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Objective To investigate the efficacy and safety of daratumumab combined with bendamustine in patients with relapsed/ refractory multiple myeloma complicated by secondary extramedullary disease. Methods The clinical data of patients with relapsed/ refractory multiple myeloma complicated by secondary extramedullary disease hospitalized in Guangxi Medical University Cancer Hospital from January 2021 to December 2023 were analyzed retrospectively. All patients had progressive disease on at least 3 prior treatment lines and followed by combination therapy with daratumumab and bendamustine. The efficacy and safety of the treatment were assessed based on the International Myeloma Working Group (IMWG) criteria and the National Cancer Institute⁃Common Terminology Criteria for Adverse Events (NCI⁃CTCAE) version 5.0. Results A total of 12 patients were included in the analysis, with 2 achieving complete response, 4 achieving partial response, 2 achieving minimal response, 1 achieving stable disease, and 3 experiencing progressive disease. The overall response rate was 50%, and the median progression-free survival was 8 months. All patients experienced hematological toxicity, 4 of which were grade Ⅲ-Ⅳ. Additionally, 3 patients developed pneumonia during treatment, no treatment⁃related deaths occurred. Conclusions The combination of daratumumab and bendamustine demonstrates effectiveness in treating relapsed/refractory multiple myeloma complicated by secondary extramedullary disease, with manageable toxicities. This result deserves further investigation with a larger patient population. [ABSTRACT FROM AUTHOR]

Objective To investigate the reasonable serological detection method by analyzing the characteristics of anti-K and anti-Wra from a patient who received treatment with daratumumab. Methods Unexpected antibody screening and identification were performed by saline method, polybrene, cardioagglutinin, dithiothreitol (DTT) treatment, trypsin treatment and papain treatment in the patient's plasma and acid elution solution. Heat elution test was detected after absorbing patient serum with K antigen negative red blood cells. The characteristics of antibodies were analyzed and their titer was continuously detected. Cross matching was performed after excluding interference of daratumumab. Results Anti-K and anti-Wra were detected in saline and polybrene in the patient's plasma. The patient's elution solution contained daratumumab. DTT or trypsin treatment excluded interference of daratumumab but papain treatment did not. DTT treatment destroyed K antigen and missed the detection of IgG antibodies in the Kell system. Trypsin treatment did not affect K antigen and can detect IgG antibodies of Kell system(anti-k)in the serum of the patient treated with daratumumab. Anti K was IgM and the titer was 4 by saline method and it decreased to no agglutination in room temperature after 39 days. Anti-Wra was IgG and the titer by polybrene method was 4, and it decreased to 1 after 39 days. After 76 days, neither anti-K nor anti-Wra could be detected. Transfusions of K and Wra antigen negative red blood cells were safe and effective. Conclusion DTT treatment can exclude interference of daratumumab, but attention should be paid to missed detection of anti-K. To avoid interference of daratumumab and identify unexpected antibody, multiple methods such as DTT treatment, polybrene and trypsin treatment in combination are recommended.

Objective To observe the reversal effect of thalidomide on drug resistance of daratumumab in transplanted myeloma in nude mice and to explore the related mechanism. Methods Balb/c nude mice were divided into the blank group (n=10), model group (n=10), and experimental group (n=10), respectively. The MPC-11 cells of plasmacy‐ toma in the logarithmic growth phase were inoculated into the right axilla of nude mice in the model group and experimental group to establish the models of subcutaneous myeloma in nude mice. In the experimental group, 144 mg/kg was injected subcutaneously on the 1st and 8th days after tumor formation, and 15 mg/kg thalidomide was given to the stomach at 48 h after the first subcutaneous injection of daratumumab, once a day； while in the blank group and model group, distilled wa‐ ter was given daily. In the experimental group, NK cell depletion was detected at different time points after daratumumab injection； in the experimental group, we detected the NK cell changes before the first dose of daratumumab, and NK cell depletion point after daratumumab injection on day 3 of thalidomide and at the second dose of daratumumab. After the experiment, flow cytometry was used to detect NK cells and CD38 expression in each group. ELISA was used to detect interleukin (IL)-15, IFN-γ, and tumor necrosis factor (TNF)-α in nude mice serum. Results After injection of daratumum‐ ab， the number of NK cells in the experimental group increased at first， reached the highest at 24 h， and then decreased. The number of NK cells in the model group was lower than that in the blank group， while the number of NK cells in the experimental group was higher than that in the model group (all P<0. 01). The expression of CD38 in the model group was higher than that in the blank group， while the expression of CD38 in the experimental group was lower than that in the mod‐ el group(both P<0. 01). The numbers of NK cells in nude mice of the experimental group were 3. 25 ± 0. 23，12. 65 ± 1. 27，26. 48 ± 0. 66， and 37. 67 ± 1. 45， respectively， before the first administration of daratumumab， at the time point of depletion of NK cells after injection of thalidomide， on the third day after administration of thalidomide and before the second administration of daratumumab， showing an increasing trend. The serum levels of IL-15， IFN-γ， and TNF-α in the model group were higher than those in the blank group (all P<0. 05)， and the levels of IL-15 and IFN-γ in the experimental group were higher than those in the blank group (all P<0. 01). Conclusions The depletion of NK cells is one of the important reasons for the drug resistance of myeloma cells to daratumumab. Thalidomide may reverse the drug resistance of transplanted myeloma cells to daratumumab by alleviating the depletion of NK cells and regulating the expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

Renal light chain amyloidosis (AL amyloidosis) had poor prognosis before the 21st century. However, the treatment of AL amyloidosis has made great progress in the last decade. We reviewed traditional treatments of AL amyloidosis such as alkylating agents, proteasome inhibitors, and recent advances such as monoclonal antibodies. Bortezomib improved the hematological response and survival effectively of the patients, and the combination of Daratumumab brings faster and deeper hematological response, increasing the response rate of target organs such as the kidneys and heart. The renal response was significant higher in the patients with the therapy of Daratumumab, part of them could achieve very good partial response or better renal response. Autologous hematopoietic stem cell transplantation(auto-HSCT)improves hematological as well as organ response, and could be the first choice among eligible patients. Kidney transplantation is a feasible option for those with good hematological response.

OBJECTIVE: To probe into the efficacy of daratumumab combined with lenalidomide and dexamethasone in the treatment of elderly refractory multiple myeloma and its short-term prognosis. METHODS: A total of 82 patients with multiple myeloma admitted to Huanggang Central Hospital from Jan. 2020 to Jan. 2022 were selected as research objects, those patients were divided into 41 cases in the observation group ( treated with daratumumab combined with lenalidomide + dexamethasone ) and 41 cases in the control group ( treated with lenalidomide + dexamethasone ). The efficacy, degrees of myelosuppression, grades of peripheral neuropathy, incidences of adverse drug reactions and short-term prognosis of both groups were observed. RESULTS: The strict complete remission rate of the observation group was 21. 95% (9 / 41), which was higher than 4. 88% (2 / 41) of the control group, with statistically significant difference ( P < 0. 05). After treatment, the proportion of degree Ⅱ of myelosuppression was 7. 32% (3 / 41) in the observation group, lower than 26. 83% (11 / 41) in the control group, with statistically significant difference (P< 0. 05). After treatment, the percentage of grade Ⅱ and grade Ⅰ-Ⅳ of peripheral neuropathy were respectively 4. 87% (2 / 41) and 24. 39% (10 / 41) in the observation group, lower than 26. 83% (11 / 41) and 48. 78% (20 / 41) in the control group, with statistically significant differences (P<0. 05). There was no statistically significant difference in total incidences of adverse drug reactions between two groups (P> 0. 05). The M protein content, abnormal plasma cell, β2-microglobulin and blood calcium value of the observation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.

Objective: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI)., Methods: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed., Results: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M 2 ). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections., Conclusion: Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Objective: To modified the classic dithiothreitol (DTT) method for treating red blood cells (RBCs) in Technical Manual of American Association of Blood Banks（AABB） and evaluate its application value in pre-transfusion examination of patients treated with daratumumab., Methods: The classic 0.2 mol/L DTT method was improved in terms of PBS, DTT concentration, donor RBCs concentration (suspended/packed) and sample processing time. The modified DTT methods and AABB classic DTT method were applied to the blood matching tests of 12 multiple myeloma patients treated with daratumumab. The effect of treating panel RBCs with modified DTT methods on the detection of other irregular antibodies was evaluated by using antiserum and antibody reagents with known antibody properties., Results: Two modified DTT methods were established (method 1: changed the concentration of DTT to 0.01 mol/L; method 2: changed the concentration of DTT to 0.02 mol/L and replaced the packed RBCs with 3% RBCs suspension). The optimal treatment time was 35 min for the modified DTT methods. At this time, the pan-agglutination caused by daratumumab was eliminated, but the detection of antibodies such as anti-E, anti-JK a , anti-M were not affected, and the titer of anti-K antibodies was only slightly decreased., Conclusion: The modified DTT methods were effective, which can eliminate the interference of daratumumab while retaining the activity of the Kell blood group system, and can replace the current classic DTT method in AABB Technical Manual.

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Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.

Objective: To investigate the interference of daratumumab on immunofixation electrophoresis after treating plasma cell diseases and methods to eliminate the interference. Methods: Serum samples of eight patients with plasma cell diseases treated with daratumumab in Peking University People's Hospital from April 2020 to March 2021 were collected for standard immunofixation electrophoresis and Hydrashift 2/4 daratumumab assay. Results: After treatment, 81.3% (13/16) of the samples showed drug-induced monoclonal antibodies (IgG-κ) . The samples without drug-induced monoclonal bands were related to individual differences, administration intervals, and immunoglobulin levels. Among the samples with IgG-κ monoclonal bands, 76.9% (10/13) could be directly identified as endogenous or exogenous monoclonal bands by immunofixation electrophoresis, and the others (3/13) could be identified by Hydrashift 2/4 daratumumab assay. Conclusion: Hydrashift 2/4 daratumumab assay can remove the band of daratumumab on the immunofixation electrophoresis and help with efficacy evaluation.

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) . Methods: The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed. Results: All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively ( P =0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P =0.033; OS: 6.3 months vs not reached, P =0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P =0.004) . Conclusion: Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM). Methods: The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People's Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019. Results: Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab. Conclusion: Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.