CONTEXT: Negativization of CD38 marker in plasma cells after daratumumab
treatment

OBJECTIVE: To describea case of negativization of CD38 plasma cell (PC) marker

DESIGN: Case report of patient treated with Daratumumab

SETTING: A public reference oncology center in Colombia.

PATIENTS OR OTHER PARTICIPANTS: Multiple Myeloma patient

INTERVENTIONS : Chemotherapy as part of the institutional treatment

MAIN OUTCOMES MEASURES: To describe the clinical presentation, follow up and response of a patient treated with daratumumab who reached partial response even after CD38 negativization

RESULTS: Baseline characteristics:  A 63 years-old male patient diagnosed with multiple myeloma who requires Daratumumab as part of treatment in eighth line of management

Case Report: Multiple myeloma which was treated on 2011 with PAD regimen as front line. Complete response and posterior consolidation with Autologous stem cell transplant. Relapse two years after. Several rescue treatments were given without any response: Lenalidomide+Dexamethasone, CyBorD, Carfilzomib+Dexamethasone, Cyclophosphamide+ Dexamethasone, VRD. Flow Cytometry showed 63.5% of PC with expression of CD38+ (CD38/CD138=63.5% and CD38/CD56 = 63.5%), CD138, CD56, Beta-2 microglobulin, cytoplasmic kappa light chain. CD19 negative, CD45 Negative. 

Afterwards, a Daratumumab+Lenalidomide+Dexamethasone regimen was started. After 4 cycles of treatment a response evaluation was performed documenting partial response. Nevertheless, flow cytometry documented 4.8% of abnormal PC in bone marrow CD38 Negative (CD38neg/CD138pos = 4.8%, CD38neg/CD56 = 4.8%). CD138+, CD56+, Beta-2 microglobulin, cytoplasmic kappa light chain. CD19 negative, CD45 Negative.

CONCLUSIONS: Reduced surface CD38E in PC may confer protection against
daratumumab. Nevertheless the continuing response in our case raises several
hypothesis: The monoclonal antibody used for plasma cell identification could share an epitope with daratumumab ending up in a lack of identification by flow citometry. Redistribution of CD38 marker, formation of distinct polar aggregates, and subsequent release of tumor microvesicles. However, if a real lack of CD38E would be present or a clonal evolution or resistant mechanism would had happened, there are a lot of different mechanisms whose Daratumumab could be having activity against PC, keeping the response, like T-CD8 lymphocyte activation, complement pathway activation, lack of cell–cell and cell–matrix contacts reducing PC survival related to down of CD38E.

18 / CD38: From positive to negative expression after Daratumumab treatment. Case Report