P-047: Characteristics of Clinicopathological Features of 17 Patients Who had Relapsed Myeloma after Anti-BCMA CAR-T Therapy

Introduction: CART therapy targeting BCMA is increasingly employed in myeloma patients who have failed other lines of therapy. Despite remarkable improvement in response rate and survival, a subset of patients still suffers from relapsed disease. We performed this study to analyze the clinicopathological features of patients who had relapsed diseases after CART therapy against BCMA.

Methods: Patients who were treated with ide-cel (Abecma®) or cilta-cel (Carvykti™) and subsequently relapsed were identified from our database during the period of January 2020 to January 2024. Patients who had sufficient biopsy materials analyzed by morphology and ancillary studies including karyotyping or/and FISH using a panel for myeloma (9 probes) as well as flow cytometry using BCMA (clone 19F2, PE, Bio Legend) in combination with 8 other markers (CD38, CD138, CD45, CD19, CD27, CD56 and CD81) or immunohistochemistry for BCMA expression were included.

Results: We identified 17 patients, age ranged from 58-91 yrs old (median 68), 10 men and 7 women. Two patients received Cilta-cel and the remaining 15 patients received Idel-cel. The interval from CAR-T infusion to relapse ranged from 3-38 months (median 12 months). The relapse was diagnosed in a bone marrow biopsy in 11 patients with tumor estimated to be 10-90% (median 70%) of total cellularity. The relapse was confirmed at extramedullary sites in 6 patients, involving soft tissue (n=3), skin (n=2), CSF (n=1). BCMA assessed in the relapsed samples was strongly positive (n=4), weakly/partially positive (n=3) and negative (n=3). Two cases were not assessed for BCMA. Four patients had a complex karyotype with loss of 17p/TP53 in 3. FISH found CKS1B amplification in 9 patients, including 2 with additional FGFR3::IGH, TP53 deletion (n=2) and MYC rearrangement (n=2). Four of 6 patients whose samples were analyzed by next generation sequencing found TP53 mutations with VAF ranging from < 5-30%. The relapsed diseases were treated with additional therapy, including stem cell transplant, Teclistamab, anti-CD70 CAR-NK or other chemoimmunotherapy. With a median follow up of 19 months (range 3.5-58.4), Five patients died and the remaining 12 were still alive at the last FU, the median OS has not reached yet.

Conclusions: BCMA expression varied from bright to diminished or absent with majority retained in the relapse samples after the patients failed CART therapy suggesting immune evasion as a mechanism of resistance in majority. About 1/3 of patients suffered from extramedullary relapse despite negative bone marrow. The recurrent tumor cells typically harbored high risk genetic aberrations with a high frequency of CKS1B amplification, FGFR3::IGH, TP53 deletion or/and mutation, or MYC rearrangement.