Early Data Show Fast, Deep Responses With Teclistamab-Based Regimen for Multiple Myeloma

Insights From the 64th American Society of Hematology Annual Meeting & Exposition

Emma Searle, MD, PhD, reviews early data from MajesTEC-2, a trial designed to evaluate the recently approved monoclonal antibody teclistamab in combination with daratumumab and lenalidomide in patients  with relapsed/refractory multiple myeloma.

What inspired your research into teclistamab’s efficacy in combination with daratumumab and lenalidomide?

MajesTEC-1 was the monotherapy study of teclistamab that led to its approval by the US Food and Drug Administration. In MajesTEC-1, teclistamab monotherapy had a very high response rate of 63% in patients with relapsed/refractory multiple myeloma. This begged the question of whether we could do better by treating patients in combination with other known, standard care myeloma drugs in an earlier line of therapy. In MajesTEC-2, we examined the combination of teclistamab with daratumumab and lenalidomide.

Thank you, Dr Searle. Can you review the specific patient population you worked with, as well as your findings?

This was a non-randomized, phase 1b trial. The median number of prior lines of therapy was 2. All the patients were already treated with a proteasome inhibitor and an immunomodulatory drug (IMiD) in previous lines of therapy. About 20% of patients were IMiD-refractory, and one-third of patients were daratumumab-refractory going into this trial, but these did not exclude participants. 

There were 2 different dosing cohorts. We started off dosing with 0.17 mg/kg, then moved to 1.5 mg/kg of teclistamab weekly. Then, patients receiving 1.5 mg/kg moved to administration every other week in the third cycle, which is obviously popular with patients who would prefer to come to the hospital less.

The more mature data is from the cohort at the 0.72 mg/kg dosing level, where we saw an overall response rate of 100% with a median follow-up of 11 months. The less mature data is from the cohort receiving 1.5 mg/kg. Overall response rate in this cohort was still very high at 90% with a median follow-up of 6 months. Responses are quick, with a median of 1 cycle of therapy to first response and 3 cycles to complete response or better. The complete response rate across the 2 dosing cohorts is 55%. Certainly, this combination of therapies has the potential to induce rapid and deep responses.

In terms of the side effect profile, we did not see anything we were not expecting. With daratumumab, lenalidomide, and teclistamab, cytokine release syndrome is very common but appears to be manageable. The only cytokine release syndrome events were grade 1 and 2 and occurred during cycle 1. 

About 40% of patients received tocilizumab and other supportive care measures, such as steroids or anakinra. The most common hematological adverse event was neutropenia, which was very common, but febrile neutropenia occurred infrequently. There were only 4 cases of febrile neutropenia across the 2 dosing cohorts. 

The other important side effect to mention is infection. Ninety percent of patients experienced an infection of some type during the study. Most of those infections were, fortunately, of low grade, with common infections including COVID-19, respiratory tract infections, and pneumonia. Sadly, we did lose 2 patients in this study to infection: one with COVID-19 and one with sepsis. An important message for practitioners treating patients with multiple myeloma is to be vigilant for infection, particularly in these very potent combination therapy studies.

It might be too early to say, but how do you predict your findings will inform future care and research?

While I think it is too early to comment on durability, and the median duration of response had not been reached at the point of data cut-off for my presentation, it is fascinating to see responses deepening over time. 

We would like to know what response rates and side effect profile we would see using teclistamab in the first line and in a prospective trial comparing it to a standard of care. That is planned for MajesTEC-7, where lenalidomide, daratumumab, and dexamethasone will be compared to lenalidomide, daratumumab, and teclistamab. MajesTEC-7 will be conducted with transplant-ineligible patients, or patients for whom hematopoietic stem cell transplant is not planned as part of their first line of therapy. It will be interesting to see how the novel, immune-based tripletive of teclistamab, daratumumab, and lenalidomide fares in a head-to-head comparison. 

Is there anything else you would like to add?

As always, I want to thank the patients who have participated in this study. Research is a collaboration with our patients, and we could not do it without them.