ASCO 2023: A New Bi-Specific Therapy Combination for Relapsed or Refractory Myeloma Patients

If the ASCO 2023 conference reveals a central idea in myeloma research, it's that the treatment options are plentiful.

Many successful therapies have been approved, with many more still in clinical trials. Today, we will highlight one of the clinical trials testing an immunotherapy combination of talquetamab (a bi-specific therapy that has yet to be FDA-approved) and daratumumab (a popular and efficacious therapy for myeloma) for relapsed/refractory myeloma patients.

What question was the clinical trial trying to answer, and what phase was this trial in? 

Can we achieve a synergistic effective outcome in relapsed or refractory myeloma by combining talquetamab and daratumumab? 

Investigators wanted to see if the combination of talquetamab, a bispecific antibody, along with daratumumab, a targeted monoclonal antibody, resulted in a more effective outcome in patients with Relapsed Refractory Multiple myeloma (patients with more than three lines of therapy or were double refractory).

This trial was a Phase 2 study, meaning that the combination of the two drugs had been proven safe for myeloma treatment, but proper dosing levels and efficacy still needed to be assessed. 

How many people participated, and what were the qualifications?

• 65 patients were enrolled. 
• Patients with relapsed refractory myeloma (RRMM)
• 3 or more prior lines of therapy (including a Proteasome inhibitor (PI) and immunomodulatory drug (IMiD) or were double refractory to PI and ImiD)
• The patient had not received anti-CD38 therapy in the last 90 days.

Demographics:

• The median age was 63 years
• 18% of the patients had high-risk cytogenetics
• 25% of the patients had extramedullary plasmacytomas
• The median prior lines of therapy were five

How long did the study last, and when was it completed? 

The official start date of the trial was February 21, 2020. Its estimated completion date is September 9, 2024. For the patients in the trial, the median follow-up was 11.5 months.

What were the preliminary results? 

The Overall Response Rate was 78%, with 66% of the patients achieving Very Good Partial Response (VGPR) or better.

The patients that achieved Complete Response or better were 45%. The median time to first response was one month.

Within a year, 89% of patients who had achieved a Complete Response (CR) still had not progressed. Median Progression-free survival (PFS), a measure to see how long they went without the myeloma progressing, was 19.4 months.

Both drugs without any steroid showed deep and durable responses in patients having already shown no response and even relapsed with other lines of therapy, including anti-CD38/BCMA and CAR-T, suggesting that combined actions of the IMiD can produce solid responses in patients with relapsed/refractory multiple myeloma. 

Why is this important to patients in today's myeloma?

This study shows favorable results in relapsed/refractory myeloma patients that had already tried more than three lines of therapy and failed. Also, many patients often dislike long-term steroid therapy use, and this study showed excellent outcomes without it.
 

We thank the following researchers for making this clinical trial possible, along with the myeloma patients and their caregivers who participated in the trial. 

Bhagirathbhai R. Dholaria, Katja Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Thomas G. Martin, Daniel Morillo, Donna Ellen Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D'Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Kalpana Bakshi, Lijuan Kang, Lien Vandenberk, Marie-Anne Damiette Smit, Niels W.C.J. van de Donk, Ajai Chari, Ralph Wäsch