myeloma: Marc S. Raab, MD, PhD

In an analysis presented at this year’s International Myeloma Society annual meeting, Marc S. Raab, MD, PhD, detailed promising findings on teclistamab (Tecvayli; Janssen Biotech Inc), a first-in-class B-cell maturation antigen x CD3 bispecific antibody, in patients with newly diagnosed multiple myeloma. Specifically that all minimal residual disease (MRD)–eligible patients achieved MRD-negative status at 10–5 and 10–6 thresholds at completion of induction therapy. His interview concludes here with an explanation of why teclistamab is likely so effective when administered in combination and a briefing on other areas and treatment lines in which it is being evaluated.

Raab is a professor of medicine in the Department of Medicine V Hematology, Oncology, and Rheumatology, University Hospital Heidelberg in Germany.

Rewatch part 1 of Raab’s interview, where he discusses the advantages of treatment with teclistamab.

This transcript was lightly edited for clarity; captions were auto-generated.

Transcript

How does teclistamab’s mechanism of action support its use in combination therapy, and what advantages have you observed with this approach?

The mechanism of action, why we need to combine, is many-fold. For a long time, we’ve known that myeloma in general needs to be treated by combination therapies, so shooting from different angles on the same target, meaning the myeloma cell. When we combine immunotherapies that engage T cells, like the bispecifics, we need to make sure first that the T cells can be easily activated and have not any counteracting parts, so to say. Combining teclistamab, in this case, or a bispecific with, for example, a CD38 antibody like daratumumab, can minimize the Treg effect, so minimizing the T cell or counteracting the T-cell activation.

In addition, adding, like in our case, an IMiD [immunomodulatory drug] like lenalidomide, a T-cell–activating agent, that can also, of course, synergistically lead to higher T-cell activity once they are engaged against the myeloma cells and, in addition, work against the myeloma cell, so weakening the myeloma cell itself. Again, at least for the first 2 cycles, adding dexamethasone as we know, is also a potent, short-acting, but potent antimyeloma drug. On the other hand, it has side effects in the long run, so I think it's a good thing that we are able now to limit dexamethasone use for only the 2 first cycles.

In what other disease settings is teclistamab being investigated?

There are many studies, and we're still investigating teclistamab in different disease areas, stages, lines of therapies, in different combinations, either with other bispecifics like talquetamab, or in combination with, as I said, lenalidomide or pomalidomide in later lines, as well in second/third line as well and frontline, but in newly diagnosed patients without transplant eligibility, or at least not planned transplant, or in maintenance settings. All these—some of them are very big phase 3 trials—are ongoing. We will, I think probably see next year, the combination phase 3 clinical trial in 1 to 3 prior lines of therapies, hopefully leading to approval of this kind of combination, and in the longer run, and also in maintenance, and also in a newly diagnosed nontransplant setting in frontline therapy.