Background: Daratumumab is a human monoclonal antibody targeting CD38 used widely in various related conditions. Caution is advised when interpreting the pretransfusion tests in daratumumab-treated patients because they may show nonspecific reactions with red blood cells. This paper provides experimental evidence for the false-positive interference phenomena induced by daratumumab in in-vitro and ex-vivo experiments and experimental support for resolving it using dithiothreitol (DTT). Methods: Fifteen crossmatching pairs, four cardiac amyloidosis (CA) patients treated with daratumumab, and three healthy individuals were included. The flow cytometry crossmatch (FCMXM) was conducted with negatively selected T and B cells. After spiking the sera with 500 μg/mL daratumumab, the T and B cells were treated with DTT. The prospective FCMXM was conducted with the sera of CA patients treated with daratumumab. The CD38 expression levels in T, B, and NK cells were measured without and with a DTT or pronase treatment. Results: Five hundred μg/mL of daratumumab spiking was sufficient to elicit a false positive effect in T cell FCMXM. In particular, the administration of 0.1 M DTT efficiently resolved the induced false positivity in flow cytometry. Moreover, DTT caused a decrease in the CD38 expression levels in T, B, and NK cells. Conclusion A typical therapeutic dose of daratumumab causes false-positive FCMXM, which was effectively addressed by a DTT treatment. Therefore, information about the patient’s medical condition and the use of immunotherapeutics, such as daratumumab, is needed, given its impact on diverse CD38-expressing cells.

PURPOSE: This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer. MATERIALS AND METHODS: A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model. RESULTS: The 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029). CONCLUSION: The nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.
Brain ; Breast Neoplasms* ; Breast* ; Follow-Up Studies ; Humans ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Nomograms* ; Phenobarbital ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant* ; Recurrence