Nursing Considerations for Teclistamab/SC Daratumumab’s Approval in Second-Line MM

On March 5, the FDA approved the combination of teclistamab (Tecvayli) and daratumumab hyaluronidase-fihj (Darzalex Faspro) for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy. This approval, processed through the Commissioner’s National Priority Review Voucher (CNPV) pilot program, also converted the accelerated approval of teclistamab monotherapy into a standard approval.

The efficacy of this combination was established in the phase 3 MajesTEC-3 trial (NCT05083169), which demonstrated a 56% reduction in the risk of death compared to investigator’s choice control groups. Samantha Shenoy, MSN, NP, an oncology nurse practitioner at UCSF, shared insights with Oncology Nursing News on the clinical implications of this approval and the critical role of advanced practice providers (APPs) and oncology nurses in managing these patients.

Oncology Nursing News: What is the significance of moving the teclistamab and daratumumab hyaluronidase combination into the second-line setting?

Shenoy: MajesTEC-3 evaluated the combination of teclistamab and daratumumab hyaluronidase. Teclistamab is a bispecific antibody that targets BCMA, and subcutaneous daratumumab is a monoclonal antibody that targets CD38. Data on the final results of MajesTEC-3 were presented at the 2025 American Society of Hematology [ASH] Annual Conference. The combination was FDA approved this week.

This is a very exciting development because this combination of teclistamab and daratumumab hyaluronidase is [approved] in the second line. In multiple myeloma, we want to give the best therapies we can upfront because over time, we see attrition; therapies given later in the disease course often do not have the same durability as those given upfront.

What are the primary safety considerations and adverse effects that nurses and APPs should prioritize?

Teclistamab is a bispecific antibody that targets BCMA on the surface of normal and malignant plasma cells as well as mature B cells. [Data presented at the 2025 ASH Annual Meeting showed that] these patients have profound hypogammaglobulinemia.

It’s very important for APPs and nurses to know that when patients are receiving teclistamab, whether it’s monotherapy or with daratumumab hyaluronidase, patients must be on the appropriate infection prophylaxis. Subcutaneous daratumumab can also contribute [to low blood counts and an increased risk of infection].

What specific infection prophylaxis protocols do you recommend for patients starting this regimen?

[Prophylaxis] should include VZV/HSV prophylaxis valacyclovir [Valtrex] or acyclovir and PJP prophylaxis sulfamethoxazole/trimethoprim [Septra] or equivalent. At UCSF, once the immediate risk for CRS has passed, we start patients on monthly intravenous immunoglobulin (IVIG). Research published in 2025 by Rahul Banerjee, MD, FACP, and colleagues highlights that IVIG can reduce infection rates by approximately 90% in these patients. We’ve implemented this at UCSF because we know there’s a significant reduction in infections.

Does the need for monitoring and prophylaxis change once a patient stops treatment?

The other important piece for APPs and nurses to know is that even when the patient has stopped receiving the drug, it’s important to continue the IVIG and the prophylaxis. For IVIG we continue it anywhere from 6 months to 1 year or longer because…humoral immunity generally does not start until around the 6-month mark.

Plasma-cell recovery doesn’t start until 6 months later, even after stopping the drug. Just because a patient is no longer on the drug, don’t forget that you need to be on high alert for infections; don’t stop the prophylactic measures. We also keep people on PJP prophylaxis for 6 months after and check CD4 counts at that time.

This transcript has been edited for clarity and conciseness.

Reference

FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. FDA. March 5, 2026. Accessed March 5, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple