Search

Summary: Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second‐line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti‐CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow‐up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow‐up end‐point since the patient achieved response) was 48, 175 and 204 days with the follow‐up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow‐up. No significant treatment‐related adverse events were found during follow‐up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored. [ABSTRACT FROM AUTHOR]

Background: With the increasing use of daratumumab (DARA)‐containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion‐related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90‐min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110‐min rapid DARA infusion regimen aimed at reducing the treatment burden on patients to guarantee therapeutic safety. Methods: MM inpatients treated with the DARA regimen were divided into two groups according to the number of times the DARA regimen was used: a standard infusion regimen for patients treated with the first two doses of DARA and a 110‐min rapid infusion regimen for patients treated with more than two doses of DARA. Anti‐allergy medications were routinely administered prior to the start of DARA infusion, patient consent, and authorization was obtained for all treatments, and statistical evaluation of the results was conducted via descriptive analyses, one‐way ANOVA and chi‐square tests. Results: A total of 129 patients were included in this study: 68 in the standard infusion group, with 121 DARA infusions, and 129 in the rapid infusion group (patients who participated in the standard infusion subsequently participated in the rapid infusion), with 738 DARA infusions. The incidence of IRRs was 27.27% (36/121) in the standard infusion group and 1.35% (10/738) in the rapid infusion group, which were significantly different (p < 0.001). The incidence of IRRs after rapid infusion in other studies was <6%. The incidence of grade 1 IRRs in the rapid infusion group was 0.81% (6/738), the incidence of grade 2 IRRs was 0.54% (4/738), and there were no IRRs above grade 3; age, sex, and underlying disease had no effect on the choice of infusion method (p > 0.05). The mean infusion time after the occurrence of IRRs was also shorter in the rapid infusion group than in the standard infusion group (F = 24.781, p < 0.001). Conclusion: The 110‐min rapid infusion DARA regimen is feasible and safe for use in Chinese MM patients. [ABSTRACT FROM AUTHOR]

Background: Comparative investigations evaluating the efficacy of pomalidomide‐based (Pom‐based) versus daratumumab‐based (Dara‐based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real‐world studies. Methods: This retrospective cohort study included 140 RRMM patients treated with Pom‐based or Dara‐based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. Results: The overall response rates (ORR) for Pom‐based (n = 48), Dara‐based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression‐free survival (PFS) was 5.7 months (95% CI: 5.0–6.5) for the Pom‐based group, 10.5 months (5.2–15.8) for the Dara‐based group, and 6.7 months (4.0–9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara‐based vs. Pom‐based, DPd vs. Pom‐based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double‐refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara‐based regimens over Pom‐based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara‐based and DPd regimens (Pom‐based 39.6% vs. Dara‐based 64.7% vs. DPd 70.8%, p = 0.009). Conclusions: In real‐world settings, Pom‐based, Dara‐based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara‐based therapy yielded superior clinical response and PFS compared to Pom‐based therapy. [ABSTRACT FROM AUTHOR]

Daratumumab injection was approved by China in 2019 for the treatment of recurrent or refractory multiple myeloma. However, the molecular weight of daratumumab, an immunoglobin G1 kappa human monoclonal antibody, was similar to that of M protein and could not be distinguished from IgG κ M protein in SPEP and SIFE. It might lead to false-positive detection resulting in misdiagnose and confusing evaluation of therapeutic response, especially for patients with IgG κ M proteins. Herein, we reported two cases encountered in our daily clinical work. These two case reports could serve as a reminder to global hematologists who have not yet started or just begun to use the drug of daratumumab. [ABSTRACT FROM AUTHOR]

Introduction: The ALCYONE trial found that daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) can significantly improve progression-free survival (PFS) and overall survival (OS) for patients with transplant-ineligible, newly diagnosed multiple myeloma (MM) in China. In the present study, we evaluated the cost-effectiveness of D-VMP versus VMP for patients with newly diagnosed MM in China.Methods: A Markov model was used to estimate the cost-effectiveness of frontline D-VMP versus VMP for MM. The life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed to assess the robustness of the model and address uncertainties in variable estimates. Subgroup analysis was also performed.Results: D-VMP provided an additional 2.99 LYs and 1.67 QALYs compared with VMP, with incremental $64,920 per LY and $116,015 per QALY gained. The results of the univariable sensitivity analysis showed that the parameter that had the greatest impact on the ICER was the cost of subsequent treatment and daratumumab. When the cost of daratumumab was 100%, 70%, 50%, and 30% of the current price, the probability of D-VMP being cost-effective was 2.49%, 16.11%, 39.09%, and 70.73% at the willingness-to-pay (WTP) threshold of $30,950/QALY, respectively. The results demonstrated that the ICER in all subgroups remained > $30,950/QALY.Conclusion: D-VMP versus VMP is likely to exceed the commonly accepted values of cost-effectiveness in patients with transplant-ineligible, newly diagnosed MM in China. [ABSTRACT FROM AUTHOR]

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.