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David M Goldenberg - One of the best experts on this subject based on the ideXlab platform.

  • the mechanistic impact of cd22 engagement with Epratuzumab on b cell function implications for the treatment of systemic lupus erythematosus
    Autoimmunity Reviews, 2015
    Co-Authors: Thomas Dorner, David M Goldenberg, Anthony Shock, Peter E Lipsky
    Abstract:

    Abstract Epratuzumab is a B-cell-directed non-depleting monoclonal antibody that targets CD22. It is currently being evaluated in two phase 3 clinical trials in patients with systemic lupus erythematosus (SLE), a disease associated with abnormalities in B-cell function and activation. The mechanism of action of Epratuzumab involves perturbation of the B-cell receptor (BCR) signalling complex and intensification of the normal inhibitory role of CD22 on the BCR, leading to reduced signalling and diminished activation of B cells. Such effects may result from down-modulation of CD22 upon binding by Epratuzumab, as well as decreased expression of other proteins involved in amplifying BCR signalling capability, notably CD19. The net result is blunting the capacity of antigen engagement to induce B-cell activation. The functional consequences of Epratuzumab binding to CD22 include diminished B-cell proliferation, effects on adhesion molecule expression, and B-cell migration, as well as reduced production of pro-inflammatory cytokines, such as IL-6 and TNF. Studies in patients treated with Epratuzumab have revealed a number of pharmacodynamic effects that are linked to the mechanism of action (i.e., a loss of the target molecule CD22 from the B-cell surface followed by a modest reduction in peripheral B-cell numbers after prolonged therapy). Together, these data indicate that Epratuzumab therapy affords a unique means to modulate BCR complex expression and signalling.

  • re induction chemoimmunotherapy with Epratuzumab in relapsed acute lymphoblastic leukemia all phase ii results from children s oncology group cog study advl04p2
    Pediatric Blood & Cancer, 2015
    Co-Authors: Elizabeth A Raetz, David M Goldenberg, Mitchell S Cairo, Michael J Borowitz, Xiaomin Lu, Meenakshi Devidas, Joel M Reid, William A Wegener, Hui Zeng, James A Whitlock
    Abstract:

    Background Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of Epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. Procedure Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m2/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. Results CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without Epratuzumab. Rates of MRD negativity (<0.01%) were 31% in B1 (P = 0.4128) and 39% in B2 patients (P = 0.1731), compared to 25% in historical controls. The addition of Epratuzumab was well tolerated, with a similar toxicity profile to that observed with the re-induction chemotherapy platform regimen alone. Conclusions Epratuzumab was well tolerated in combination with re-induction chemotherapy. While CR2 rates were not improved compared to historical controls treated with chemotherapy alone, there was a non-significant trend towards improvement in MRD response with the addition of Epratuzumab (twice weekly for eight doses) to re-induction chemotherapy. Pediatr Blood Cancer 2015;62:1171–1175. © 2015 Wiley Periodicals, Inc.

  • Re-induction chemoimmunotherapy with Epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2.
    Pediatric Blood & Cancer, 2015
    Co-Authors: Elizabeth A Raetz, David M Goldenberg, Mitchell S Cairo, Michael J Borowitz, Xiaomin Lu, Meenakshi Devidas, Joel M Reid, William A Wegener, Hui Zeng, James A Whitlock
    Abstract:

    Background Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of Epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. Procedure Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m2/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. Results CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without Epratuzumab. Rates of MRD negativity (

  • extensive crosslinking of cd22 by Epratuzumab triggers bcr signaling and caspase dependent apoptosis in human lymphoma cells
    mAbs, 2015
    Co-Authors: Chien-hsing Chang, Yang Wang, Pankaj Gupta, David M Goldenberg
    Abstract:

    Epratuzumab has demonstrated therapeutic activity in patients with non-Hodgkin lymphoma, acute lymphoblastic leukemia, systemic lupus erythematosus, and Sjogren's syndrome, but its mechanism of affecting normal and malignant B cells remains incompletely understood. We reported previously that Epratuzumab displayed in vitro cytotoxicity to CD22-expressing Burkitt lymphoma cell lines (Daudi and Ramos) only when immobilized on plates or combined with a crosslinking antibody plus a suboptimal amount of anti-IgM (1 μg/mL). Herein, we show that, in the absence of additional anti-IgM ligation, extensive crosslinking of CD22 by plate-immobilized Epratuzumab induced intracellular changes in Daudi cells similar to ligating B-cell antigen receptor with a sufficiently high amount of anti-IgM (10 μg/mL). Specifically, either treatment led to phosphorylation of CD22, CD79a and CD79b, along with their translocation to lipid rafts, both of which were essential for effecting caspase-dependent apoptosis. Moreover, such imm...

  • anti cd22 90y Epratuzumab tetraxetan combined with anti cd20 veltuzumab a phase i study in patients with relapsed refractory aggressive non hodgkin lymphoma
    Haematologica, 2014
    Co-Authors: Thomas E Witzig, Robert M Sharkey, William A Wegener, Michael B Tomblyn, Jamal Misleh, David M Goldenberg
    Abstract:

    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 90Y-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/m2 veltuzumab once-weekly for 4 weeks, with 90Y-Epratuzumab tetraxetan at planned doses in weeks 3 and 4, and 111In-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. 111In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For 90Y-Epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m2 (222 MBq/m2) × 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 90Y 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 90Y-Epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.

William A Wegener - One of the best experts on this subject based on the ideXlab platform.

  • re induction chemoimmunotherapy with Epratuzumab in relapsed acute lymphoblastic leukemia all phase ii results from children s oncology group cog study advl04p2
    Pediatric Blood & Cancer, 2015
    Co-Authors: Elizabeth A Raetz, David M Goldenberg, Mitchell S Cairo, Michael J Borowitz, Xiaomin Lu, Meenakshi Devidas, Joel M Reid, William A Wegener, Hui Zeng, James A Whitlock
    Abstract:

    Background Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of Epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. Procedure Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m2/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. Results CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without Epratuzumab. Rates of MRD negativity (<0.01%) were 31% in B1 (P = 0.4128) and 39% in B2 patients (P = 0.1731), compared to 25% in historical controls. The addition of Epratuzumab was well tolerated, with a similar toxicity profile to that observed with the re-induction chemotherapy platform regimen alone. Conclusions Epratuzumab was well tolerated in combination with re-induction chemotherapy. While CR2 rates were not improved compared to historical controls treated with chemotherapy alone, there was a non-significant trend towards improvement in MRD response with the addition of Epratuzumab (twice weekly for eight doses) to re-induction chemotherapy. Pediatr Blood Cancer 2015;62:1171–1175. © 2015 Wiley Periodicals, Inc.

  • Re-induction chemoimmunotherapy with Epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2.
    Pediatric Blood & Cancer, 2015
    Co-Authors: Elizabeth A Raetz, David M Goldenberg, Mitchell S Cairo, Michael J Borowitz, Xiaomin Lu, Meenakshi Devidas, Joel M Reid, William A Wegener, Hui Zeng, James A Whitlock
    Abstract:

    Background Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of Epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse. Procedure Therapy consisted of three established blocks of re-induction chemotherapy. Epratuzumab (360 mg/m2/dose) was combined with chemotherapy on weekly × 4 (B1) and twice weekly × 4 [eight doses] (B2) schedules during the first re-induction block. Remission rates and minimal residual disease (MRD) status were compared to historical rates observed with the identical chemotherapy platform alone. Results CR2 was achieved in 65 and 66%, of the evaluable B1 (n = 54) and B2 patients (n = 60), respectively; unchanged from that observed historically without Epratuzumab. Rates of MRD negativity (

  • anti cd22 90y Epratuzumab tetraxetan combined with anti cd20 veltuzumab a phase i study in patients with relapsed refractory aggressive non hodgkin lymphoma
    Haematologica, 2014
    Co-Authors: Thomas E Witzig, Robert M Sharkey, William A Wegener, Michael B Tomblyn, Jamal Misleh, David M Goldenberg
    Abstract:

    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 90Y-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/m2 veltuzumab once-weekly for 4 weeks, with 90Y-Epratuzumab tetraxetan at planned doses in weeks 3 and 4, and 111In-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. 111In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For 90Y-Epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m2 (222 MBq/m2) × 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 90Y 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 90Y-Epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.

  • Epratuzumab for patients with moderate to severe flaring sle health related quality of life outcomes and corticosteroid use in the randomized controlled alleviate trials and extension study sl0006
    Rheumatology, 2014
    Co-Authors: Vibeke Strand, Daniel J. Wallace, William A Wegener, Caroline Gordon, Kathryn Hobbs, Michelle Petri, Kenneth C Kalunian, Lexy Kelley, B Kilgallen, David M Goldenberg
    Abstract:

    Objective. To evaluate health-related quality of life (HRQOL) and corticosteroid use in patients with moderate to severely active SLE enrolled in two international, multicentre, randomized controlled trials of Epratuzumab (ALLEVIATE-1 and -2) and a long-term extension study (SL0006). Methods. Ninety ALLEVIATE patients (43% BILAG A, mean BILAG score 13.2) were randomized to receive 360 mg/m 2 (n = 42) or 720 mg/m 2 (n = 11) Epratuzumab or placebo (n = 37), plus standard of care, in 12-week cycles. Corticosteroid use, patient and physician global assessments of disease activity (PtGA and PGA) and 36-item Medical Outcomes Survey Short Form (SF-36) results were recorded at baseline and every 4 weeks. Both trials were prematurely discontinued due to a drug supply interruption; patients followed for 56 months were analysed. Twenty-nine patients continued in SL0006, with interim analysis at a median exposure of 120 (range 13184) weeks. Results. At week 12, proportions of patients with a PGA 520% above baseline or with a PtGA improvement greater than or equal to the minimum clinically important difference were higher in the Epratuzumab arms than the placebo arm. PGA and PtGA improvements were sustained but did not reach statistical significance. At week 24, mean cumulative corticosteroid doses with Epratuzumab 360 and 720 mg/m 2 were 1051 and 1973 mg less than placebo (P = 0.034 and 0.081, respectively). At week 48, SF-36 scores approached or exceeded US age- and gender-matched norms in five domains with the 360 mg/m 2 treatment. Improvements were maintained in SL0006 over 2 years.

  • bcr abl1 molecular remission after 90y Epratuzumab tetraxetan radioimmunotherapy in cd22 ph b all proof of principle
    European Journal of Haematology, 2013
    Co-Authors: Patrice Chevallier, Caroline Bodetmilin, T Eugene, Nelly Robillard, Martine Escoffrebarbe, Audrey Menard, Claire Le Houerou, T Guillaume, J Delaunay, William A Wegener
    Abstract:

    Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy (RAIT) in B-acute lymphoblastic leukemia (ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome-positive B-ALL in third relapse who received RAIT with 90yttrium (90Y)-labeled anti-CD22 Epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR-ABL1 molecular remission documented by RT-qPCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. 90Y-Epratuzumab tetraxetan may be a promising therapeutic option for CD22+ B-ALL patients.

Patrice Chevallier - One of the best experts on this subject based on the ideXlab platform.

  • hyper cvad Epratuzumab as a salvage regimen for younger patients with relapsed refractory cd22 positive precursor b cell acute lymphocytic leukemia
    Haematologica, 2017
    Co-Authors: Patrice Chevallier, Francoise Isnard, Francoise Huguet, Emmanuel Raffoux, Thibaut Leguay, Aude Charbonnier, Sylvain Chantepie, Xavier Thomas, Tony Marchand, Sebastien Maury
    Abstract:

    We investigated whether combining hyper-CVAD and Epratuzumab, a humanized monoclonal therapeutic antibody against CD22, in very high-risk younger adults with relapsed/refractory CD22+ precursor B-cell acute lymphocytic leukemia could improve the response of patients. The overall response rate was 50

  • Hyper-CVAD + Epratuzumab as a salvage regimen for younger patients with relapsed/refractory CD22-positive precursor B-cell acute lymphocytic leukemia.
    Haematologica, 2017
    Co-Authors: Patrice Chevallier, Francoise Isnard, Francoise Huguet, Emmanuel Raffoux, Thibaut Leguay, Aude Charbonnier, Sylvain Chantepie, Xavier Thomas, Tony Marchand, Sebastien Maury
    Abstract:

    We investigated whether combining hyper-CVAD and Epratuzumab, a humanized monoclonal therapeutic antibody against CD22, in very high-risk younger adults with relapsed/refractory CD22+ precursor B-cell acute lymphocytic leukemia could improve the response of patients. The overall response rate was 50

  • Hyper-CVAD Plus Epratuzumab As Salvage Regimen for Younger Relapsed/Refractory CD22+ B Acute Lymphoblastic Leukemia (ALL) Patients: Results of the Phase 2 Prospective Cheprall Study
    Blood, 2016
    Co-Authors: Patrice Chevallier, Francoise Isnard, Francoise Huguet, Emmanuel Raffoux, Thibaut Leguay, Aude Charbonnier, Sylvain Chantepie, Xavier Thomas, Tony Marchand, Sebastien Maury
    Abstract:

    Abstract Purpose: Hyper-CVAD developed by the MD Anderson group a few years ago, is one of the standard salvage regimen used for younger relapsed/refractory ALL patients. Recently, targeted therapies using monoclonal antibodies directed against such surface antigens as CD19, CD20 or CD22 have allowed to obtain complete remission (CR) in B ALL expressing these markers. We hypothesized that combining Hyper-CVAD and an anti-CD22 monoclonal antibody could improve the response of such patients. Materials and Methods: This study evaluated the Cheprall salvage regimen, where Epratuzumab, a humanized therapeutic monoclonal antibody against CD22 with mainly ADCC property, was associated to Hyper-CVAD, in younger patients (18-59 years old) with relapsed/refractory CD22+ (>30% of expression) B-ALL. Cheprall consisted of Epratuzumab 360 mg/m²/d iv on days 1, 8, 15 and 22, cyclophosphamide 300 mg/m²/12h iv on days 1 to 3, vincristine 2 mg iv on days +4 and +11, doxorubicin 50 mg/m² iv on day +4 and dexamethasone 40 mg po on days 1 to 4 and 11 to 14. The main objective of the study was the overall response rate (CR + CR with incomplete platelets recovery (<100 000/mm3, CRp) + partial response (PR, >=50% of bone marrow (BM) blasts decrease or CR with persistent extramedulladory disease) evaluated between 4 and 6 weeks from day+1. Secondary objectives were overall (OS) and leukemia free (LFS) survivals and minimal residual disease (MRD) evaluated by flow cytometry. Results: Between January 2011 and April 2016, 31 patients from 11 French centres were enrolled in the study. A combination of Epratuzumab + vincristine and dexamethasone (EVD) only was given to one patient subsequently excluded from the analysis. Among the 30 patients ultimately considered for analyses, 19 were males and the median age was 35 years (range: 21-59). The median time between diagnosis and Cheprall was 14.5 months (range: 4-130) and 13 patients had been allotransplanted. Disease status at time of Cheprall was as follows: primary refractory n=3; first relapse non treated n=13; refractory first relapse n=6, second relapse non treated n=7 and fourth relapse n=1. Median percentage of white blood cells and BM blasts were 4525/mm3(range: 90-86790) and 60% (range: 15-100), respectively. The median CD22 expression of BM blasts was 100% (range: 36-100). Four patients had extramedullary disease: breast n=2, parotid n=1, nervous central system n=1 (deviation). Cheprall was overall well tolerated including mostly pancytopenia as grade ¾ toxicities. Three patients died during aplasia (septis n=1; cerebral haemorrhage n=1, fusariosis n=1) and were not evaluable for response. The overall response rate was 50% (n=15) including 9 CR (30%), 1 CRp (3%) and 5 PR (17%). The number of CR/CRp was higher for patients in first non-treated relapse (54% vs 18%) with an age below 36 years (50% vs 14%), with <=50% of BM blasts (57% vs 26%) and with a delay between diagnosis and Cheprall > 18 months (54% vs 17%). Four out of 9 evaluated CR/CRp patients (45%) were documented with negative MRD. All patients in CR/CRp and 1 patient in PR received a consolidation consisting of a second cycle of Cheprall n=5, EVD n=5 or blinatumomab n=1. At the time of analysis (July 2016), all patients have died (during aplasia n=3, progression n=23, multiple organ failure n=1), except three responders still in CR, but yet recently enrolled (2015 n=1, 2016 n=2). Six patients received allogeneic transplant after Cheprall: 4 in CR2, 1 as salvage treatment and 1 in CR3. The last patient included and who achieved CR2 should be allografted in August 2016. Median OS was 3 months (range: 0.2-34.8). Median LFS for those achieving CR/CRp was 4.5 months (range: 1-12). Conclusion: Hyper-CVAD + Epratuzumab allowed to obtain 50% of response in this cohort of patients at high risk of failure with refractory/relapsed younger CD22+ B-ALL. Disease improvement was however short-lived, which could be explained either by an insufficient disease load decrease and/or by escape of the blast cells to Epratuzumab. This partial efficacy in a population of poor prognosis may suggest that Epratuzumab should be tested within first-line chemotherapies as it may participate to decrease MRD level, especially before transplantation. The trial was registered at http://clinicaltrials.gov/ct no.NCT01219816. This study was supported by a grant from the French National Cancer Institute (PHRC 2010). Disclosures Huguet: Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Thomas:Pfizer: Consultancy. Goldenberg:Immunomedics: Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Wegener:Immunomedics: Employment, Honoraria.

  • 90y labelled anti cd22 Epratuzumab tetraxetan in adults with refractory or relapsed cd22 positive b cell acute lymphoblastic leukaemia a phase 1 dose escalation study
    The Lancet Haematology, 2015
    Co-Authors: Patrice Chevallier, T Eugene, Nelly Robillard, Francoise Isnard, Franck E Nicolini, Martine Escoffrebarbe, Francoise Huguet, Mathilde Hunault, Antoine Marcais, Joelle Gaschet
    Abstract:

    Summary Background Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 Epratuzumab tetraxetan ( 90 Y-DOTA-Epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study. Methods Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of 90 Y-DOTA-Epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m 2 (92·5 MBq/m 2 ; level 1), 5·0 mCi/m 2 (185 MBq/m 2 ; level 2), 7·5 mCi/m 2 (277·5 MBq/m 2 ; level 3), and 10·0 mCi/m 2 (370 MBq/m 2 ; level 4). The primary objective was to identify the maximum tolerated dose of 90 Y-DOTA-Epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457. Findings Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27–77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3–4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4). Interpretation 90 Y-DOTA-Epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m 2 1 week apart per cycle for phase 2 studies. Funding Immunomedics and Direction de la Recherche Clinique of Nantes.

  • vincristine dexamethasone and Epratuzumab for older relapsed refractory cd22 b acute lymphoblastic leukemia patients a phase ii study
    Haematologica, 2015
    Co-Authors: Patrice Chevallier, Nelly Robillard, Francoise Isnard, Francoise Huguet, J Delaunay, Emmanuel Raffoux, Anne Etienne, Thibaut Leguay, Thierry Guillaume, Aude Charbonnier
    Abstract:

    The treatment of older patients with acute lymphoblastic leukemia (ALL) still represents an unmet medical need. Here we report the results of a chemoimmunotherapy approach combining vincristine/dexamethasone and Epratuzumab, a humanized monoclonal therapeutic antibody against CD22, in patients over

Daniel J. Wallace - One of the best experts on this subject based on the ideXlab platform.

  • THU0286 Immunologic Response to Long-Term Epratuzumab Treatment in Sl0008, An Open-Label Long-Term Extension Study in Patients with Moderate-to-Severe Systemic Lupus Erythematosus
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Vibeke Strand, Daniel J. Wallace, B Kilgallen, S Bongardt, Piotr Leszczyński, Mauro Waldemar Keiserman, Caroline Gordon
    Abstract:

    Background Epratuzumab is a monoclonal antibody targeting CD22 that may affect B-cell signaling, adhesion and migration.[1][1],[2][2] We report immunologic response in SL0008 ([NCT00660881][3]), an open-label extension of EMBLEM™, a 12-week phase IIb study in moderate-to-severe SLE patients. Objectives To assess the effect of long-term Epratuzumab treatment on B cells and other immune parameters. Methods EMBLEMTM patients who completed 12 weeks of blinded treatment and patients who discontinued due to lack of efficacy but completed ≥8 weeks were eligible for SL0008. Patients received 1200 mg Epratuzumab at weeks 0 and 2 of repeating 12-week cycles. Immune assessments included B-cell (CD20+) and T-cell (CD3+) counts, and immunoglobulin levels. B-cell surface CD22 levels are given as mean fluorescence intensity (MFI). Results SL0008 recruited 203 patients aged 18–68 years (mean 39 years; 95% female; 78% Caucasian). Median (range) Epratuzumab exposure was 845 (75–1185) days. Median absolute B-cell counts decreased, plateauing at median (range) 50% (–94 to 286) below EMBLEMTM baseline at week 112, the last timepoint at which >50% of patients reported this endpoint (Table). CD22 expression on all B cell subsets (median MFI) remained low relative to EMBLEMTM baseline throughout SL0008. No consistent trends were seen in median absolute T-cell counts, which remained similar to EMBLEMTM baseline (3.0% [range –74 to 1608] higher at week 112). No consistent trends were observed for IgA and IgG levels but IgM levels decreased slightly (–0.21 g/L by week 112). At week 48 (including last visit data if week 48 unavailable), mean total BILAG (n=195) was 13.9 for patients with screening B-cell count

  • AB0633 Epratuzumab-treated SLE patients report improvements in health-related quality of life: Interim results from a us open-label extension study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Vibeke Strand, Daniel J. Wallace, Kathryn Hobbs, Kenneth C Kalunian, B Kilgallen, E. Nikaï, W. Wegener
    Abstract:

    Background Epratuzumab, an anti-CD22 monoclonal antibody, is in development for the treatment of systemic lupus erythematosis (SLE). SL0006 is an ongoing, open-label extension study following the randomized double blind ALLEVIATE trials, which were prematurely terminated due to interruption of drug supply.1Assessment of health-related quality of life (HRQoL) alongside measures of disease activity and damage provides a more comprehensive view of therapeutic responses,2 and is recommended in SLE clinical trials.3 Objectives To assess the effect of Epratuzumab on HRQoL in SL0006 using SF-36. Methods All patients enrolled in ALLEVIATE US sites who received randomized treatment (n=60) were eligible for enrolment in SL0006, subject to physician judgment. Twenty-nine patients (90% female, 79% Caucasian, mean age 40 years) entered SL0006, having received placebo (n=8), 360 (n=17) or 720 (n=4) mg/m2 Epratuzumab during ALLEVIATE. In SL0006, all patients received 12-week cycles of 360 mg/m2 Epratuzumab; two infusions on weeks 0 and 1 of each cycle. SF-36 was assessed at screening and every 4 weeks thereafter. This interim analysis extends through 31 Dec 2009, representing a median 120 weeks (range 13–184) of exposure. Data are summarized using descriptive statistics. Results At ALLEVIATE baseline, SF-36 domain scores were 7.9–48.5 points lower than for age- and gender-matched norms, reflecting the broad impact of active SLE on HRQoL. In ALLEVIATE, patients reported improvements ≥ minimum clinically important differences (MCID) in physical summary (PCS) and four physical SF-36 domain scores. Further improvement in HRQoL was evident early in SL0006 (week 4), and sustained through weeks 44–48 of treatment ([Table 1][1]). Scores stabilized during the 2ndyear; further improvements were reported at weeks 96–100, after which numbers of patients were small (n

  • efficacy and safety of Epratuzumab in moderately to severely active systemic lupus erythematosus results from two phase iii randomized double blind placebo controlled trials
    Arthritis & Rheumatism, 2017
    Co-Authors: Megan E B Clowse, Daniel J. Wallace, Kathryn Hobbs, Michelle Petri, Richard Furie, Marilyn C Pike, Piotr Leszczynski, Michael C Neuwelt, M Keiserman, Liliana Duca
    Abstract:

    Objective Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of Epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, Epratuzumab 600 mg every week, or Epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results In the EMBODY 1 and EMBODY 2 trials of Epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the Epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. Conclusion In patients with moderate or severely active SLE, treatment with Epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

  • efficacy and safety of Epratuzumab in moderately to severely active systemic lupus erythematosus results from the phase 3 randomized double blind placebo controlled trials embody 1 and embody 2
    Arthritis & Rheumatism, 2016
    Co-Authors: Megan E B Clowse, Daniel J. Wallace, Kathryn Hobbs, Michelle Petri, Richard Furie, Marilyn C Pike, Piotr Leszczynski, Michael C Neuwelt, M Keiserman, Liliana Duca
    Abstract:

    Objective Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in B cells. We report data from two Phase 3, randomized, double-blind, placebo-controlled studies of Epratuzumab in patients with moderately to severely active SLE; EMBODY 1 (NCT01262365) and EMBODY 2 (NCT01261793). Methods Patients met ≥4 ACR revised criteria, were ANA and/or anti-dsDNA positive, had SLEDAI-2K score ≥6, BILAG-2004 ≥1 A or ≥2 Bs in mucocutaneous, musculoskeletal or cardiorespiratory domains, and were receiving standard therapy (ST) including mandatory corticosteroids (5–60 mg/day). BILAG A grade renal and central nervous system domain scores were excluded. Patients were randomized 1:1:1 to placebo, Epratuzumab 600 mg every week (QW) or 1200 mg every other week (QOW), with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all three dosing arms continued their ST. The primary endpoint was the Week 48 response rate according to the BICLA definition, requiring BILAG improvement, no worsening in BILAG, SLEDAI-2K score and PhGA, with no disallowed changes in concomitant medications. Patients who discontinued were classified as non-responders. Results In EMBODY™ 1/EMBODY™ 2, 793/791 patients were randomized, 786 (99.1%)/788 (99.6%) received study medication, and 528 (66.6%)/533 (67.4%) completed the study. There was no statistically significant difference in the primary endpoint between groups: Week 48 BICLA response rates were similar in Epratuzumab and placebo groups (range 33.5–39.8%). No new safety signals were identified. Conclusions Treatment with Epratuzumab+ST did not result in improvements in response rates over placebo+ST. This article is protected by copyright. All rights reserved.

  • long term safety and efficacy of Epratuzumab in the treatment of moderate to severe systemic lupus erythematosus results from an open label extension study
    Arthritis Care and Research, 2016
    Co-Authors: Daniel J. Wallace, Vibeke Strand, Kathryn Hobbs, Michelle Petri, Megan E B Clowse, Marilyn C Pike, Piotr Leszczynski, J T Merrill, C M Neuwelt, Slawomir Jeka
    Abstract:

    Objective The primary objective was to assess the long-term safety of repeated courses of Epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL). Methods Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg Epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed. Results A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued Epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to Epratuzumab. Conclusion Open-label Epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.

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  • a phase 2 trial of extended induction Epratuzumab and rituximab for previously untreated follicular lymphoma calgb 50701
    Cancer, 2013
    Co-Authors: Barbara Grant, John P Leonard, Jeffrey L Johnson, Lale Kostakoglu, John C Byrd, Jeffrey A Jones, Sinho Jung, Eric S Martin, Bruce D Cheson
    Abstract:

    BACKGROUND Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and Epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS Fifty-nine untreated patients with FL received Epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients. Cancer 2013;119:3797–3804. © 2013 American Cancer Society.

  • combination biologic therapy as initial treatment for follicular lymphoma initial results from calgb 50701 a phase ii trial of extended induction Epratuzumab anti cd22 and rituximab anti cd20
    Blood, 2010
    Co-Authors: Barbara Grant, John P Leonard, Jeffrey L Johnson, Lale Kostakoglu, John C Byrd, Jeffrey A Jones, Sinho Jung, Bruce D Cheson
    Abstract:

    Abstract 427 Rituximab is effective as single agent therapy in the treatment of follicular lymphoma (FL), and when combined with chemotherapy has extended remissions and survival. Epratuzumab (Immunomedics), a humanized anti-CD22 monoclonal antibody, also has single agent activity in FL, and in combination with rituximab led to durable complete responses in the treatment of patients (pts) with relapsed and refractory indolent NHL. To evaluate the hypothesis that combining a second biological agent with rituximab might improve efficacy with good tolerability, the CALGB treated 60 previously untreated pts with Epratuzumab and rituximab in a multicenter phase II trial and we report here the preliminary response and toxicity findings. Rituximab was administered at 375 mg/m2 iv weekly for four weeks, then every 8 weeks for four additional doses for a total of 8 doses over 9 months. Epratuzumab, was given at 360 mg/m2 two days before the first rituximab dose to assess toxicity. From week 2 on, Epratuzumab was given before the rituximab on the same day for a total of 8 doses over 9 months. Fifty-seven evaluable pts were enrolled between May 2008 and September 2009. FLIPI scores at study entry were 13 (22%) low; 28 (47.5%) intermediate; and 18 (30.5%) high. Fifty-three pts completed all therapy through month 9. One pt was taken off therapy due to progression after month 5. One pt died during induction from line sepsis. Two pts were taken off study due to adverse events, 1 during induction (grade 4 thrombosis and MI), 1 following month 5 (dyspnea, hypoxia and pulmonary NOS). All other toxicities were grade 3 or lower, including fatigue (grade 3 3%, grade 2 17%), nodal pain (grade 3 5%, grade 2 8%), and cytokine release and pruritis (grade 2, 5% each). To date, there have been 19 CRs (33.3%), 29 PRs (50.9%)(ORR 84.2%); 9 (15.8%) had stable disease. All 19 CR patients completed all treatment. The mean time to CR was 9 months. Two patients progressed after a period of stable disease, and 25 of the 29 patients who achieved PR remain in response. All 19 CRs also remain in remission at this point with a median follow-up of 0.82 years (range 0.52 to 2.0). FLIPI score was not predictive of response. The CR rate in low risk pts was 31%, 44% in intermediate risk and 18% in high risk pts. There was a trend toward higher CR rate among patients with FcgR2A His (n=10, CR 60%) and to a lower CR rate among those with FcgR2A Arg (n=14, CR 14.3%). Correlations with PET scan at week 3, with tissue biomarkers and to statin use are being analyzed. Rituximab and Epratuzumab is an effective and very well tolerated regimen with an ORR of 84% in previously untreated patients with follicular lymphoma. Disclosures: Off Label Use: Use of Epratuzumab, a humanized antiCD22 monoclonal antibody in treatment of follicular lymphoma. Leonard: BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Jones: Glaxo Smith-Kline: Consultancy; Abbott: Research Funding. Cheson: Genentech: Consultancy.

  • durable complete responses from therapy with combined Epratuzumab and rituximab final results from an international multicenter phase 2 study in recurrent indolent non hodgkin lymphoma
    Cancer, 2008
    Co-Authors: John P Leonard, Morton Coleman, Stephen J Schuster, William A Wegener, Nick Teoh, Christos Emmanouilides, Felix Couture, David M Goldenberg
    Abstract:

    BACKGROUND. In this international, multicenter trial, the authors evaluated rituximab (anti-CD20) plus Epratuzumab (anti-CD22) in patients with postchemotherapy relapsed/refractory, indolent non-Hodgkin lymphoma (NHL), including long-term efficacy. METHODS. Forty-nine patients with follicular NHL (FL) (N = 41) or small lymphocytic lymphoma (SLL) (N = 7) received intravenous Epratuzumab 360 mg/m2 and then intravenous rituximab 375 mg/m2 weekly ×4. The regimen was tolerated well. RESULTS. Twenty-two of 41 patients with FL (54%) had an objective response (OR), including 10 (24%) complete responses (CR) (CR/unconfirmed CR [CRu]), whereas 4 of 7 patients with SLL (57%) had ORs, including 3 (43%) with CR/CRu. Rituximab-naive patients (N = 34) had an OR rate of 50% (26% CR/CRu rate), whereas patients who previously responded to rituximab (N = 14) had an OR rate of 64% (29% CR/CRu rate). An OR rate of 85% was observed in patients with FL who had Follicular Lymphoma International Prognostic Index (FLIPI) risk scores of 0 or 1 (N = 13), whereas 28 patients with intermediate or high-risk FLIPI scores (≥2) had an OR rate of 39% (18% CR/CRu rate). In patients with FL, the median response duration was 13.4 months, and that duration increased to 29.1 months for 10 patients who had a CR/CRu, including 4 patients who had durable responses with remissions that continued for >4 years. In patients with SLL, the median response duration was 20 months, including 1 patient who had a response that continued for >3 years. CONCLUSIONS. The combination of Epratuzumab and rituximab induced durable responses in patients with recurrent, indolent NHL. Cancer 2008. © 2008 American Cancer Society.

  • durable complete responses following therapy with Epratuzumab plus rituximab final efficacy results of a multicenter study in recurrent indolent non hodgkin s lymphoma nhl
    Blood, 2007
    Co-Authors: John P Leonard, Stephen J Schuster, William A Wegener, Nick Teoh, Christos Emmanouilides, Felix Couture, David M Goldenberg
    Abstract:

    BACKGROUND: Epratuzumab, an anti-CD22 humanized monoclonal antibody, has shown clinical activity as a single-agent (Leonard et al, J Clin Oncol. 2003; 21:3051–3059) and in combination with rituximab in relapsed/refractory B-cell NHL (Leonard et al, J Clin Oncol. 2005; 23:5044–5051). To evaluate this combination regimen in a larger cohort of patients and to evaluate long-term efficacy, we conducted an international multicenter, open-label, single-arm study in patients with recurrent indolent NHL. METHODS: Forty-nine patients (23F/26M, median age: 61, elevated LDH: 25%, bone marrow involvement: 49%) with chemotherapy-relapsed or refractory follicular NHL (n=41) or small lymphocytic lymphoma (n=7) (as well as one enrolled patient with histological evidence of follicular and diffuse large B-cell lymphoma) were evaluated. Thirty-five (71%) were rituximab-naive, with the remainder having previously received and responded to then relapsed from rituximab (single agent or with chemotherapy). Patients received 360 mg/m2 IV of Epratuzumab, followed by 375 mg/m2 IV of rituximab, weekly for 4 consecutive weeks. RESULTS: As preliminarily reported (Emmanouilides et al, Blood 2003; 102/11:69a), the combination therapy was well tolerated, without notable additive toxicity over that expected with single-agent rituximab. Twenty-two of the 41 (54%, 95% CI: 37% – 69%) follicular NHL (FL) patients achieved an objective response (OR) using IWG response criteria, including 10 (24%) patients with complete responses (CR), half of whom remained in remission at the last evaluation with a median duration of follow-up of 44.3 months (range: 18.2 – 52.4 months). The median duration of response (DR) was 13.4 months (95% CI: 8.4 – 28.2 months) and the median progression-free survival (PFS) was 10.2 months (95% CI: 6.3 – 13.6 months), with a Kaplan-Meier estimated median DR of 33.4 months (range: 11.2 – 47.9 months) and an estimated median PFS of 35.1 months (range: 12.9 – 52.4 months) for the 10 patients who achieved CR. Importantly, 4/7 SLL patients (57%) experienced OR, including 2 CR, 1 CRu and 1 PR. Furthermore, while the rituximab-naive FL and SLL patients (n=34) showed an OR of 50% (26% CR/CRu, 24% PR), those patients who had responded to prior rituximab (n=14) had an OR of 64% (29% CR, 36% PR). CONCLUSIONS: Overall, this study confirms that the combination of Epratuzumab and rituximab, in addition to being well tolerated, demonstrates promising anti-lymphoma activity for indolent NHL, and can result in durable complete remissions in a subset of patients. Further evaluation of this combination regimen as initial therapy for indolent NHL is planned (CALGB 50701), and in diffuse large B cell lymphoma (CHOP + Epratuzumab + rituximab) is ongoing (NCCTG N0489).

  • preclinical and clinical evaluation of Epratuzumab anti cd22 igg in b cell malignancies
    Oncogene, 2007
    Co-Authors: John P Leonard, David M Goldenberg
    Abstract:

    The vast majority of non-Hodgkin's lymphomas are of B-cell phenotype. Development of unlabeled or radiolabeled therapeutic monoclonal antibodies against the cell surface antigen, CD20, has revolutionized the treatment of these malignancies. It is clear that antibodies targeting other B-cell-specific molecules, such as CD22, also offer potential therapeutic benefit. Epratuzumab is a humanized anti-CD22 monoclonal, which has undergone preclinical and phase I/II clinical evaluation in patients with indolent or aggressive lymphoma. Data suggest that this agent is well tolerated, and can induce tumor regressions. Trials are currently evaluating its safety and activity in combination with rituximab (chimeric anti-CD20) and standard chemotherapy are ongoing. Initial results suggest that these regimens have acceptable toxicity, and that Epratuzumab warrants further evaluation as an adjunct to standard lymphoma treatment regimens.