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JAMA Dermatology Dec 2014IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse,...
IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse, and intravenous rituximab infusions are expensive. Therefore, cost-effective anti-CD20 therapies are desirable.OBSERVATIONS A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second-generation humanized anti-CD20 antibody, to a patient with refractory PV. Veltuzumab was administered as two 320-mg (188mg/m2) subcutaneous doses 2 weeks apart, resulting in complete remission of disease off therapy. The disease relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab, using the same dosage regimen, again induced complete remission off therapy, which remained at9 months. No serious adverse events occurred during 35 months of follow-up. Serum veltuzumab levels were 22 and 29 μg/mL 2 weeks after the first dose of each cycle, and the drug remained detectable in the serum for longer than 3 months. Relapse and response to veltuzumab generally correlated with desmoglein 3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that occurred after a long-term remission, the patient demonstrated an elevated naive (CD19+CD27−) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional (CD19+CD24+CD38+) B-cell frequency of 12.5%.CONCLUSIONS AND RELEVANCE Subcutaneous veltuzumab may be a safe, effective, and more economical alternative to intravenous rituximab for PV therapy. Clinical trials of subcutaneous veltuzumab for PV are warranted.
Topics: Adult; Antibodies, Monoclonal, Humanized; Female; Humans; Immunologic Factors; Injections, Subcutaneous; Pemphigus; Recurrence; Remission Induction; Retreatment
PubMed: 25133328
DOI: 10.1001/jamadermatol.2014.1939 -
Blood Reviews Sep 2017The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and... (Review)
Review
The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting. We review the current status of these antibodies, and discuss how their mechanisms of action may impact on the choice of combinations with novel small molecule agents.
Topics: Antigens, CD20; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Discovery; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Molecular Targeted Therapy; Rituximab; Treatment Outcome
PubMed: 28499646
DOI: 10.1016/j.blre.2017.05.002 -
Auto- Immunity Highlights Nov 2017The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several...
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab. We conducted a literature search of relevant randomized clinical trials in the PubMed database and ongoing trials in Clinicaltrials.gov. Most of these trials have evaluated intravenous ocrelizumab or subcutaneous ofatumumab in rheumatoid arthritis, multiple sclerosis, or systemic lupus erythematosus. Understanding how newer anti-CD20 mAbs compare with rituximab in terms of efficacy, safety, convenience, and cost is important for guiding future management of anti-CD20 mAb therapy in autoimmune diseases.
PubMed: 29143151
DOI: 10.1007/s13317-017-0100-y -
Expert Review of Hematology Dec 2014Anti-CD20 monoclonal antibodies (mAbs), rituximab, ofatumumab and obinutuzumab, have a significant impact in the treatment of chronic lymphocytic leukemia (CLL),... (Review)
Review
Anti-CD20 monoclonal antibodies (mAbs), rituximab, ofatumumab and obinutuzumab, have a significant impact in the treatment of chronic lymphocytic leukemia (CLL), particularly in combination with chemotherapy. Over the last few years, several new mAbs have been developed and investigated in CLL. The most promising newer mAbs are directed against CD20, CD19, CD37 and CD40. Combinations of antibodies with targeted drugs like ibrutinib, idelalisib or lenalidomide will probably replace chemotherapy-based combinations in the near future. This review gives a critical overview of established mAbs as well as new antibodies potentially useful in CLL.
Topics: Animals; Antibodies, Monoclonal; Antigens, CD19; Antigens, CD20; Antigens, Neoplasm; CD40 Antigens; Humans; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Tetraspanins
PubMed: 25249370
DOI: 10.1586/17474086.2014.963048 -
Indian Journal of Dermatology 2017Therapeutics of autoimmune bullous disease has seen a major shift of focus from more global immunosuppression to targeted immunotherapy. Anti CD 20 monoclonal antibody...
Therapeutics of autoimmune bullous disease has seen a major shift of focus from more global immunosuppression to targeted immunotherapy. Anti CD 20 monoclonal antibody Rituximab revolutionized the therapeutics of autoimmune bullous disease particularly pemphigus. Though it is still being practiced off-label, evidences in the form of RCT and meta analysis are now available. Other novel anti CD 20 monoclonal antibodies like ofatumumab, veltuzumab, and ocrelizumab, tositumomab or obinutuzumab/GA101 may add to the therapeutic options in coming days. Beyond anti CD 20 monoclonal antibodies other options that show promise at least in select scenario are omalizumab, TNF inhibitors plasmapheresis and intravenous immunoglobulin. The present article will discuss the role of rituximab and other newer therapeutics in the treatment of autoimmune blistering disease, especially pemphigus and suggests their positions in the therapeutic ladder.
PubMed: 28584371
DOI: 10.4103/ijd.IJD_199_17 -
Haematologica Nov 2014A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead...
A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Marrow; Disease Progression; Female; Humans; Indium Radioisotopes; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Radioimmunotherapy; Tomography, X-Ray Computed; Treatment Outcome; Yttrium Radioisotopes
PubMed: 25150258
DOI: 10.3324/haematol.2014.112110 -
Haematologica Nov 2016We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with... (Comparative Study)
Comparative Study
We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×10/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×10/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×10/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066.
Topics: Antibodies, Monoclonal, Humanized; Antibody Formation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Count; Recurrence; Remission Induction; Thrombocytopenia
PubMed: 27515248
DOI: 10.3324/haematol.2016.146738 -
Leukemia & Lymphoma 2016To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or...
To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or 320 mg injections every 2 weeks × 4 doses (n = 11) or 160 or 320 mg twice-weekly × 16 doses (n = 10). Treatment was well tolerated with only occasional, mild-moderate, transient injection reactions. Lymphocytosis decreased in all patients (maximum decrease, 5-91%), with 12 patients obtaining >50% decreases. Of 14 patients with lymphadenopathy on CT imaging, 5 (36%) achieved 14-61% reductions (sum of perpendicular diameters). By NCI-WG criteria, two patients achieved partial responses (10%). SC veltuzumab appeared active in all dose groups, with no obvious exposure-response relationship, despite cumulative doses ranging from 320-5120 mg. Overall median progression-free survival was 7.7 months; three patients remained progression-free >1 year (2 ongoing at 2-year study completion). These data suggest further studies of SC veltuzumab in CLL are warranted.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Drug Monitoring; Female; Humans; Injections, Subcutaneous; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Retreatment; Treatment Outcome
PubMed: 26389849
DOI: 10.3109/10428194.2015.1085531 -
Journal of Clinical Immunology Aug 2021
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Chromosomes, Human, Pair 6; Female; Gene Deletion; Haploinsufficiency; Hereditary Autoinflammatory Diseases; Humans; Tumor Necrosis Factor alpha-Induced Protein 3
PubMed: 34032947
DOI: 10.1007/s10875-021-01048-w