Camelid-derived CD38 antibody successfully circumvents epitope blockade by the therapeutic anti-CD38 antibody daratumumab

Abstract

Abstract Objectives To evaluate the efficacy of an anti-CD38 nanobody to detect plasma cells in a flow cytometry myeloma minimal residual disease (MRD) panel in patients treated with daratumumab and other immunotherapies. Methods Twenty-three bone marrow samples from as many patients were collected during or at the end of daratumumab treatment cycles. A 5-tube, 8-color flow cytometry MRD panel was performed. Dotplots were reviewed, and the median fluorescence intensity (MFI) was calculated. Results Patients’ ages ranged from 45 to 77 years, and the cohort was made up of 13 men and 10 women who had undergone 2 to 24 cycles of daratumumab therapy at the time of myeloma MRD testing. In all 23 cases, therapeutic use of daratumumab impaired pathologists’ ability to measure CD38 on plasma cells when using a conventional murine monoclonal antibody (anti-CD38 fluorescein isothiocyanate [FITC], clone T16; Beckman Coulter). In 21 of the 23 cases, the measurement of CD38 was restored when the anti-CD38 nanobody was employed. Compared with anti-CD38 FITC, the anti-CD38 Alexa Fluor 488 nanobody (Beckman Coulter) produced higher MFI and allowed measurement of a higher frequency of discernable plasma cells. Conclusions The camelid-derived CD38 antibody successfully circumvents the steric inhibition of CD38 that the therapeutic use of daratumumab imparts and facilitates myeloma MRD plasma cell detection.