This is a study with the combination of two bispecific antibodies, teclistamab and talquetamab, for the treatment of relapsed/refractory myeloma. Actually, this is the first time two bispecific antibodies have been combined to treat a haem malignancy so it’s really exciting.

What was the study design?

This is a phase Ib trial and we had an extensive dose escalation employed to reach the recommended phase II dose, RP2R. So each dose level employed step-up dosing as well to mitigate the toxicity and we ended up with the final dose of teclistamab at 3mg/kg and talquetamab at 0.8mg/kg.

What did you find?

The primary objective of the study was to look at safety, of course, being a phase Ib. Indeed, it was very reassuring to confirm that the combination’s safety profile was manageable and toxicities were comparable to that of the monotherapies of teclistamab and talquetamab given as separate medications. 

The CRS rate was also similar to the monotherapies and most of the CRS events were grade 1 and 2 and could be really controlled easily. About a quarter of the patients got tocilizumab to control the CRS and they occurred mostly during the step-up dosing and during the first cycle. 

Infections occurred in about 80% of the patients but less than 40% actually had a grade 3-4 AE. The most common infections were COVID-19 and pneumonia and upper respiratory tract infections. There were six deaths due to infection on the trial. But, overall, the safety was really manageable and that it can be expected in this really tough to treat patient population. 

So there were 93 patients included on the study with four prior lines of therapy. The median age was 65 and there was a large proportion, about a third of the patients, who had extramedullary disease. This is a really tough kind of myeloma to treat. Also about a quarter had prior BCMA exposure and 90% were refractory to their last line of therapy. So really a very refractory kind of patient. 

The efficacy result had an overall response of 86% in the entire cohort and in the RP2R it was up to 96%. This was over a follow-up of 14 months for the entire cohort. So this was really very encouraging. At the data cut-off, actually, over 60% of the patients remained on study. The responses were rapid, they occurred within two months, and they deepened over time. Actually the duration of response at RP2R was not reached, was not estimable.

How could this research impact the future treatment of relapsed/refractory multiple myeloma?

These results are really encouraging because this is the first time such a combination of bispecifics is studied. One of the most interesting populations this might impact is those patients with extramedullary disease. So we know this is a really tough patient population to treat and in other studies the response rates varied between 5-40%. Here, in these extramedullary disease patients, we had 85% response in the RP2R. So this is a big message for these tough patients. Indeed, there is already an expansion cohort that is planned for extramedullary disease.

I think these encouraging results will lead to further investigation of this combination in various settings of myeloma patients. As we always do in the myeloma field, we start with advanced patients and then when we have success we move up front. So perhaps this will also happen.

Anything to add?

I want to say that the durability of the responses is quite amazing. Patients are just living on and on. These are patients I would have expected to have lost without this study so it’s really a great sense to be part of this. So it’s really a privilege and it’s great news for the patients.