Oncology Clinical Pharmacy Specialist Winship Cancer Institute, Emory University TUCKER, Georgia, United States
Introduction: Teclistamab (Tecvayli®), elranatamab (Elrexfio™), and taqluetamab (Talvey™) are T-cell redirecting bispecific antibodies (BsAbs) that gained accelerated approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have been treated with 4 prior lines of therapy (LOT) by FDA and with 3 prior LOT by EMA. All 3 BsAbs have a REMS program due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The package inserts support hospitalization to receive the initial step-up doses for CRS and ICANS monitoring. In an effort to transition administration of BsAbs to outpatient (OP) setting, thereby minimizing hospitalization and reimbursement burdens, we implemented an institutional protocol to deliver step-up and target doses in the OP setting.
Methods: Eligible patients must stay within 30 minutes of the Immediate Care Center (ICC) and have a 24-hour caretaker until 48 hours after the receipt of the target dose of the BsAb. Patients did not qualify for OP step-up dosing if they had known significant disease burden, circulating plasma cells, prior history of CRS or ICANS or poor performance status. Step-up doses were administered on days 1, 4 and 8 of the step-up dose cycle preceded by acetaminophen, diphenhydramine, and dexamethasone before each dose. All patients received prophylactic tocilizumab prior to dose #2 per institutional protocol. From initiation of step-up dose #1 until 48-hours after the target dose, patients monitored temperature every 8 hours or in the setting of new CRS symptoms, and for signs of ICANS. If fever or neurologic change occurred, patients took dexamethasone 20 mg, diphenhydramine 50 mg and acetaminophen 650 mg and were instructed to present to the ICC for toxicity assessment and management.
Results: From 9/1/2023 to 3/31/2024, 41 patients received OP BsAb step-up dosing. During the same time, 42 patients received inpatient BsAb. The median age for OP BsAb was 62 years (range, 38-81), 54% were male, 44% were African American, and patients had received a median of 4 prior LOT (range, 3-9). Overall, 6 patients (15%) experienced CRS (four grade 1, one grade 2 and one grade 3) and 1 patient (2%) experienced ICANS (grade 1). Three patients (7%) required hospitalization for toxicity management (1 for grade 3 CRS and grade 1 ICANS, 1 for grade 2 CRS, and 1 for grade 1 CRS). The median time of hospitalization was 7 days (range, 6-15). The other 3 patients were treated with tocilizumab in the ICC and discharged home with symptom resolution. All patients recovered from CRS and ICANS without additional toxicity.
Conclusions: Implementation of this OP protocol to administer BsAbs is feasible and minimized the risk of CRS, ICANS and hospitalizations for step-up dosing. The low incidence of CRS (14%) and ICANS (3%) with prophylactic tocilizumab and premeds and the low hospitalization rates make this appealing for selected RRMM patients and likely can be adopted to larger practices.