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Dexamethasone Shows Promise as Cost-Effective Alternative to Tocilizumab for Cytokine Release Syndrome in RRMM
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Use of dexamethasone over tocilizumab was associated with significant cost-savings for patients with relapsed/refractory multiple myeloma (RRMM).
As few as one 10-mg dose of dexamethasone was safe and efficacious over tocilizumab (Actemra; Genentech) for management of cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (RRMM) receiving teclistamab (Tecvayli; Janssen Biotech, Inc.). Additionally, use of dexamethasone over tocilizumab was estimated to substantially reduce the cost of CRS management therapies.
Microscopic view of multiple myeloma cells attacking bone marrow | Image Credit: © Diane - stock.adobe.com
CRS is a common adverse event seen in patients with RRMM who receive treatments such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs). It is a systemic inflammatory response that is triggered by the overactivation of T-cells, leading to fever, hypotension, and dyspnea. Tocilizumab and dexamethasone are the recommended therapies for management of CRS, according to lymphoma experts and the International Myeloma Working Group (IMWG); however, recommendations on the order of administration of these agents in patients with grade 1 or 2 CRS differ. Lymphoma experts suggest dexamethasone prior to tocilizumab, whereas the IMWG recommends tocilizumab first due to its rapid reduction in CRS symptoms and decreased incidence of recurrent CRS.
Steroids as the first line of treatment for BsAb-related CRS are still not well established, despite the fact that consensus recommendations for non-Hodgkin lymphoma and MM may differ. In the retrospective analysis, the authors studied the safety and efficacy of using dexamethasone alone for CRS control in patients taking teclistamab for RRMM to encourage outpatient usage and reduce costs.
The study included health data from 243 patients with RRMM who initiated teclistamab between August 2022 and July 2024 across 6 United States academic medical centers. The median age was 69 years (range: 32-89), of which 51% were female and 72% were non-Hispanic White. The median prior lines of therapy were 5 (range: 3-18), and 87% of patients were triple-class refractory. With the exception of 24-hour urine tests, therapy responses were assessed using IMWG criteria, and both CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy criteria.
The patients received teclistamab subcutaneously as step-up doses of 0.06 mg per kg and 0.3 mg per kg, followed by weekly doses of 1.5 mg per kg. Step-up doses were separated by 2 to 3 days (days 1, 4, and 7, or days 1, 3, and 5) and administered either in the inpatient or outpatient setting based on institutional preference. At a median follow-up of 8.8 months, the overall response rate (ORR) was 66%, with 38% achieving a complete response or better, whereas median progression-free survival (PFS) and overall survival were 6 and 14.3 months, respectively.
CRS occurred in 55% of patients (n = 133), of which 41% experienced a grade 1 event and 13% experienced a grade 2 event. Two patients developed grade 3 CRS, and 1 experienced a grade 4 event, all of which resolved with dexamethasone, tocilizumab, and vasopressor support in the ICU without necessitating treatment discontinuation. CRS occurred following the first step-up, second step-up, and initial treatment doses in about 25%, 25%, and 21% of patients, respectively, with recurrent CRS observed in 13% after subsequent teclistamab doses. ICANS was reported in 13% of patients, including 3% with grade 3 and 4 events.
Dexamethasone was used in 31 patients (23%), tocilizumab in 38 (29%), dexamethasone and tocilizumab in 30 patients (23%), and 34 (25%) received supportive care only, which included observation, acetaminophen, oxygen, and/or hydration for CRS management.
Depiction of cytokine release syndrome and overactivated T-cells | Image Credit: © Kanisorn - stock.adobe.com
In the dexamethasone monotherapy group, 85% of patients experienced grade 1 and 15% experienced grade 2 CRS. In 73% of CRS occurrences, dexamethasone 10 mg was administered at dosages ranging from 4 mg to 20 mg. For recurrent CRS, 30% of patients needed a second dosage of dexamethasone, with a median of 1 dose (range: 1-5). Patients who needed more than 2 doses (15%) were prescribed 10 mg of dexamethasone every 6 hours until the CRS resolved. In about 27% of the patients, step-up doses were postponed for a median of 1 day (range: 1-5), and the median duration of CRS was 1 day (range: 1-4).
Grade 1 and 2 incidents occurred in 68% and 32% of individuals in the tocilizumab group, respectively, of which 3 patients needed several doses of tocilizumab (range: 2-5), whereas the remainder (92%) only received 1 dose. Following an additional teclistamab dose, 6 patients (16%) developed recurrent CRS, with a median CRS duration of 1 day (range: 1-4). A median of 1 day was lost in step-up doses for 21% of patients treated with tocilizumab. The incidence of ICANS did not differ between the groups (P = .7).
The ORR rates in each group were 73% and 74% in the dexamethasone and tocilizumab groups, respectively, with the majority in both groups achieving very good partial responses or better. The median PFS was not reached in the dexamethasone arm, whereas the tocilizumab group achieved a PFS of 6.7 months (P = .195).
The findings suggest patients experiencing grade 1 CRS with teclistamab may be safely treated with as few as one 10-mg dose or dexamethasone without the need for additional tocilizumab. Although more patients in the dexamethasone group experienced repeat CRS after a subsequent teclistamab dose (42% vs 16%, P = .018), all repeat events were of the same or lesser grade, and all but 2 events were managed with repeat dexamethasone administration.
The authors also noted the significant potential cost savings of using dexamethasone over tocilizumab. Using the average wholesale price (AWP) for the branded product, the cost of tocilizumab for grade 1 CRS alone amounts to $165,724. However, replacing 26 doses of tocilizumab with 26 doses of dexamethasone at 10 mg each would have resulted in a cost savings of $165,642, given an AWP of $3.13 per 10 mg dose of dexamethasone.
These findings highlight dexamethasone as a safe and cost-effective alternative to tocilizumab for managing grade 1 CRS in patients receiving teclistamab for RRMM. Given the substantial cost savings associated with dexamethasone use, further research and real-world data could help refine CRS management strategies and support broader adoption of steroids as a first-line approach in select patients.
