Selection of anti-CD38 antibodies for flow cytometric detection of myeloma cells treated with daratumumab or isatuximab.

Treatment with the anti-CD38 therapeutic monoclonal antibodies (mAbs) daratumumab (DARA) and isatuximab (ISA) achieves deep responses in patients with multiple myeloma (MM), often resulting in measurable residual disease (MRD) negativity. CD38 is one of the key surface markers used for flow cytometric MRD assessment in MM; however, DARA is known to interfere with CD38 detection by conventional anti-CD38 mAbs. The impact of ISA on CD38 detection remains unclear. This study aimed to develop optimized methods for accurate detection of CD38 on MM cells by flow cytometry. The anti-CD38-variable heavy chain of heavy chain (VHH) Ab from the JK36 clone enabled clearer detection of surface CD38 on DARA-treated MM cells compared with the anti-CD38 multi-epitope (ME) Abs and anti-CD38 mAbs (T16 and HB7 clones). In contrast, in ISA-treated MM cells, the anti-CD38 mAbs demonstrated superior CD38 detection compared with the anti-CD38 ME Ab and anti-CD38 VHH Ab. These trends were confirmed in primary bone marrow samples from MM patients treated with anti-CD38 therapeutic mAbs. These findings underscore the importance of selecting appropriate anti-CD38 Abs based on treatment history to ensure accurate flow cytometric evaluation of MM cells in patients treated with DARA or ISA.