Relapsed Multiple Myeloma Treated with Teclistamab

History of Present Illness

JD is a 68-year-old male who was initially diagnosed with multiple myeloma in 2019 following an evaluation for progressive fatigue, back pain, and incidental finding of anemia during a routine checkup. At initial diagnosis, laboratory studies revealed an elevated serum total protein (10.2 g/dL), a decreased albumin/globulin ratio (0.4), and an M-spike of 3.2 g/dL identified as IgG kappa on immunofixation. A serum-free light chain assay showed elevated kappa free light chains (220 mg/L) with an abnormal kappa/lambda ratio of 18:1. Beta-2 microglobulin was elevated at 5.8 mg/L. A bone marrow biopsy demonstrated 40% clonal plasma cells, and fluorescence in situ hybridization revealed standard-risk cytogenetics with no high-risk abnormalities. A whole-body low-dose CT scan showed multiple lytic lesions in the lumbar spine and pelvis. Based on these findings, JD was diagnosed with IgG kappa multiple myeloma, Stage II per Revised International Staging System.

JD received induction therapy with lenalidomide, bortezomib, and dexamethasone (RVd) for 4 cycles, achieving a very good partial response (VGPR). He then underwent autologous stem cell transplantation followed by maintenance therapy with lenalidomide at 10 mg daily. He achieved a complete response (CR) 8 months after transplant and remained on maintenance therapy for 24 months with good tolerance. Due to a rising M-spike level from undetectable to 0.8 g/dL over 2 consecutive months, JD received daratumumab, pomalidomide, and dexamethasone (DPd) for management of his first relapse for a total of 12 months. He achieved a partial response but experienced disease progression as evidenced by rising M-protein levels (2.3 g/dL), worsening anemia (hemoglobin 8.9 g/dL), and new-onset renal impairment (creatinine 1.8 mg/dL). A repeat bone marrow biopsy showed 35% plasma cells.

Impression

At this point, JD had received therapy with an immunomodulatory agent (lenalidomide, pomalidomide), a proteasome inhibitor (bortezomib), and an anti-CD38 monoclonal antibody (daratumumab), and was considered to have triple-class–exposed relapsed multiple myeloma.

Plan

For management of his second relapse, JD was then offered participation in MajesTEC-9, a clinical trial designed to randomize patients to teclistamab vs. standard of care for patients exposed to an anti-CD38 monoclonal antibody and lenalidomide and who have received 1-3 prior lines of therapy. He was randomized to teclistamab, which was administered according to the recommended dosing schedule¹:

Step-up dose 1: 0.06 mg/kg SC (day 1)

Step-up dose 2: 0.3 mg/kg SC (day 4)

First full dose: 1.5 mg/kg SC (day 7)

Subsequent maintenance doses: 1.5 mg/kg SC weekly

JD was hospitalized for the first three doses to monitor for cytokine release syndrome (CRS) and other early adverse events. Premedication included acetaminophen, an H1 blocker, and dexamethasone prior to each step-up dose.

As for tolerability, JD experienced Grade 1 CRS after the first full dose (day 7), manifesting as fever (38.5°C), chills, and mild hypotension. This resolved within 24 hours with supportive care and a single dose of tocilizumab. Grade 3 neutropenia (ANC 500-1000/μL) occurred during week 3 of treatment, requiring a dose delay of one week. He also experienced grade 2 thrombocytopenia (platelets 50,000-75,000/μL) and persistent grade 1 anemia. He developed a grade 2 upper respiratory tract infection during month 2 of treatment, which resolved with oral antibiotics.

After 4 weeks of therapy, JD showed initial signs of response with a 50% reduction in serum M-protein levels (from 2.3 to 1.15 g/dL). By the 12-month assessment, he had achieved a stringent complete response with no detectable M-protein by immunofixation and normalized free light chain ratio.

Discussion

Based on JD’s triple-class–exposed status and disease characteristics, teclistamab on trial (MajesTEC-9) was selected as his third line of therapy.² Teclistamab is a B-cell maturation antigen (BCMA) x CD3 bispecific antibody that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. Currently, teclistamab is approved for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal

antibody. The MajesTEC-9 trial is designed to understand the safety and efficacy of teclistamab in comparison to standard of care therapies such as pomalidomide, bortezomib, dexamethasone or carfilzomib, and dexamethasone in early relapse (1-3 prior lines).

Teclistamab has shown high response rates and durable remissions in triple-class–exposed patients with relapsed/refractory multiple myeloma. A retrospective real-world study evaluating the efficacy and safety of teclistamab treated at 9 academic centers from 5 countries demonstrated that, with a median follow-up of 5.3 months, the overall response rate was 67%, including 55% with a VGPR or better. The 6-month progression-free survival and overall survival rates were 53% (95% CI [confidence interval], 46–61%) and 73% (67–80%), respectively. CRS occurred in 54% of patients, and infections were reported in 56.2% of patients, with 22% having grade ≥3 infections.³

The key to success with novel agents such as bispecifics is appropriate mitigation and management of side effects. It is prudent to ensure the patient is up to date on all vaccinations, screened for hepatitis B, C, and HIV, given prophylaxis for Pneumocystis jirovecii pneumonia and herpes viruses, and that their immunoglobulin levels are monitored regularly with administration of IgG replacement if levels fall below 400 mg/dL.

For JD, CRS was managed with tocilizumab and supportive care. Subsequent doses were administered in the outpatient setting with close monitoring. Neutropenia required a 1-week treatment delay and resolved to grade 1 without growth factor support. Subsequent doses were administered at full dose with no recurrence of grade 3 neutropenia. Infections were managed with appropriate antimicrobial therapy and IVIG supplementation to manage hypogammaglobulinemia. Prophylactic measures were maintained throughout treatment.

References

1. Janssen Biotech, Inc. (2024). Tecvayli (teclistamab-cqyv) package insert. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf

2. Cyrille Touzeau et al. MajesTEC-9: A randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 41, TPS8067-TPS8067 (2023).

https://doi.org/10.1200/JCO.2023.41.16_suppl.TPS8067

3. Tan, C.R., Asoori, S., Huang, C.Y., et al. Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): An International Myeloma Working Group Study. Blood Cancer J. 15, 53 (2025). https://doi.org/10.1038/s41408-025-01259-z