The use of novel immunotherapeutics in multiple myeloma (MM) treatment has grown exponentially in the last three years. This has largely been driven by the approval of bispecific T-cell engaging antibodies (BsAbs). Bispecific antibodies are drugs that simultaneously bind to a multiple myeloma cell surface antigen and T-cell marker, CD3, to bring them in proximity of each other leading to activation of the T cell and killing of the myeloma cell. Current BsAbs available under the FDA-accelerated approval program include teclistamab (Tecvayli®); talquetamab (Talvey®) and elranatamab (Elrexfio®) based on registrational studies; MajesTEC-1; MonumenTAL-1; and MagnestisMM-3, respectively. Tecvayli and Elrexfio are both B-cell maturation antigen (BCMA-) binding BsAbs, while Talvey targets G protein–coupled receptor class C group 5 member D (GPRC5D). These medications are highly effective as single-agent therapies in relapsed/refractory MM, in which patients are triple-class exposed and have received at least four prior lines of therapy.
Since their FDA approvals in October 2022 and August 2023, the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute has safely treated over 200 patients with BsAbs for relapsed/refractory MM. Even though most of the patients treated would not have been considered eligible for the clinical trials that led to the approval of these medications, due either to the nature of their disease or medical co-morbidities, we have seen outcomes comparable to those seen on the registrational trials. The vast majority of patients tolerate therapy well with reassuring safety metrics; high-grade cytokine release syndrome (CRS) events or immune cell associated neurotoxicity (ICANS) with step-up dosing (<1%) have rarely been seen.
Given the success of our ambulatory stem cell transplant and cellular therapy programs, as well as similarities in toxicity profile with immune cellular therapies such as chimeric antigen receptor T-cell (CAR-T) therapy, we launched the bispecific outpatient safe step-up (BOSS) program in March 2024. This program allows patients that live or are temporarily staying within one hour of Dana-Farber's Longwood Campus that are deemed eligible by their treatment team to complete the step-up-dosing for these therapies in the ambulatory setting. Patients are seen in clinic daily and closely followed by our clinician, pharmacist, and nursing teams. Similar to the ambulatory transplant and cellular therapy programs, this program has been a success, with over four days of hospitalization saved per patient on average from what is typically a 7-9-day hospitalization. Some patients have been able to avoid hospitalization altogether. In addition, in the event of toxicities, we have been able to ensure rapid admission and delivery of appropriate medical therapy to patients who have developed the common CRS or other side effects of BsAbs therapy.
Given the promising results of BsAbs in multiple myeloma treatment, we have been and continue to enroll patients to clinical trials evaluating these therapies. Currently available clinical trials with BsAbs include those treating precursor or early disease and relapsed/refractory MM, either as single agent therapies or in novel combinations. In addition, some clinical trials with BsAbs also include limited step-up dosing or step-up dosing in the outpatient setting, further improving our ability to offer next-generation immune therapies to our patients without the need for a prolonged hospital stay.
Research Studies
Currently available clinical trials:
- 22-154: Immuno-PRISM: Immunotherapies for high-risk smoldering multiple myeloma
- 24-135: LINKER-MGUS1: Linvoseltamab in patients with high-risk monoclonal gammopathy of undetermined significance or non-high-risk smoldering multiple myeloma
- 23-585: Phase 2 ABBV-383 combination for patients with relapsed/refractory multiple myeloma
- 23:402: Elranatamab as consolidation after idecabtagene vicleucel in relapsed refractory multiple myeloma
Upcoming clinical trials:
