BCMA/CD19 dual-targeting CAR T-cell therapy in older patients with newly diagnosed multiple myeloma: a phase 1 study

Area of Science:

• Hematology
• Immunotherapy
• Oncology

Background:

• CAR T cell therapy is not routinely studied in older patients with newly diagnosed multiple myeloma (NDMM).
• Older NDMM patients (age ≥70) represent a population with unmet therapeutic needs.
• Assessing novel therapies in this demographic is crucial for advancing multiple myeloma treatment.

Purpose of the Study:

• To evaluate the safety and efficacy of AZD0120, a BCMA and CD19 dual-targeting CAR T cell product, as a frontline therapy for older patients with NDMM.
• To assess AZD0120 in both frail and non-frail patients aged ≥70.
• To determine the preliminary response rates and toxicity profile of AZD0120 in this specific patient group.

Main Methods:

• Single-arm, phase 1 study involving 8 NDMM patients aged ≥70.
• Patients received VRD induction followed by AZD0120 infusion at two dose levels (1.5x10^5 or 3x10^5 cells/kg).
• Patients were stratified into frail (n=4) and non-frail (n=4) subgroups based on the IFM Simplified Frailty Score.

Main Results:

• All 8 patients achieved stringent complete response (sCR) and minimal residual disease (MRD) negativity at 1 month.
• High MRD negativity rates (100%) were observed at months 6 and 12 in evaluable patients.
• Most common Grade ≥3 TEAEs were hematologic toxicities; 50% experienced Grade 1 cytokine release syndrome (CRS), with no ICANS observed.
• Two frail patients showed improvement in ECOG status post-infusion.

Conclusions:

• AZD0120 demonstrates promising preliminary efficacy, achieving high rates of sCR and MRD negativity in older NDMM patients.
• The dual-targeting CAR T cell therapy exhibits a manageable safety profile with predominantly hematologic toxicities and low-grade CRS.
• AZD0120 represents a potential new frontline treatment option for older adults with newly diagnosed multiple myeloma.