(PA-342) Safety and Efficacy of Elranatamab in Patients with Daratumumab Relapsed And/or Refractory Immunoglobulin Light Chain Amyloidosis

In AL amyloidosis, plasma cell directed therapies must show efficacy and safety in the setting of cardiac and renal involvement. Based on data in multiple myeloma, we hypothesized that elranatmab, a BCMAxCD3 bispecific antibody, will induce rapid and deep hematological responses in AL amyloidosis patients, with an acceptable safety profile.

Methods:   This is a retrospective, multicenter series on 9 consecutive, Daratumumab-relapsed and/or refractory AL amyloidosis patients who received at least 1 full dose of elranatamab between February-September 2024 at Dana-Farber Cancer Institute/Brigham and Women’s Hospital or Columbia University Irving Medical Center. Patients were staged according to the 2004 Mayo Clinic criteria with European modifications.

Patients received pre-medications and step up doses (12mg on Day 1 and 32mg on Day 3) according to the package insert. Treatment doses of 76 mg were administered weekly thereafter with the schedule modified to Day 1 and 15 in those achieving a ≥VGPR after 1 – 2 cycles. Patients also received anti-viral and anti-pneumocystis prophylaxis. Cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were treated per IMWG consensus guidelines. Informed consent and IRB approval was obtained.  The data cut-off was February 5, 2025

Results:   

Of the 9 treated patients, 3 were refractory to frontline daratumumab-based regimens with 6 having relapsed disease after a median of 2 prior lines (range 1-4). Three patients had Mayo Stage 3A and 4 had 3B at diagnosis. The median baseline NT-proBNP was 2,164 pg/mL (range: 361-51,140) and baseline dFLC was 154.7 mg/L (range: 26.3–641.8) on C1D1 elranatamab. Three patients met IMWG criteria for overlapping multiple myeloma.

After a median follow up of 8.2 months, there was an ORR of 100% with 89% achieving ≥VGPR and 67% of patients achieving CR. The median time to response was 9 days with, 78% achieving dFCL < 10mg/L after the first cycle. MRD negativity 10^-6 (Clonoseq) was achieved by 4 patients, 10^-5 (multiparametric flow cytometry) in one patient, and not available in 4 patients. The median PFS is 8.2 months (range: 1.4-12.3). In the 5 patients evaluable for a cardiac response,2 achieved carVGPR and 3 for carPR. One patient was evaluable for renal response and achieved renCR after 6 cycles.

CRS occurred in 67% of patients (Grade 1-2: 5 patients, Grade 3: 1 patient); all occurring within 24 hours of C1D1. One patient developed Grade 2 ICANS within 24 hours of C1D1 that resolved within 3 days without any recurrence. Grade 2 neutropenia occurred in 1 patient and grade 1 thrombocytopenia occurred in another. Two frail patients in a hematological remission with Mayo Stage IIIB amyloidosis passed from progressive multiorgan failure, 103 and 44 days after C1D1, respectively.

Conclusions:   

Elranatamab appears highly effective and well tolerated in relapsed refractory AL amyloid patients, including those with advanced cardiac involvement, supporting prospective clinical trials.