Bispecific Antibody Management in Relapsed Multiple Myeloma

Presentation 

The patient is an 80-year-old male with R-ISS stage I IgG kappa multiple myeloma initially diagnosed with monoclonal gammopathy of undetermined significance (MGUS) in 2005. In 2008, he became symptomatic with worsening anemia and a new L5 lytic lesion. At that time he underwent induction therapy with bortezomib, liposomal doxorubicin, and dexamethasone for about 3 months though further therapy was held due to peripheral neuropathy. He did not want to pursue stem cell mobilization or transplant and 8 months later he progressed with a rise in his paraprotein and free kappa light chain. Imaging at that time was negative. A bone marrow biopsy revealed no high-risk features.  

In 2009, he was initiated on an elotuzumab + lenalidomide phase I clinical trial. He did well for five years and then again progressed. He was then started on a pomalidomide, daratumumab, and dexamethasone clinical trial. He stayed on that trial, eventually discontinuing dexamethasone and then pomalidomide due to side effects.  

He continued monthly daratumumab off-trial for many years with progression in 2024. He had a rise in his M protein and worsening anemia, with restaging PET/CT and a bone marrow biopsy that was unremarkable for new lesions or high-risk features. His other pertinent history includes congestive heart failure (CHF) and hypertension (HTN) with no other health concerns. 

Treatment 

At this point, our patient has been treated for years and is relapsing. His CHF and HTN are well controlled and he remains very active, walking 3–5 miles daily. His neuropathy remains stable and grade 1 with no pain. This progression has been slow, though he lives farther away now and does not want to consider a clinical trial. We spent time discussing current treatment options, including both CAR-T and a bispecific antibody and the risk and benefits of each. When considering chimeric antigen receptor T-cell (CAR-T) therapy vs a bispecific antibody (BsAb), the advanced practice provider (APP) needs to think how the patient is doing clinically and how rapidly the disease is progressing. With this slow progression, we considered CAR-T, although the patient preferred outpatient BsAb treatment. We decided on elranatamab per our institution’s outpatient protocol (table 1) with tocilizumab prophylaxis. Our patient went on to receive elranatamab step-up on Days 1, 4, and 8 and tocilizumab on Day 1 (table 2). He did not experience any cytokine release syndrome (CRS). Home monitoring was performed per table 3.  

The patient continues an antiviral with valacyclovir, was started on Pneumocystis jirovecii pneumonia prophylaxis and monthly intravenous immunoglobulin (IVIG). Day 1 paraprotein was 2.51 g/dL and FKLC was 89 mg/L with stable anemia. He did well with normalization of his FKLC and improvement of both his paraprotein and anemia. His most recent labs show a complete response to therapy. He experienced extreme fatigue, so we eventually took his dosing schedule to every 8 weeks (off-label) with improvement of his fatigue. As mentioned, we started monthly IVIG and our patient has not had issues with recurrent infections at this point.  

Discussion 

Elranatamab is a humanized BsAb that targets both the B-cell maturation antigen (BCMA), which is expressed on the surface of malignant plasma cells, and CD3, which is on the surface of T cells, creating T-cell activation and destruction of the myeloma cell.²BCMA-targeted therapies are approved for myeloma patients who have received immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies, so our patient would be eligible based on his prior treatment history. In the phase 2 MagnetisMM-3 trial, which looked at elranatamab for patients with relapsed or refractory myeloma, patients received weekly subcutaneous elranatamab weekly following step-up dosing.³In this trial, the overall response rate was 61%, with 35% achieving a complete response or greater. Common adverse events included infections (50%), cytokine release syndrome (CRS) (56%-58%), and count issues with neutropenia (15.4%). With a median onset of 2 days, cytokine release syndrome CRS mostly occurs early, during step-up dosing. There was median progression-free survival of 17.2 months with median overall survival of 24.6 months.^2-5Elranatamab has been mainly studied and approved for later-line (≥3–4 prior therapies), heavily pretreated patients. 

When considering a BCMA-targeted therapy for this patient, we had options that included CAR-T therapies and three BsAbs that were approved at the time. APPs have more treatment modalities to consider when discussing next treatment options and they need to consider the clinical status of their patient, prior lines of therapy, and rate of progression when considering BsAb vs CAR-T. There was also an opportunity to have a collaborative discussion with the patient about treatment options and the patient’s preference. This case is an example of a multiply relapsed myeloma patient who has several options and, as APPs, we are an integral part of our care team when discussing and deciding the next line of therapy. 

References 

1. Scott SA, Roberts DL, Gupta VA, et al. Feasibility and Safety of Outpatient Model for Administration of Bispecific Antibodies: Proceedings from an International Myeloma Society 21st Annual Meeting Oral Abstract. Clin Lymphoma Myeloma Leuk. 2025;25(9):656-660. doi:10.1016/j.clml.2025.04.002 
2. Costa LJ, LeBlanc TW, Tesch H, et al. Elranatamab efficacy in MagnetisMM-3 compared with real-world control arms in triple-class refractory multiple myeloma. Future Oncol. 2024;20(17):1175-1189. doi:10.2217/fon-2023-0995 
3. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9 
4. Giles HV, Kishore B. Bispecific Antibodies: Strategies Available to Optimize Their Safe Delivery in Patients with Multiple Myeloma. Antibodies (Basel). 2026;15(1):5. Published 2026 Jan 5. doi:10.3390/antib15010005 
5. Portuguese AJ, Davis JA, Raza S, et al. Real-world outcomes with elranatamab in multiple myeloma: a multicenter analysis from the U.S. Multiple Myeloma Immunotherapy Consortium. Blood Cancer J. 2026;16(1):47. Published 2026 Mar 27. doi:10.1038/s41408-026-01477-z