Limited-duration bispecific antibody therapy for multiple myeloma
Alfred Garfall
MDPerelman School of Medicine at the University of Pennsylvania
Project Term: July 1, 2024 - June 30, 2027
Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Most bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Preliminary results suggest that patients with good responses may be able to stop therapy and enjoy a period of time off-therapy with close observation, which may limit long term toxicities caused by continuous therapy. We propose a clinical trial to test this limited-duration approach with recently approved bispecific antibodies for multiple myeloma.
Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Long-term bispecific antibody therapy has been linked to certain risks, especially infection. Because bispecific antibodies are so effective at controlling multiple myeloma, it is possible that bispecific antibodies could be stopped once patients have achieved a good response. After stopping, patients could be monitored closely and resume the bispecific antibody if the multiple myeloma starts growing again. The potential benefits of this approach include a treatment-free period for patients and less long-term toxicity. However, it is uncertain whether this approach is equally effective for multiple myeloma control compared to the traditional continuous approach. The clinical trial we propose will preliminarily evaluate limited-duration bispecific antibody therapy for multiple myeloma patients.
Our clinical trial will first focus on patients who have been receiving the first FDA-approved bispecific antibody for multiple myeloma, teclistamab. Patients who have been receiving teclistamab for 6-9 months and who have achieved a good response will be offered enrollment. Patients who enroll will discontinue teclistamab and undertake monthly monitoring for disease progression. At the first sign of multiple myeloma growth, patients will resume teclistamab. The main outcome the study will assess is how many patients experience multiple myeloma growth within six months of stopping teclistamab. In patients who experience multiple myeloma growth, we will assess whether resuming teclistamab controls that growth.
The portion of the clinical trial focusing on teclistamab patients has already begun. We aim to expand this study and additionally study patients receiving a newer bispecific antibody called talquetamab.
We would also like to develop testing of patients’ immune system that could predict which patients can stop therapy and which patients would be better-off continuing therapy without interruption. A challenge is that immune system tests performed in the research laboratory are often too complicated to be performed and interpreted in the clinic. To address this challenge, we are taking advantage of an initiative in our university called the “Immune Health Project.” The goal of the Immune Health Project is to make sophisticated immune system testing available in the clinic. In this clinical trial, we will preliminarily evaluate whether an immune system test that could be made available in the clinic through the Immune Health Project can identify patients at risk for early multiple myeloma growth after stopping bispecific antibody therapy.