Fixed-Duration Elranatamab Consolidation Enhances MRD-Negativity Following CAR T Therapy

Elranatamab (Elrexfio; Pfizer) consolidation deepened minimal residual disease (MRD)-negativity in patients with relapsed/refractory multiple myeloma (R/R MM) following treatment with standard of care (SOC) idecabtagene vicleucel (ide-cel, Abecma; Celgene Corporation/Bristol Myers Squibb). The findings from the phase 2 EPIC study (NCT06138275) were presented at the 2025 International Myeloma Society Annual Meeting in Toronto, Canada.¹

Ide-cel is the first FDA-approved chimeric antigen receptor (CAR) T-cell therapy for adult patients with R/R MM after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The decision was based on statistically meaningful results from the phase 2 KarMMa trial (NCT03361748), which showed ide-cel had overall response rates (ORR) of approximately 70% and 85% in younger and older patients, respectively. Ide-cel also led to significant improvements in progression-free survival (PFS) and depth of response.^2,3

“There is an opportunity to improve the depth and durability of responses with ide-cel,” the authors wrote. “Our hypothesis is that elranatamab consolidation 100 days after ide-cel could reinvigorate polyclonal T-cell responses against BCMA-positive MM cells at a point when both cytopenias after CAR T are commonly resolved and the CAR T-cell population has decreased substantially.”⁴

EPIC is a single-arm, nonrandomized, prospective phase 2 study evaluating the use of elranatamab as a consolidation therapy in patients with R/R MM after 2 or more lines of treatment who received ice-cel as SOC. Patients receive a fixed-duration elranatamab consolidation beginning on day +100 and continuing through day +160 following ide-cel infusion. The elranatamab schedule consists of cycles 1 and 2 administered on days 1, 4 (cycle 1 only), 8, 15, and 22, followed by cycles 3 through 6 administered on days 1 and 15. Patients with serum IgG less than 400 mg/dL are required to receive the herpes simplex virus/varicella-zoster virus vaccine and PJP prophylaxis. Intravenous immunoglobulin is also recommended.⁴

The primary end point of the study is PFS with key secondary end points including safety, complete response (CR)/stringent complete response (sCR), duration of response (DOR), MRD-negative conversion rate, time to MRD-negativity, and rate of sustained MRD negativity of greater than or equal to 6 or 12 months.⁴

As of the time of data presentation, 12 patients are enrolled, with 3 in screening and 6 patients having completed elranatamab consolidation. The median age of the patients is 71 years (range: 48–82), of whom 50% are female and 25% present with high-risk cytogenetics (del[17p], t[4;14], or t[14;16]). The patients received a median of 3 prior lines of therapy before ide-cel (range: 2–6).⁴

The median interval between ide-cel infusion and initiation of elranatamab was 113 days (range: 91–158). Five patients underwent step-up dosing in the outpatient setting. One patient experienced disease progression with an isolated plasmacytoma 329 days after ide-cel and 219 days after beginning elranatamab consolidation, which was managed with radiation therapy alone and did not require systemic treatment. At the time of reporting, all patients remained alive.⁴

Following ide-cel, disease responses included 4 patients with sCR, 2 with very good partial response (VGPR), and 6 with partial response (PR). Among the 6 patients who have since completed elranatamab consolidation, responses deepened to 5 sCR and 1 VGPR.⁴

Of the 6 patients with available minimal residual disease (MRD) assessments, 5 achieved undetectable MRD at the 10^-6 sensitivity threshold (uMRD⁶). Three of these patients converted from MRD-positive status after ide-cel to MRD negativity following elranatamab.⁴

Regarding safety, 42% of patients experienced cytokine release syndrome, and all cases were grade 1. Grade 3 adverse events included neutropenia (33%), anemia (8%), and those without attribution (50%; febrile neutropenia [FN], n = 1; lung infection, n = 1; hypertension, n = 1; hypophosphatemia, n = 1; neutropenia, n = 3). One patient was hospitalized due to FN. There were no reported cases of immune effector cell-associated neurotoxicity syndrome or grade 3 thrombocytopenia.⁴

These preliminary data from the phase 2 EPIC study suggest that fixed-duration elranatamab consolidation following ide-cel may deepen responses and increase MRD-negativity in patients with R/R MM. Importantly, consolidation was feasible beginning approximately 100 days post–CAR T infusion, with manageable safety and no new unexpected toxicities.

REFERENCES

1. Elranatamab in R/​R multiple myeloma. Clinicaltrials.gov. Updated August 13, 2025. Accessed September 22, 2025. https://clinicaltrials.gov/study/NCT06138275

2. Gerlach A. Large real-world study validates idecabtagene vicleucel outcomes seen in KarMMa trial. Pharmacy Times. July 15, 2025. Accessed September 22, 2025. https://www.pharmacytimes.com/view/large-real-world-study-validates-idecabtagene-vicleucel-outcomes-seen-in-karmma-trial

3. Efficacy and safety study of bb2121 in subjects with relapsed and refractory multiple myeloma (KarMMa). Clinicaltrials.gov identifier: NCT03361748. Updated May 23, 2025. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT03361748

4. Lei M, Puliafito B, Yee A, et al. Initial results of a phase 2 study to evaluate elranatamab (elran) post-idecabtagene vicleucel (ide-cel) consolidation (EPIC) in patients with relapsed/refractory multiple myeloma (RRMM). 2025 International Myeloma Society Annual Meeting. September 17, 2025, to September 20, 2025. Toronto, Canada. Abstract PA-051.