Dexamethasone for the Management of CRS Related to Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma

Introduction:

Teclistamab (tec) is a BCMA-directed bispecific antibody approved for patients with relapsed/refractory multiple myeloma (RRMM). In the pivotal MajesTEC-1 trial, cytokine release syndrome (CRS) occurred in 72.1% of patients and was primarily managed with tocilizumab (toci), with only nine patients receiving dexamethasone (dex) alone. Recently, the IMWG released guidelines supporting the use of toci for grade 1 and 2 CRS before dex. In this multi-center retrospective study, we evaluated tec CRS management with dex alone compared to toci alone.

Methods:

Six US academic medical centers contributed data on 242 patients with RRMM who initiated commercial tec as of May 2024. Baseline characteristics were outlined by descriptive analysis. All patients received pre-medications and tec in a step-up dosing manner as per the package insert. Patients received toxicity management and supportive care per institutional protocols. Toci was dosed at 8mg/kg (max 800mg). Dex doses varied by institution and ranged from 4 to 20mg. Responses were evaluated using IMWG criteria. CRS/ICANS were graded using the ASTCT criteria. Outcomes included incidence and severity of CRS, immune effector cell associated neurotoxicity syndrome (ICANS), treatment-related mortality (TRM), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results:

Of the 242 patients included, the median age was 69 years (range 32-89) and 51% were female. Median prior lines of therapy was 5 (range 3-18), and 86% of patients were triple class refractory. One hundred thirty-two (55%) patients experienced CRS (40% grade 1/14% grade 2). Two grade 3 and one grade 4 event resolved with intensive care. CRS occurred after the first and second step-up doses and first treatment dose in 25%, 24%, 21% of patients, respectively. The median duration of CRS was 1 day (range 0.5-6). Two patients received prophylactic toci without CRS. ICANS was observed in 12% of patients with 3% having grade 3-4 events. At a median follow-up of 8.4 months, the ORR was 65% (49%≥VGPR, 38%≥CR). The mPFS and mOS were 6 and 14.3 months, respectively.

Of the 132 patients with CRS, dex was used in 30 patients (23%), toci in 38 (29%), 30 patients (23%) received both dex+toci, and 25% received supportive care only (observation, acetaminophen, oxygen and/or hydration) for CRS management. Of the 30 patients in the dex+toci group, 11 received dex prior to toci. Of those 11, 6 received dex for ICANS and 2 of the remaining 5 received subsequent toci due to grade 2 CRS not resolved with dex.

The toci group had a numerically higher proportion of patients with high-risk cytogenetics (62% vs 51%, p=0.59) and triple-class refractoriness (85% vs 77%, p=0.53). The dex group had a higher proportion of patients with R-ISS stage III disease (47% vs 30%, p=0.35) but both groups were similar in regard to median age (70 vs 68), performance status ≥2 (20% vs 24%, p=0.76), extramedullary disease (30% vs 27%, p=0.96), and refractoriness to prior BCMA-directed therapy (40% vs 38%, p=0.98).

Of the 89 CRS events reported in the dex and toci monotherapy groups (68 patients), 47 (40 grade 1, 7 grade 2) were managed with dex and 42 (31 grade 1, 11 grade 2) with toci. Dex 10mg was used in 80% of CRS events in the dex group. While more patients in the dex group experienced a subsequent CRS event (43% dex vs 16% toci, p=0.016), there were 3 grade 2 events and no grade 3+ CRS events. All dex patients experiencing subsequent CRS were re-dosed with a median of 2 dex doses (range 2-5). Four patients in the dex group remained admitted for >48hr after the first treatment dose. Median duration of CRS was 1 day for both groups and step-up doses were delayed a median of 1 day in 26% and 21% of patients in the dex and toci groups, respectively (p=0.78). Rates of ICANS were similar between groups.

Best ORR was similar (73% vs 76%) in both groups and to that of overall population (65%). Median PFS was not reached in the dex group vs 6.6 months in the toci group (p=0.88). No TRM was observed in either group.

Conclusion:

Although more patients experienced subsequent CRS after dex treatment, recurrent CRS was low grade and manageable with repeated dex. When compared to the overall and toci groups, the dex group had similar efficacy outcomes. While considering advantages over toci in regard to availability, ease of use, and cost, this study highlights the feasibility of dex for the management of CRS in patients receiving tec.