Safety and Efficacy of Teclistamab in a Patient Series with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment on Dialysis

Background

Renal failure is a common and serious complication in multiple myeloma, linked to poor prognosis and an urgent

need for better treatments. Teclistamab, a BCMA-directed bispecific antibody, has shown over 60% efficacy in

refractory myeloma but lacks data in patients with severe renal impairment, who are routinely excluded from

clinical trials. Though antibodies are generally not renally cleared, there are significant concerns about the

hemodynamic side effects of cytokine release syndrome (CRS). Patients with renal failure are particularly

vulnerable to hemodynamic changes and may not tolerate the fluid resuscitation required for high-grade CRS.

CRS has shown worse outcomes in renal failure patients in conditions like COVID-19 infection. To address this

critical gap, we present a case series of relapsed/refractory multiple myeloma (RRMM) patients on chronic

hemodialysis treated with teclistamab.

Methods

We retrospectively reviewed RRMM patients with severe renal failure on dialysis treated with teclistamab at our

university hospital from late 2022 to May 2024. Patients were admitted for step-up dosing, starting at 0.06 mg/kg,

increasing to 0.3 mg/kg, and reaching 1.5 mg/kg on the third dose, per FDA approval guidelines.

Results

Four patients with RRMM were included in our study. They had a median age of 76 years (73-80) at teclistamab

treatment, and three were male. All patients presented with baseline free light chain (FLC) disease; three had

lambda FLC, and two tested positive for t(11;14) on cytogenetic testing. Each patient had received a minimum of

three prior therapies, including immunomodulators (IMiDs), proteasome inhibitors (PIs), and an anti-CD38

monoclonal antibody.

CRS and ICANS: CRS occurred in two patients. One experienced grade 1 CRS, managed with tocilizumab and dexamethasone,

while the other had possible grade 3 CRS, treated with corticosteroids, oxygen therapy, and fluid resuscitation.

No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.

Treatment Response: After initial treatment with teclistamab, three patients achieved at least a very good partial response (VGPR), and

one achieved a partial response (PR). The median time to response was 6.5 weeks (4-7), based on serum FLC

reduction.

Infection: One patient developed UTI sepsis caused by Enterococcus faecalis after continuous treatment for 2 months.

Despite aggressive treatments, including broad-spectrum antibiotics, IV fluids, and vasopressors, the patient died

from multiple organ failure due to sepsis.

Follow-up and Current Status: Patients have been followed for up to 8 years (2-14) from diagnosis, with a similar duration on dialysis, as all

patients initially presented with renal failure attributed to myeloma. As of the last follow-up, two patients are alive

and two have deceased. Among those alive, both are on active treatment with teclistamab, administered once a

week. Intravenous immunoglobulin (IVIG) was administered in all patients.

Conclusions

In summary, our experience with teclistamab in RRMM patients with ESRD and active hemodialysis diverges

significantly from published reports, which are predominantly derived from small series. Our cohort exclusively

comprises dialysis-dependent patients, some with oliguria, and highlights two fatalities: one from severe,

refractory CRS and ICANS, and another from a UTI following line-related sepsis due to enterococcal infection.

Most patients experienced manageable grade 1 CRS, promptly alleviated with early dexamethasone and

tocilizumab administration. These findings emphasize the critical need for dedicated clinical trials tailored to

address the complexities and outcomes specific to this challenging patient population.

No relevant conflicts of interest to declare.