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To investigate severe autoimmune encephalitis (AE) in the intensive care unit (ICU) with regard to standard treatment in responsive patients and additional escalation therapies for treatment-refractory cases.This retrospective, single-center study analyzed medical records of ICU-dependent AE patients for clinical characteristics, treatments, prognostic factors, and neurological outcome as quantified by modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE).From 40 enrolled patients (median age = 52 years; range = 16-89 years) with AE mediated by neuronal surface antibodies (nsAb; 90%) and AE with onconeuronal antibodies (10%), 98% received first-line therapy. Of those, 62% obtained additional second-line therapy, and 33% received escalation therapy with bortezomib and/or daratumumab. Good neurological outcome, defined as mRS = 0-2, was observed in 47% of AE with nsAb (CASE = 5), 77% of anti-N-methyl D-aspartate receptor encephalitis patients (CASE = 1), whereas AE patients with onconeuronal antibodies had the poorest outcome (mRS = 6, 100%). Treatment-refractory AE patients with nsAb requiring escalation therapy achieved similarly good recovery (mRS = 0-2, 39%, CASE = 3) as patients improving without (mRS = 0-2, 54%, CASE = 4), although they presented a higher disease severity at disease maximum (mRS = 5 100% versus 68%, CASE = 24 versus 17; p = 0.0036), had longer ICU stays (97 versus 23 days; p = 0.0002), and a higher survival propability during follow-up (p = 0.0203). Prognostic factors for good recovery were younger age (p = 0.025) and lack of preexisting comorbidities (p = 0.011).Our findings suggest that treatment-refractory AE patients with nsAb in the ICU can reach similarly good outcomes after plasma cell-depleting escalation therapy as patients already responding to standard first- and/or second-line therapies.

OBJECTIVE Whilst small-scale studies on rates of alloimmunisation of patients on Daratumumab have been undertaken, no large-scale study has been performed to date on this cohort of patients. BACKGROUND Patients with multiple myeloma (MM) who are relapsed or refractory to standard treatment are treated with the anti-CD38 therapeutic monoclonal antibody, Daratumumab. Due to the complexity of pre-transfusion compatibility testing, many MM patients in England are referred to Red Cell Immunohaematology (RCI) laboratories for investigation and provision of Red Blood Cell (RBC) components. METHODS Over a 4-month period, patients due to commence, or currently on anti-CD38 therapy were identified and flagged on the RCI Laboratory Information Management System (LIMS). Data was identified and extracted for further analysis. Interrogation of data was performed independently by two subject matter experts, with discrepancies resolved through further enquiry. RESULTS Of 734 English MM patients, we report an alloimmunisation rate of 0.4% whilst on an anti-CD38 TMAb. This is in line with other smaller cohort studies. CONCLUSION Given the low rate of RBC alloimmunisation, consideration should be given to revising the pre-transfusion testing regimen in this cohort. This may improve testing costs, turn-around times and evidence-based patient care.

Summary Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy‐related factors and was not yet evaluated. This single‐centre prospective study included MM patients tested for serological response 14–21 days post second vaccine. Vaccinated healthy volunteers served as controls. In all, 171 MM patients, median age 70 (38–94) were included; 159 active MM and 12 smouldering myeloma (SMM). Seropositive response rate (median titer) was 76% (91 U/ml) in active MM patients vs 98% (992 U/ml) in the 64 controls (P

Therapies in myeloma are rapidly advancing with a host of new targeted therapies coming to market. While these drugs offer significant survival benefits and better side-effect profiles compared with conventional chemotherapeutics, they raise significant difficulties in monitoring post-therapy disease status by flow cytometry due to assay interference and/or selection of phenotypically different sub-clones. The principal culprit, anti-CD38 monoclonal antibodies, limits the ability to detect plasma cells based on classical CD38/CD45 gating. Other markers, such as CD138, are known to be suboptimal by flow cytometry. Various techniques have been proposed to overcome this problem. The most promising of these techniques has been the marker VS38c, a monoclonal antibody targeting an endoplasmic reticulum protein which has shown high sensitivity for plasma cells. Alternative techniques for gating plasma cells, while variably effective in the near term are already the subject of several targeted therapies rendering their usefulness limited in the longer term. Likewise, future targets of these therapies may render present aberrancy markers ineffective in MRD testing. These therapies pose challenges that must be overcome with new markers and novel panels in order for flow cytometric MRD testing to remain relevant.

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.

Background Recent case reports have described the efficacy of daratumumab to treat refractory pure red cell aplasia (PRCA) following major ABO mismatched allogeneic hematopoietic stem cell transplantation (HSCT). In this report, we describe the use of daratumumab as a first-line agent for treatment of delayed red blood cell (RBC) engraftment following a major ABO mismatched pediatric HSCT and provide a review of the literature. Study design and materials We report on a 14-year-old with DOCK8 deficiency who underwent a myeloablative, haploidentical bone marrow transplant from her major ABO mismatched sister (recipient O+, donor A+) for treatment of her primary immunodeficiency. Despite achieving full donor chimerism, she had delayed RBC engraftment requiring ongoing transfusions. Due to iron deposition, symptomatic anemia, and persistence of anti-A iso-hemagglutinins despite discontinuation of immunosuppression, treatment for delayed RBC engraftment with the CD38-targeted monoclonal antibody daratumumab was selected as a less immunosuppressive agent that could more selectively target iso-hemagglutinin producing plasma cells without causing broad B-cell aplasia. Results Clinical effect with daratumumab was demonstrated by reduced iso-hemagglutinin titer, increased reticulocytosis, normalization of her hemoglobin, and transfusion independence. In the 11-month follow-up period to date, no additional transfusions or immunosuppression have been necessary, despite persistence of low-level anti-A iso-hemagglutinin. Conclusion Our experience suggests that daratumumab was an effective first-line therapy for delayed RBC engraftment and that earlier consideration for daratumumab in treatment of delayed RBC engraftment may be warranted.

We assessed the safety, efficacy, maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of selinexor, a first in class oral selective inhibitor of nuclear export (100 mg once weekly [QW] or 60 mg twice weekly), in combination with daratumumab (16 mg/kg per label) and dexamethasone (40 mg QW) (SDd) in patients with relapsed refractory multiple myeloma (RRMM). Thirty-four patients (median prior therapies, 3 [range, 2-10]) were enrolled; MM was refractory to proteasome inhibitor (PI) in 85%, immunomodulatory agent (IMiD) in 76%, both in 74%, and daratumumab in 6% of patients. Two dose-limiting toxicities (DLTs) were reported in the selinexor 60 mg twice-weekly cohort with no DLTs in the 100 mg QW cohort, making 100 mg QW the MTD and RP2D. Common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). Overall response rate was 73% and median progression-free survival 12.5 months in daratumumab-naïve patients. SDd was well tolerated and its promising efficacy suggests that further study of this PI- and IMiD-free regimen in RRMM patients who had at least one prior line of therapy including a PI and an IMiD but whose disease is naïve to daratumumab is warranted.

Daratumumab in combination with lenalidomide‐dexamethasone (D‐Rd) recently received FDA approval for the treatment of transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression‐free survival (PFS) in patients treated with D‐Rd in the MAIA trial and patients treated with common standard‐of‐care regimens from the Flatiron Health electronic health record‐derived deidentified database, which has data from patients treated primarily at community‐based oncology practices in the United States. Individual‐level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D‐Rd to bortezomib‐lenalidomide‐dexamethasone (VRd) and bortezomib‐dexamethasone (Vd); lenalidomide‐dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D‐Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D‐Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity‐score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D‐Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D‐Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head‐to‐head trials comparing D‐Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant‐ineligible patients with NDMM.

Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated. The median follow-up of the cohort is 14 months. The best overall haematologic response in evaluable patients was complete response (CR) in five (22%), very good partial response (VGPR) in five (22%) and partial response (PR) in seven (30%) patients for an overall response rate of 74%. Two of five patients in CR and two patients with initially detectable clones, but non-measurable immunoglobulins, had undetectable minimal residual disease (MRD) with next-generation flow cytometry (NGF) after therapy. Haematologic response rate for previously untreated patients was 83% vs. 69% for previously treated and for daratumumab combinations it was 91% vs. 64%, and with CR/VGPR 82% vs. 29%, compared to daratumumab monotherapy. At six months, 12/22 (55%) patients not on dialysis achieved a reduction of proteinuria >30%, of at least 0·5 g/24 h, without an estimated glomerular filtration rate (eGFR) reduction. The toxicity was mild and predictable. In conclusion, daratumumab-based therapy is a new option for patients with MGRS.

This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6 months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models. Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first 2 months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first 2 months of M-protein dynamic data were ~ 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2 months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM.

Daratumumab is approved for use in newly diagnosed and relapsed/refractory multiple myeloma (MM), however the patients most likely to benefit from its addition to standard anti-myeloma therapy is unclear. This meta-analysis included 2340 newly diagnosed MM patients (1982 with standard risk and 358 with high risk cytogenetics) and 673 patients with relapsed/refractory MM (513 with standard risk and 160 with high risk cytogenetics) to assess which cytogenetic subgroups derived PFS benefit from Daratumumab. Studies included were the CASSIOPEIA, MAIA and ALCYONE (for newly diagnosed MM) and the CASTOR and POLLUX trials (for relapsed/refractory MM). Daratumumab's addition led to a clear benefit in standard risk newly diagnosed MM (HR 0.43; 95% CI, 0.35-0.53

BACKGROUND Little is reported on the real-life impact of daratumumab in relapsed and/or refractory multiple myeloma patients (RRMM). We analyzed a cohort of 156 patients who received daratumumab as a single agent concerning ECOG status, eGFR, cytogenetics, lines of prior treatment, and their impact on survival. RESULTS Eighty-two (53%) patients were triple refractory, 54 (35%) patients were single or double refractory, and 20 (12%) patients were non-refractory. Following daratumumab treatment, the progression-free survival (PFS) in these groups was 7.2%, 11.4%, and 53% (P

A deep elucidation of the mechanisms of action of anti-CD38 monoclonal antibodies (mAbs), such as daratumumab (DARA), is required to identify patients with multiple myeloma (MM) who are more responsive to this treatment. In the present study, an autologous ex vivo approach was established, focussing on the role of the monocytes in the anti CD38-mediated killing of MM cells. In bone marrow (BM) samples from 29 patients with MM, we found that the ratio between monocytes (CD14+ ) and MM cells (CD138+ ) influences the response to DARA. Further, the exposure of the BM samples to DARA is followed by the formation of a CD138+ CD14+ double-positive (DP) population, that quantitatively correlates with the anti-MM cells killing. These effects were dependent on the presence of a CD14+ CD16+ monocyte subset and on high CD16 expression levels. Lastly, the addition of a mAb neutralising the CD47/signal-regulatory protein α (SIRPα) axis was able to increase the killing mediated by DARA. The effects were observed only in coincidence with high CD14+ :CD138+ ratio, with a significant presence of the DP population and were correlated with CD16 expression. In conclusion, the present study underlines the critical role of the CD16+ monocytes in DARA anti-MM killing effects and gives a rationale to test the combination of an anti-CD47 mAb with anti-CD38 mAbs.

Background Daratumumab (Dara), an anti‐CD38 monoclonal antibody, has an immunologic mechanism of action through targeting of CD38 expressing immune cells in patients with multiple myeloma (MM). Furthermore, it was recently shown that CD38 upregulation in tumors, is a major mechanism of acquired resistance to antiprogrammed cell death 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1). Therefore, we decided to evaluate the immunomodulatory effects of CD38 blockade by Dara on the PD‐L1 expressing immune cells. Methods We analyzed CD38 and PD‐L1 expression on immune cells at different time points in 18 newly diagnosed MM receiving bortezomib, lenalidomide and dexamethasone, with or without Dara. Results We first confirmed that CD38 is widely expressed on immune cells, with the strongest expression on plasmacytoid dendritic cells (pDC). Furthermore, Dara induces a strong depletion of pDC in addition to the well‐known rapid depletion of natural killer cells. Finally, we found that PD‐L1 expression on antigen‐presenting cells (APC) increases with MM treatment in patients that did not received Dara, while addition of Dara prevents this increase. Conclusion Overall, our results suggest new mechanisms of action of Dara through depletion of pDC and prevention of PD‐L1 upregulation expression on APC. Our finding provides new evidences for development of therapeutic strategies targeting both CD38 and PD‐L1/PD‐1 pathway in patients with MM., Daratumumab have immunomodulatory effects on CD38‐expressing immune cells. Daratumumab prevents PDL1 expression on CD38‐expressing antigen‐presenting cells.

Gain of chromosome 1q21 and the gene expression-based GEP70 risk score are established prognostic markers for newly diagnosed Multiple Myeloma (MM) patients. Here we addressed the prognostic impact of these two markers in 81 relapsed/refractory (RR) MM patients treated with the CD38-antibody daratumumab. Fluorescence in situ hybridization for 1q21 was performed at initial presentation, while the GEP70 score was determined at initial presentation and prior to daratumumab treatment. While the GEP70 at initial presentation showed a trend for inferior survival, the GEP70 collected prior to daratumumab treatment was significantly associated with poor outcome (P < 0·05). The worst outcome was seen for patients who were positive for gain(1q) and classified as GEP70 high risk prior to daratumumab [progression-free (PFS) and overall survival (OS) of 0·3 years (95% CI: 0·15-1·4 years) and 0·8 years (95% CI: 0·5-1·9 years) respectively], while the median PFS and OS were not reached by patients without gain(1q) and GEP70 low-risk status. In conclusion, gain(1q) and the GEP70 are powerful prognostic markers for RR MM patients treated with daratumumab, and patients classified as high risk according to these markers experience shorter treatment response.

Daratumumab was approved in patients with relapsed or refractory multiple myeloma (MM) who previously received proteasome inhibitors or immunomodulatory drugs. However, the efficacy and safety of the addition of daratumumab in subpopulations of patients with relapsed or refractory MM is still unknown. We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (inception to September 2020). All phase 3 randomized controlled trials (RCTs) which were conducted in patients with relapsed or refractory MM and compared the efficacy or safety with the addition of daratumumab versus control were adopted. Three studies including 1497 patients met our criteria. The addition of daratumumab increased the rates of overall response (RR 1.21, 95% CI 1.15–1.28, p, Daratumumab‐based therapy provides beneficial effects in patients with relapsed or refractory MM with an acceptable safety profile. The progression‐free survival benefit was consistent regardless of patient’s baseline characteristics or previous therapy agents

Background Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and interferes with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA. Materials and methods A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty-six MM patients received transfusion but not DARA were studied as control group. Results Totally 184 Ab screens were done on 45 patients transfused with ABO-Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screening positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period. Conclusions Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA-associated difference in the alloimmunization risk. No significant difference in alloimmunization is detected between ABO-Rh compatible and phenotypically matched transfusion.

Daratumumab, an anti-CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%-40%), and the median difference between involved and noninvolved free light-chains (dFLC) was 446 mg/L (range 102-1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7-28 days), and the median time to best hematological response was 64 days (range 7-301 days). The hematological overall response was 90%, with high-quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7-9.1). Infusion-related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow-up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function.

PURPOSE To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta-analysis. METHODS We searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma. RESULTS Six daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (≥CR) rate of 24%, very good partial response or better (≥VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P

Due to the rarity and fulminant nature of the condition, there are limited data driving dialogue for optimal treatment strategies for plasma cell leukemia (PCL). Additionally, the current diagnostic definition of PCL has not been prospectively studied which may result in delays to initiating early aggressive treatment due to underdiagnosis.

Background Daratumumab (DARA) is a humanized Immunoglobulin G(IgG)1-kappa monoclonal antibody against CD38 antigen that is shown to improve outcomes in relapsed/refractory plasma cell myeloma (PCM) patients. Since CD38 is expressed by different hematopoietic elements, DARA has the potential to interfere with flow cytometric assessment of bone marrow specimens. Methods Flow cytometric analysis of bone marrow samples from 10 PCM on DARA and 5 control samples was performed using two different antibody panels. Results Bone marrow samples from PCM patients on DARA exhibited a population of CD19+ CD10+ B-lymphoid cells with kappa light chain restriction. Further morphological and immunophenotypic studies suggested that this population represents marrow hematogones. Marrow hematogones from control samples showed normal immunophenotypic profiles. Conclusion DARA on the surface of hematogones interferes with flow cytometric clonality study leading to artifactual kappa light chain restriction, which can result in false interpretation of a concurrent clonal B-cell proliferation. In the era of rapidly growing list of therapeutic monoclonal antibodies, flow cytometry pathologists should be aware of potential interferences to avoid misdiagnosis. © 2019 International Clinical Cytometry Society.

BACKGROUND Daratumumab (DARA) is a human IgG1κ monoclonal antibody directed against CD38, approved for the treatment of multiple myeloma. As CD38 is expressed on RBCs, DARA can interfere with pretransfusion testing. DARA interference can be negated by denaturation of CD38 on RBCs with dithiothreitol (DTT) reagents. Because of this interference in pretransfusion testing, our hospital implemented a notification and testing/transfusion algorithm (NATTA) for pretransfusion testing and RBC product provision for DARA patients. This standardized approach combines DTT-based testing with selective genotyping and the provision of phenotypically similar RBCs for patients with clinically significant antibodies. STUDY DESIGN AND METHODS We evaluated pretransfusion test results and transfusion requirements for 91 DARA patients in an academic medical center over 1 year to determine the incremental cost of pretransfusion testing and RBC selection. The actual costs for the NATTA approach were compared to a theoretical approach using universal genotyping with a provision of phenotypically similar RBC transfusions. RESULTS The annual cost of testing related to DARA after NATTA implementation was $535.76 per patient. The simulated annual cost for the alternative genotyping with provision of phenotypically similar RBC transfusions approach was $934.83 per patient. CONCLUSION In our entire cohort of DARA patients, a DTT-based testing algorithm with selective genotyping and provision of phenotypically similar RBCs only for patients with clinically significant antibodies was less expensive than a simulated model of universal genotyping and provision of phenotypically similar RBCs.