Dual Antibody Therapy for Extramedullary Myeloma

This week, at the European Hematology Association (EHA) in Milan,  Dr. Shaji Kumar presented the clinical trial results of a new treatment combination for patients with relapsed or refractory multiple myeloma that has spread outside the bone marrow. 

Why Patients with Extramedullary Myeloma Face Greater Challenges

Extramedullary disease (EMD) refers to myeloma cells growing outside the bone marrow in soft tissues. It presents more therapeutic challenges because it responds poorly to standard therapies and often relapses quickly. 

Bispecific antibodies such as talquetamab (Talvey) and teclistamab (Tecvayli) target proteins found on myeloma cells. Both are approved for relapsed or refractory myeloma that no longer responds to standard treatment types. However, as individual therapies, their response rates in patients with EMD have been limited, ranging from 36% to 48%.

Combining Two Antibody Therapies

The RedirecTT-1 phase 2 study tested talquetamab and teclistamab together in 90 patients with relapsed or refractory multiple myeloma and confirmed EMD.

Participants received at least three major classes of prior treatment, with a median of four previous lines. Nearly all treatments (84%) weren’t effective, and some participants had also received advanced therapies such as CAR-T cells or other bispecific antibodies.

Patients received the combination of talquetamab and teclistamab every two weeks, with the option to switch to once every four weeks after several cycles if their disease responded well.

Results show high response rates even after 9 months

The overall response rate (ORR) in this study was 79%, and for those who previously received bispecific antibodies, the ORR was 75%. The patients who underwent CAR-T therapy the ORR was 83%.

The durability of response also stood out, after 9 months, the overall survival was maintained at 80%.

These findings are significant for patients with EMD, a group with limited treatment success using current options. This suggests that combining two antibody therapies may be more effective than using either alone, and may offer benefits comparable to more intensive options like CAR-T therapy.

Side Effects and Safety Considerations

Side effects were common but generally manageable:

• 87% of patients experienced side effects
• The most common side effects included low white blood cell counts (62%) and infections (37%)
• Cytokine release syndrome (CRS), a known side effect of antibody therapies, occurred in 78% of patients but was mostly mild (grade 1 or 2).
• Neurological effects, such as ICANS, occurred in 12% of participants, and only two patients had severe cases.

Changes in taste, skin, and nails were frequent but mild, and most patients received immune support through intravenous immunoglobulin due to reduced antibody levels.

Five patients experienced fatal side effects, including infections such as COVID-19, pneumonia, and sepsis. These highlight the importance of careful monitoring and infection prevention in this population.

What This Means for Patients with Extramedullary Myeloma

This study provides evidence that the dual therapy of talquetamab and teclistamab offers a new treatment option for patients with relapsed or refractory multiple myeloma with extramedullary disease. The combination led to a higher and more durable response rate than what has been seen with either medication alone.

While side effects were common, most were manageable and consistent with previous studies of these therapies. Patients and caregivers should discuss these risks, especially infection-related complications, with their treatment team.

This trial is the largest study focused specifically on patients with extramedullary disease and supports further evaluation of this combination in clinical settings.

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Source: 

• PHASE 2 STUDY OF TALQUETAMAB + TECLISTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND EXTRAMEDULLARY DISEASE: REDIRECTT-1