James A Davis

Background Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are well-documented toxicities of CAR T-cell therapy. To mitigate excessive toxicity, our center has formulated treatment protocols (early vs. standard) for timely management of CRS and ICANS with tocilizumab and/or corticosteroids. Methods This retrospective, single-center analysis included patients treated with CAR T-cell therapy. The goal was to describe the association of two management protocols with toxicity and efficacy outcomes. Results Fifty-five percent of the 40 patients assigned to early management, out of which 5% and 9% developed grade 3+ CRS and ICANS, respectively. Seventy-seven percent and 41% of these patients received tocilizumab and corticosteroids, respectively. Forty-five percent of patients were stratified as standard management, out of which 0% and 11% developed grade 3+ CRS and ICANS, respectively. Seventeen percent and 28% of these patients received tocilizumab and corticosteroids, respectively. The day +90 overall response rate (ORR) for all patients was 63%, with an ORR of 89% for those managed per early management versus 50% for those managed per standard protocol. Conclusion Early use of tocilizumab and corticosteroids is effective in preventing excessive CAR-T-related toxicities with no negative impact on efficacy.

Objective Summarize the background, clinical trials, and place in therapy for the newly Food and Drug Administration (FDA) approved and forthcoming bispecific antibodies for relapsed/refractory (R/R) multiple myeloma. Data Sources A search of the PubMed database was conducted using the following search terms: B-cell maturation antigen (BCMA), teclistamab, myeloma, BsAbs, GPRC5D, and bispecific. Ongoing clinical trials as well as abstracts from ASH and ASCO evaluating the efficacy and safety of novel agents were evaluated. Prescribing information was also reviewed. Summary For patients with R/R multiple myeloma who have failed available therapies, treatment options are limited and survival is short. The FDA recently approved teclistamab, a T-cell-redirecting bispecific antibody, in patients with R/R multiple myeloma who have failed four prior lines of therapy. Teclistamab targets both CD3 expressed on T-cells and BCMA expressed on the surface of myeloma cells, mediating T-cell activation and lysis of plasma cells that express BCMA. Accelerated approval was granted based upon the results of the MajesTEC-1 study, which showed a durable response in a high proportion of heavily pretreated patients. Teclistamab is the first bispecific antibody approved for use in patients with multiple myeloma and the fourth approved agent targeting BCMA. Additional T-cell redirecting bispecific antibodies for use in multiple myeloma are also currently being studied. Conclusion Teclistamab is the newest agent granted FDA approval for use in R/R multiple myeloma and represents a promising new option for patients. Ongoing trials are investigating teclistamab and other novel bispecific antibodies in the upfront and R/R setting.