scholarly journals Increase in Antibody Titers Following Sars-Cov-2 Vaccination Remains Limited for More Than 3 Years after Final Dose of Anti-CD20 Antibody

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 534-534
Author(s):  
Yohei Funakoshi ◽  
Kimikazu Yakushijin ◽  
Goh Ohji ◽  
Hironori Sakai ◽  
Wataru Hojo ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Final Dose ◽  
Chugai Pharmaceutical ◽  
Antibody Titers ◽  
Ifn Γ ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. Patients with hematological disorders are known to be at high risk of morbidity and mortality from COVID-19, and vaccines against SARS-CoV-2 have been rapidly developed. Although mRNA vaccines against SARS-CoV-2 are reported to be effective, efficacy in patients with hematological malignancies who have received anti-CD20 antibody treatment remains unclear. Here, we prospectively evaluated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. We first evaluated antibody titers in 12 healthy volunteers (median age 75.5 years, range 57-82) and three lymphoma patients undergoing R-CHOP therapy (73, 81, and 81 years old) who had received 2 vaccine doses of BNT162b2 at pre-vaccination, 21 days after the first dose and 14 days after the second dose of vaccination. IgG antibody titers for S1 protein were measured in serum samples by ELISA. In healthy control subjects, titers were clearly increased. In contrast, no patient treated with R-CHOP developed antibodies even after the second vaccination (Figure A). To determine the SARS-CoV-2-specific T-cell reactivity in these three patients, we evaluated interferon (IFN)-γ response to the SARS-CoV-2 spike peptide before and after the second vaccination dose, and detected IFN-γ responses after vaccination in all three patients (Figure B). Next, to investigate the duration of the effect of anti-CD20 antibody on antibody production to BNT162b2, we enrolled 36 patients (median age 74 years, range 50-87) who had received the final dose of anti-CD20 antibody 48-1320 (median 571) days before vaccination. S1 antibody titers were measured 14 days after the second dose of vaccination. Diagnoses included diffuse large B-cell lymphoma (n = 21), follicular lymphoma (n = 9), lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (n = 3), and mantle cell lymphoma (n = 3). Thirty-four patients had received rituximab-based and 2 had received obinutuzumab-based therapy, with a median of 6 (range 3-20) courses. No patient had received any chemotherapy after the last anti-CD20 antibody dose. No patient vaccinated within close to one year or sooner after the last anti-CD20 antibody administration showed an increase in titers. Furthermore, titers in most patients were lower than in healthy volunteers even among those vaccinated more than three years after the last administration (Figure C). Finally, we investigated surrogate markers of antibody production ability. We found no relationship between the percent of B-cells (CD19-positive cells) and S1 antibody titers (Figure D), whereas all patients (n = 9) with total IgG level below lower normal limit (< 870 mg/dl) had low S1 antibody titers (< 0.16), below the lowest optical density (O.D.) value in healthy donors (Figure E). These findings indicate that the antibody-mediated response to vaccination in patients following treatment with anti-CD20 antibody was considerably impaired for an extended time. Alternative protection strategies for these patients are therefore warranted. Although T-cell responses were detected, we recommend that these patients continue to wear a face mask and wash their hands to prevent COVID-19 even after vaccination. Figure 1 Figure 1. Disclosures Yakushijin: Chugai pharmaceutical Co. Ltd.: Research Funding; Jazz pharmaceuticals: Research Funding; Nippon Shinyaku: Honoraria. Kiyota: Bristol-Myers Squibb: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Astra-Zeneca: Honoraria, Research Funding; Roche Phamaceuticals: Research Funding; Merck Biopharma: Honoraria; Merck Sharp & Dohme: Honoraria; Eisai: Honoraria; Bayer: Honoraria. Matsuoka: Takeda Pharmaceutical Company: Research Funding; Sysmex: Research Funding. Minami: Behring: Research Funding; CSL: Research Funding; Yakult Honsha: Research Funding; Nippon Shinyaku: Research Funding; Astellas Pharma: Research Funding; Asahi-Kasei Pharma: Research Funding; Eli Lilly: Honoraria, Research Funding; Taiho Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Merck Serono: Honoraria, Research Funding; Kyowa-Kirin: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; DaiichiSankyo: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer Yakuhin: Honoraria, Research Funding; Nippon Kayaku: Research Funding; Celgene: Honoraria; Ohtsuka Pharmaceutical: Honoraria; Shire Japan: Honoraria; Genomic Health: Honoraria; Abbvie: Honoraria.

scholarly journals Imaging the mechanisms of anti-CD20 therapy in vivo uncovers spatiotemporal bottlenecks in antibody-dependent phagocytosis

2021 ◽  
Vol 7 (8) ◽  
pp. eabd6167
Author(s):  
Capucine L. Grandjean ◽  
Zacarias Garcia ◽  
Fabrice Lemaître ◽  
Béatrice Bréart ◽  
Philippe Bousso
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Critical Path ◽  
B Cell Lymphoma ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Fluorescent Reporter ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Partial Depletion

Anti-CD20 antibody (mAb) represents an effective strategy for the treatment of B cell malignancies, possibly involving complement activity, antibody-dependent cellular cytotoxicity and phagocytosis (ADP). While ADP by Kupffer cells deplete circulating tumors, mechanisms targeting non-circulating tumors remain unclear. Using intravital imaging in a model of B cell lymphoma, we establish here the dominance and limitations of ADP in the bone marrow (BM). We found that tumor cells were stably residing in the BM with little evidence for recirculation. To elucidate the mechanism of depletion, we designed a dual fluorescent reporter to visualize phagocytosis and apoptosis. ADP by BM-associated macrophages was the primary mode of tumor elimination but was no longer active after one hour, resulting in partial depletion. Moreover, macrophages were present at low density in tumor-rich regions, targeting only neighboring tumors. Overcoming spatiotemporal bottlenecks in tumor-targeting Ab therapy thus represents a critical path towards the design of optimized therapies.

Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma

1997 ◽  
Vol 25 (2) ◽  
pp. 705-708 ◽  
Author(s):  
D. R. Anderson ◽  
A. Grillo-López ◽  
C. Varns ◽  
K. S. Chambers ◽  
N. Hanna
Keyword(s):  
Cancer Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Anti Cancer ◽  
Cd20 Antibody ◽  
Anti Cd20

Discrepancy of CD20 Protein Expression In IHC and FCM Analyses In Primary B-Cell Lymphoma: Relationship Between FCM-Negative Phenotype and Rituximab Binding with Lymphoma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5087-5087 ◽  
Author(s):  
Takashi Tokunaga ◽  
Akihiro Tomita ◽  
Kazuyuki Shimada ◽  
Junji Hiraga ◽  
Takumi Sugimoto ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Lymphoma ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Lymphoma Cells ◽  
Anti Cd20

Abstract Abstract 5087 Background Rituximab is an anti-CD20 chimeric-monoclonal antibody, and its effectiveness for treatment of CD20-positive B-cell lymphomas has been proven over the past 10 years. Although rituximab is now a key molecular targeting drug for CD20-positive lymphomas, some patients with rituximab resistance have emerged. We previously reported that the CD20-protein-negative phenotypic change after using rituximab is one of the critical mechanisms in rituximab resistance (Hiraga J, Tomita A, et al., Blood, 2009., Sugimoto T, Tomita A, et al., Biochem Biophys Res Commun, 2009.). Recently, we have recognized that some newly-diagnosed B-cell lymphomas show CD20-protein-positive in immunohistochemistry (IHC) but -negative in flow cytometry (FCM) analyses. For these patients, so far, neither the molecular mechanisms of CD20 IHC(+)/FCM(−) phenotype, nor the relationship between this phenotype and rituximab resistance are clear. Thus, the clinical significance of introducing rituximab therapy for these patients must be elucidated. Aims Analyses of the molecular backgrounds of CD20 IHC(+)/FCM(−) phenotype in primary B-lymphoma cells, and confirmation of the effectiveness of rituximab therapy for the patients who show CD20 IHC(+)/FCM(−) phenotype. Results Primary B-cell lymphoma (diffuse large B-cell (DLBCL), follicular, MALT, mantle cell, and Burkitt) tissues and cells were analyzed by IHC and FCM. Four newly-diagnosed B-cell lymphoma patients showed IHC CD79(+)/CD20(+) and FCM CD19(+)/CD20(−) phenotype using anti-CD20 antibodies L26 for IHC and B1 for FCM, and all were diagnosed as DLBCL. Chromosomal analysis showed complex karyotypes in 3 out of 3 patients analyzed, and no shared abnormalities were confirmed. Primary lymphoma cells from 3 patients were available for further molecular analyses, and the genomic DNA, the total RNA, and the protein from whole cell lysate were obtained from these lymphoma cells. DNA sequencing analysis indicated no significant genetic mutations on the coding sequences (CDS) of MS4A1 (CD20) gene. Semi-quantitative and quantitative RT-PCR indicated that CD20 mRNA expression was almost normal in 2 patients and ≂~f10 times lower in 1 patient compared to the positive control B-lymphoma/leukemia cells. Almost the same expression tendency with RT-PCR was confirmed in immunoblot analysis using whole cell lysate and the two different anti-CD20 antibodies. The molecular weight of the CD20 protein in immunoblotting corresponded to the wild type in these patients. Rituximab binding assay in vitro was performed using primary lymphoma cells from a patient and the fluorescent-labeled rituximab (Alexa488-rituximab). Interestingly, rituximab binding on the surface of the CD19 positive lymphoma cells was confirmed in vitro. Rituximab containing combination chemotherapy was performed, resulting in complete response in all 4 cases after completing 4 to 8 courses. Conclusions and Discussion CD20 IHC(+)/FCM(−) phenotype was confirmed in newly-diagnosed DLBCL patients. Significant abnormalities in CD20 protein and mRNA expression in immunoblotting and RT-PCR were not confirmed, and genetic mutations on CDS of MS4A1 gene, resulting in the conformation change of CD20 protein, were not detected. The possibility of abnormal post-translational modification or aberrant localization of CD20 protein, leading to interference with antibody binding, can not be excluded. Rituximab binding with CD19-positive primary lymphoma cells was confirmed in a patient, suggesting that CD20 IHC(+)/FCM(-) phenotype does not directly indicate the ineffectiveness of rituximab for these cells. Further investigations, performing in vitro CDC and ADCC assay using primary lymphoma cells, are still warranted to show rituximab effectiveness and sensitivity to those cells. Disclosures: Kinoshita: Zenyaku Kogyo Co.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Naoe:Zenyaku Kogyo Co.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding.

LFB-R603, a Third-Generation Monoclonal Anti-CD20 Antibody Displays An Additive Antitumor Activity with Antileukemic Chemotherapeutic Agents in Mouse Xenograft Models

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1660-1660 ◽  
Author(s):  
Isabel Tourais Esteves ◽  
Charles Dumontet ◽  
Stéphanie Herveau ◽  
Lina Reslan ◽  
Frédérique Brune ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Mantle Cell Lymphoma ◽  
Subcutaneous Injection ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Chemotherapeutic Agents ◽  
Mantle Cell ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 1660 LFB-R603, a next generation anti-CD20 antibody currently in clinical development, is characterized by a specific glycosylation pattern containing a high percentage of non fucosylated antibodies molecules at the Fc site. This pattern of glycosylation increases the affinity of antibodies for human FcγRIIIa, resulting in an increased antibody dependent cell-mediated cytotoxicity (ADCC) by human FcγRIIIa-expressing effector cells. This antibody is currently in a phase I clinical trial in B-CLL patients and its use is planned to be expanded to other non-hodgkin's lymphomas (NHL) such as follicular and mantle cell lymphoma, as a single agent and in combination with chemotherapeutic agents. The antitumor efficacy of LFB-R603 was studied in comparison with rituximab in combination with conventional chemotherapeutic agents in two models of NHL developed in immuno-deficient mice. The RL cell line, derived from a patient with follicular lymphoma (FL), was xenografted in mice by subcutaneous injection. Tumor-bearing mice were treated intravenously during 4 weeks with the anti-CD20 antibodies used alone or in combination with suboptimal doses of cyclophosphamide 50 mg/kg or bendamustine 30 mg/kg. LFB-R603 and rituximab displayed a dose-related antitumor activity. The tumor growth inhibition (TGI) was at day 30, 64% at 10 mg/kg, 84% at 30 mg/kg and 100% at 100 mg/kg for LFB-R603 compared with the untreated-group. For rituximab, the TGI was 84% at 30 mg/kg and 99% at 100 mg/kg. More interestingly, LFB-R603 at 100 mg/kg dose showed a significantly superior antitumor activity as a delay of 21 days in tumor growth was observed compared to rituximab (p=0.00001). The combination of LFB-R603 or rituximab at 60 mg/kg with cyclophosphamide enhanced the effect observed with the antileukemic agent only and the additive effect was similar for the two antibodies as a delay of 13 days in tumor growth was observed for both combination-treated groups compared with the cyclophosphamide-treated group (p=0.00001). However, LFB-R603 displayed a significant higher antitumor activity against RL xenografts than rituximab when combined with bendamustine as a tumor growth delay of 7 days was observed between the two treated-groups (p=0.00001). The NCEB cell line, derived from a patient with mantle cell lymphoma (MCL), was xenografted in mice by subcutaneous injection. In this model, LFB-R603 and rituximab injected once weekly up to 3 weeks displayed a dose-related TGI activity. A higher activity of LFB-R603 compared to rituximab was observed at all tested doses (3, 10, 30 and 60 mg/kg). TGI values at day 51 were 91% for LFB-R603 at 3 mg/kg versus 40% for rituximab, 88% for LFB-R603 at 10 mg/kg versus 57 % for rituximab and 100% for LFB-R603 at 30 and 60 mg/kg versus 66% for rituximab when compared with untreated-group. In conclusion, LFB-R603 displayed a greater antitumor activity as compared to rituximab in two different non-clinical in vivo models of NHL, namely follicular and mantle cell lymphoma. Moreover, additive effects were obtained when LFB-R603 was combined with chemotherapeutic agents such as cyclophosphamide and bendamustine in the FL model. Disclosures: Tourais Esteves: LFB Biotechnologies: Employment. Dumontet:LFB Biotechnologies: Research Funding. Herveau:LFB Biotechnologies: Research Funding. Reslan:LFB Biotechnologies: Research Funding. Brune:LFB Biotechnologies: Employment. Van Overtvelt:LFB Biotechnologies: Employment. Salcedo:LFB Biotechnologies: Employment. Fournès:LFB Biotechnologies: Employment.

Differential Patterns of Gene Expression and CD20 Localisation by the Type II Anti-CD20 Antibody Obinutuzumab (GA101) Compared with the Type I Antibody Rituximab Suggests Binding to Functionally Distinct CD20 Subpopulations on B-Cell Lymphoma Cell Lines,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3721-3721
Author(s):  
Gerhard Niederfellner ◽  
Olaf Mundigl ◽  
Alexander Lifke ◽  
Andreas Franke ◽  
Ute Baer ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mechanisms Of Action ◽  
Type I ◽  
Type Ii ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 3721 The anti-CD20 antibody rituximab has become central to the treatment of B-cell malignancies over the last decade. Recently, it has been shown that anti-CD20 antibodies can be divided into two types based on their mechanisms of action on B cells. Rituximab is a type I antibody that redistributes CD20 into lipid rafts and promotes complement-dependent cytotoxicity (CDC), while the type II, glycoengineered antibody GA101 has lower CDC activity but higher antibody-dependent cellular cytotoxicity and direct cell death activity. In preclinical studies GA101 was superior to rituximab in B-cell killing in vitro, depletion of B cells from whole blood, and inhibition of tumour cell growth in lymphoma xenograft models. GA101 is currently being evaluated in Phase II/III trials, including comparative studies with rituximab. To investigate the differences in direct effects of GA101 and rituximab on B-cell lymphoma signaling, we have analysed the effects of antibody binding on gene expression in different B-cell lines using a GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix). Rituximab and GA101 rapidly induced gene expression changes in SUDHL4 and Z138 cells, including regulation of genes associated with B-cell-receptor activation such as EGR2, BCL2A1, RGS1 and NAB2. The effects on gene expression differed markedly between different cell lines and between the two antibodies. SUDHL4 cells showed pronounced changes in the gene expression pattern to rituximab treatment, while Z138 cells, which represent a different B-cell stage, showed less pronounced changes in gene expression. The reverse was true for GA101, suggesting not only that the signaling mediated by CD20 differs in different cell lines, but also that in a given cell line the two types of antibodies bind CD20 molecules with different signaling capacity. For each cell line, gene expression induced by other type I antibodies (LT20, 2H7, MEM97) was more like rituximab and that induced by other type II antibodies (H299/B1, BH20) was more like GA101 in terms of the number of genes regulated and the magnitude of changes in expression. Unbiased hierarchical clustering analysis of gene expression in SUDHL4 could discriminate type I from type II antibodies, confirming that the two classes of antibody recognised CD20 complexes with inherently different signalling capacities. By confocal and time-lapse microscopy using different fluorophores, rituximab and GA101 localised to different compartments on the membrane of lymphoma cells. GA101/CD20 complexes were relatively static and predominantly associated with sites of cell–cell contact, while rituximab/CD20 complexes were highly dynamic and predominantly outside areas of contact. These findings suggest that type II antibodies such as GA101 bind distinct subpopulations of CD20 compared with type I antibodies such as rituximab, accounting for the differences in mechanisms of action and anti-tumour activity between these antibodies. Disclosures: Niederfellner: Roche: Employment. Mundigl:Roche: Employment. Lifke:Roche: Employment. Franke:Roche: Employment. Baer:Roche: Employment. Burtscher:Roche: Employment. Maisel:Roche: Employment. Belousov:Roche: Employment. Weidner:Roche: Employment. Umana:Roche: Employment, Patents & Royalties. Klein:Roche: Employment, Equity Ownership, Patents & Royalties.

Results of A Phase I Study of Milatuzumab, a Humanized Anti-CD74 Antibody, and Veltuzumab, a Humanized Anti-CD20 Antibody, In Patients with Relapsed and Refractory B-Cell Non-Hodgkin's Lymphoma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3707-3707
Author(s):  
Beth Christian ◽  
Lapo Alinari ◽  
Jeffrey A. Jones ◽  
Don M Benson ◽  
Joseph M. Flynn ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prior Therapy ◽  
Infusion Reactions ◽  
Cd20 Antibody ◽  
Grade 3 ◽  
Anti Cd20 ◽  
Dose Levels

Abstract Abstract 3707 Background: Preclinical studies conducted at our institution (Alinari et al. Blood. 2011;117:4530–41) demonstrated superior efficacy of milatuzumab (Immunomedics, Inc.), a humanized anti-CD74 antibody, in combination with rituximab in vitro and in an in vivo preclinical model of mantle cell lymphoma (MCL), compared to either agent alone. Veltuzumab (Immunomedics, Inc.), a humanized anti-CD20 antibody, has been reported to have several advantages over rituximab including slower off-rates, shorter infusion times, higher potency, and improved therapeutic responses in animal models. As a result of the anti-tumor activity observed in vitro with combined veltuzumab and milatuzumab, we initiated a phase I/II trial in pts with relapsed or refractory B-cell NHL after at least 1 prior therapy to determine the safety, tolerability, and overall response rate with this combination. Methods: Pts received veltuzumab 200 at mg/m2 weekly combined with escalating doses of milatuzumab at 8, 16, and 20 mg/kg twice per wk of wks 1–4, 12, 20, 28, and 36. All pts received premedication with acetaminophen, diphenhydramine, hydrocortisone 50 mg, and famotidine prior to veltuzumab and milatuzumb doses. Dose limiting toxicity (DLT) was defined during weeks 1–4. Although not defined as DLT, 3 of the first 6 pts enrolled at dose levels 1–2, had significant grade 3 infusion reactions with milatuzumab. The study was amended to separate veltuzumab and milatuzumab dosing days and add 20 mg dexamethasone immediately prior to and 10 mg post-milatuzumab. Enrollment resumed with 3 additional pts at dose levels 1 and 2 in order to determine if tolerability was improved. Results: The phase I study has completed enrollment with 18 pts (follicular NHL grade 1–2 n=5; grade 3 n=5; transformed follicular n=1; diffuse large B-cell lymphoma (DLBCL) n=4; marginal zone lymphoma (MZL) n=1; MCL n=1; and lymphoplasmacytic lymphoma n=1) that have completed at least 4 weeks of combination therapy. Median age was 65 years (range 44–81), and pts received a median of 3 prior therapies (range 1 – 9), including 3 pts who had undergone prior autologous stem cell transplant. Ten of 18 (56%) pts were refractory to rituximab defined as having less than a partial response to the last rituximab-containing regimen. No DLTs were observed, and no pts experienced grade 3 infusion reactions after the protocol was modified. Other grade 3–4 toxicities at least possibly related to protocol therapy consisted of lymphopenia (n=8, 44%), fatigue (n=2, 11%), neutropenia (n=1, 6%), hyperglycemia (n=1, 6%), and anemia (n=1, 6%). Grade 1–2 infections (n=5, 27%) included thrush, sinusitis, and pneumonia with no pts requiring dose delays or hospitalization. Other frequently observed grade 1–2 toxicities were transient hyperglycemia (n=12, 66%), thrombocytopenia (n=11, 61%), reversible infusion reactions (n=9, 50%), fatigue (n=8, 44%), leukopenia (n=8, 44%), and anemia (n=7, 39%). Human anti-veltuzumab and anti-milatuzumab antibodies, collected pretreatment and day 1 of weeks 4, 12, and 36, have not been detected in any pt. Pharmacokinetic data available from 16 pts through week 10 indicated mean plasma veltuzumab and milatuzumab concentrations immediately post-infusion were 108 ± 7 and 296 ± 22 μg/mL, and mean trough levels were 47 ± 7 and 3 ± 0.3 μg/mL, respectively. All 18 pts were assessable for response at wk 5 with 5 pts currently remaining on active therapy and 4 pts completing treatment through wk 36. To date, complete response was observed in 1 pt with grade 1–2 follicular NHL (3 prior therapies) who was rituximab-refractory and ultimately underwent allogeneic transplant. Partial responses were observed in 3 pts; 2 with grade 3 follicular NHL refractory to rituximab (3 prior therapies including autologous transplant and 5 prior therapies, respectively) and 1 with MZL (1 prior therapy). All responding pts achieved response following induction therapy. Stable disease was observed in 10 pts; of these pts, 6 pts had SD of a median duration of 6 months (range 2.5–10 months) and 4 remain on active therapy. Conclusions: Combination therapy with veltuzumab and milatuzumab was well-tolerated in a population of heavily pre-treated pts with relapsed or refractory NHL. 14/18 pts had evidence of antitumor activity with 22% having an objective overall response, including rituximab-refractory pts. Disclosures: Christian: Immunomedics, Inc.: Research Funding. Off Label Use: Veltuzumab and milatuzumab in non-Hodgkin's lymphoma is off-label drug use. Wegener:Immunomedics, Inc.: Employment, Management and Stock / Stock-options. Goldenberg:Immunomedics, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Sign in / Sign up

Export Citation Format

Share Document