Associate Professor Loyola University Chicago Elmhurst, Illinois, United States
Introduction: Targeting B-cell maturation antigen (BCMA) has changed treatment approaches in relapsed refractory myeloma (RRMM). Teclistamab is a bi-specific antibody that targets CD3 expressed on T cells and BCMA expressed on myeloma cells. Recently FDA approved based on the MajesTEC-1 trial which excluded patients with a CrCl < 40 mL/min, there is a need to better understand safety and efficacy of RRMM with chronic kidney disease (CKD) seen in up to 50% of RRMM patients as well as those with end stage renal disease (ESRD). Other therapies have been shown to be safe and effective in ESRD patients but there are no reports of teclistamab in this patient population.
Methods: This was a retrospective study evaluating patients with RRMM with ESRD treated with teclistimab since FDA approval at our institution.
Results: We report here our experience with two RRMM patients with ESRD who received Teclistamab. The first patient was a 63 year old male with IgG-Lambda MM and R-ISS stage II disease at diagnosis. Prior to treatment, his lambda light chain was 4547.5 mg/L and an IgG 1930 mg/dL with the following high risk features: 8 prior lines of therapy including belantamab; high risk genomics (loss of TP53, amplification 1q, 13q deletion); extramedullary disease. The second patient was a 55 year old male with kappa light chain MM and R-ISS stage II disease at diagnosis. Prior to treatment, his kappa light chain was 1379.6 mg/L with the following high risk features: 8 prior lines of therapy; early progression following transplantation; high risk genomics with amplification of 1q; cirrhosis. Both patients received Teclistimab in standard step up followed by weekly dosing as per package insert immediately following hemodialysis (HD). Adverse events were similar to that reported on the MajesTEC-1 trial with only 1 grade 1 CRS event and both were promptly discharged to continue outpatient treatment without further CRS or neurotoxicity. They both achieved a prompt very good partial response with ongoing disease assessments planned. Importantly, no unexpected adverse events were noted.
Conclusions: Severe manufacturing shortages of BCMA directed CAR-T therapy (idecel and ciltacel) are daunting with no clear solution in sight. Thus an efficacious bispecific antibody targeting BCMA is sorely needed. Cytopenias and CKD/ESRD would have made both of our patients above ineligible for the MajesTEC-1 trial. Based on the clinical trial data, pharmacodynamics, pharmacokinetics, and experience with other bispecific antibodies, we elected to dose teclistamab in these ESRD patients immediately following HD. Teclistamab can be safely given to high risk RRMM patients with ESRD without unexpected adverse events and responses on par with the MajesTEC-1 trial. Although this preliminary report is promising, further research is warranted and with several other bispecific antibodies showing promising responses in RRMM, our experience should guide further treatments in this challenging patient population.
