Abstract
Introduction: Elranatamab (Elra) is a BCMA-CD3 bispecific antibody (BsAb) approved for the treatment of relapsed and refractory multiple myeloma (RRMM) after 4 prior lines of therapy (LOT), but there is a lack of comprehensive data on its efficacy and safety profile in the real-world population.
Methods: We conducted a retrospective, single-center study of patients (pts) treated with Elra from 10/2023 to 05/2025 at Moffitt Cancer Center. Data on demographics, prior therapies, cytogenetics, and performance status were collected. Responses were assessed by IMWG criteria; toxicities per ASTCT consensus. Survival outcomes were estimated using Kaplan-Meier methods and Cox regression. Logistic regression identified factors associated with overall response rate (ORR; ≥PR).
Results: A total of 63 pts were identified, median age at initiation of treatment was 71 (range 45-95). Forty-four percent were female, 84% were white, 92% were triple-class refractory, and 59% were penta-class refractory. Twenty-nine percent had an ECOG of ≥2. A total of 56 patients (89%) were treated inpatient, while 7 patients (11%) were treated outpatient with prophylactic tocilizumab.
Median prior lines of treatment was 6 (range 2-15). Sixty-two percent of patients had previously been treated with an autologous hematopoietic cell transplant (autoHCT), 11% had prior treatment with another BsAb (talquetamab). Sixty-two percent had prior BCMA-directed therapy, the vast majority of which were CAR-T (90%). Median time from prior BCMA therapy to initiation of Elra was 16.6 months (range = 8.7-35.4). Seventy-six percent had high risk cytogenetics (gain/amp 1q, del 1p, del 17p, t(14;16), t(4;14)). Eleven percent had >5% circulating plasma cells within 30 days prior to treatment, and 19% had high marrow burden of disease (>50% marrow involvement).
ORR was 52%. There were no statistically significant differences in ORR for any other clinical variables except prior BsAb treatment (17% vs 68%, p=0.024). Median progression-free survival (PFS) was 10.1 months (95% CI 3.1-inf), and median follow-up time was 5.8 months (95% CI 1-18).
Eleven percent developed ICANS, with 8% grade ≥2. Thirty percent developed CRS, with 6% grade ≥2. Of note, no pts who received outpatient treatment developed CRS or ICANS grade ≥2. Forty-three percent developed an infection while undergoing treatment, including 8 viral and 18 bacterial with 15 requiring hospitalization.
In univariate analysis, high marrow burden of disease was associated with inferior OS (HR 3.92, 95% CI 1.37-11.24, p=0.006) and PFS (HR 3.45, 95% CI 1.39-8.53, p=0.004). High marrow burden of disease was also associated with decreased ORR (OR 0.22, 95% CI 0.05-0.95, p=0.043). Treatment with prior BsAb was associated with shorter PFS (HR 3.78, 95% CI 1.46-9.81, p=0.003) but no statistically significant difference in OS. Time from prior BCMA therapy of <12 months showed decreased OS compared to >12 months (HR 4.05, 95% CI 1.27-12.94, p=0.011). There was no statistically significant difference in PFS or OS based on prior autoHCT or high-risk cytogenetics.
In multivariate analysis, high marrow burden of disease was associated with shorter PFS (HR 2.92, 95% CI 1.09-7.83, p=0.033) and lower OS (HR 3.92, 95% CI 1.37-11.24, p=0.011). High marrow burden of disease was also associated with decreased ORR (OR 0.20, 95% CI 0.04-0.99, p=0.049). Prior BsAb use was associated with shorter PFS (HR 4.27, 95% CI 1.13-16.15, p=0.033). Other variables including prior autoHCT status, and high-risk cytogenetics did not show any significant impact on OS or PFS.Conclusions: Elra is a promising treatment for RRMM in the real-world setting. Infection rates remain a concern; however, these infections did not lead to discontinuation of treatment. CRS and ICANS were prevalent, however grade 2 or higher CRS or ICANS were infrequent. Interestingly, there was no increased risk of infection, CRS or ICANS with outpatient treatment. ORR remains impressive in this difficult to treat population but were lower in patients who had received a BsAb in the past. High marrow burden of disease was predictive of both lower PFS and OS.
