Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

Ha, Liebman; Mn, Saleh; Jb, Bussel; Og, Negrea; Horne, Heather; Wa, Wegener; Dm, Goldenberg

doi:10.3324/haematol.2016.146738

Cited by 9 publications

(12 citation statements)

References 24 publications

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“…Our preliminary data also showed that the response and mortalities did not correlated with icaritin dosages of 600 vs. 800 mg b.i.d. (Additional file 6: Table S1 and Additional file 7: Figure S3), which was consistent with the observations in other immune oncology trials [24, 25].…”

Section: Discussionsupporting

confidence: 90%

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers

Fan

Li²,

Ding

et al. 2019

BMC Cancer

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Background With poor prognosis and limited treatment options for advanced hepatocellular carcinoma (HCC), development of novel therapeutic agents is urgently needed. This single-arm phase I study sought to assess the safety and preliminary efficacy of icaritin in human as a potential oral immunotherapy in addition to the immune-checkpoint inhibitors. Methods Eligible advanced HCC patients with Child-Pugh Class A or B were administered with a fixed oral dose of icaritin at either 600 or 800 mg b.i.d. The primary endpoint was safety, and the secondary endpoints included time-to-progression (TTP), overall survival (OS) and the clinical benefit rate (CBR). Icaritin treatment induced immune biomarkers and immune-modulating activities in myeloid cells were also explored. Results No drug-related adverse events ≥ Grade 3 were observed in all 20 enrolled HCC patients. Among the 15 evaluable patients, 7 (46.7%) achieved clinical benefit, representing one partial response (PR, 6.7%) and 6 stable disease (SD, 40%). The median TTP was 141 days (range: 20-343 days), and the median OS was 192 days (range: 33-1036 days). Durable survival was observed in PR/SD patients with a median OS of 488 days (range: 72-773). TTP was significantly associated with the dynamic changes of peripheral neutrophils ( p = 0.0067) and lymphocytes ( p = 0.0337). Icaritin treatment induced changes in immune biomarkers-and immune-suppressive myeloid cells were observed. Conclusions Icaritin demonstrated safety profiles and preliminary durable survival benefits in advanced HCC patients, which were correlated with its immune-modulation activities and immune biomarkers. These results suggested the potential of icaritin as a novel oral immunotherapy for advanced HCC in addition to antibody-based PD-1/PD-L1 blockade therapies. Trial registration Clinicaltrial.gov identifier. NCT02496949 (retrospectively registered, July 14, 2015). Electronic supplementary material The online version of this article (10.1186/s12885-019-5471-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers

Fan

Li²,

Ding

et al. 2019

BMC Cancer

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“…In 1 study of humans with ITP, the IBLS was reported to be associated with platelet count, but this association did not persist for patients with platelet counts < 30,000/μL, likely because of the heterogeneity in clinical bleeding seen with severe thrombocytopenia. Since the initial description of the IBLS, several other publications in the human literature have implemented this bleeding score in ITP patients to make correlations between clinical bleeding severity and clinicopathologic variables and to assess clinical bleeding in treatment trials …”

Section: Discussionmentioning

confidence: 99%

“…Since the initial description of the IBLS, several other publications in the human literature have implemented this bleeding score in ITP patients to make correlations between clinical bleeding severity and clinicopathologic variables [24][25][26] and to assess clinical bleeding in treatment trials. 27,28 Although similar to the IBLS, several modifications tailor the DOGi- The training module instructed users on implementation of the DOGiBAT scoring tool. To evaluate the effects of training, veterinary students were utilized as a large population of individuals who likely had less clinical experience than the clinicians in phase 1.…”

Section: The Correlation Between Outcome Measures and Dogibat Andmentioning

confidence: 99%

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs

Makielski

Brooks

Wang

et al. 2018

Veterinary Internal Medicne

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BackgroundA method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials.Hypothesis/ObjectivesTo develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation.AnimalsClient‐owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non‐ITP.MethodsA novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs.ResultsClinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (r s = −0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (r s = 0.512, P < .0001) and hospitalization duration (r s = 0.35, P = .006).Conclusions and Clinical ImportanceThe DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials.

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“…Despite its good tolerance and efficiency, veltuzumab is not routinely used in clinical practice. 94 Obinutuzumab has also been engineered to increase its cytotoxicity and B-cell depletion in hematological B-cell malignancies. Whether this amelioration is of interest in ITP to increase response rates or response duration has not yet been investigated.…”

Section: Future Therapeutic Perspectivesmentioning

confidence: 99%

Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments

et al. 2021

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Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells by their antigen-presenting functions. Moreover, the activation of the classical complement pathway participates to platelet opsonization and also to their destruction by complement-dependent cytotoxicity. Platelet destruction is also mediated by a FcγR-independent pathway, involving platelet desialylation that favors their binding to the Ashwell-Morell receptor and their clearance in the liver. Cytotoxic T cells also contribute to ITP pathogenesis by mediating cytotoxicity against megakaryocytes and peripheral platelets. The deficient megakaryopoiesis resulting from both the humoral and the cytotoxic immune responses is sustained by inappropriate levels of thrombopoietin, the major growth factor of megakaryocytes. The better understanding of ITP pathogenesis has provided important therapeutic advances. B cell-targeting therapies and thrombopoietin-receptor agonists (TPO-RAs) have been used for years. New emerging therapeutic strategies that inhibit FcγR signaling, the neonatal Fc receptor or the classical complement pathway, will deeply modify the management of ITP in the near future.

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Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

Cited by 9 publications

References 24 publications

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs

Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments

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