scholarly journals Treatment of B-cell non-Hodgkin's lymphoma with anti-CD20 monoclonal antibodies.

2002 ◽  
Vol 17 (1) ◽  
pp. 35-41
Author(s):  
Kensei Tobinai
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines

2005 ◽  
Vol 23 (26) ◽  
pp. 6421-6428 ◽  
Author(s):  
David G. Maloney
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Patient Specific ◽  
Chimeric Antibody ◽  
Target Antigen ◽  
Host Immune System ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.

Novel and Engineered Anti–B-Cell Monoclonal Antibodies for Non-Hodgkin’s Lymphoma

2008 ◽  
Vol 45 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Peter Martin ◽  
Richard R. Furman ◽  
Jia Ruan ◽  
Rebecca Elstrom ◽  
Jacqueline Barrientos ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Subcutaneous Injections of Low Doses of Humanized Anti-CD20 Veltuzumab for Treatment of Indolent B-Cell Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3757-3757 ◽  
Author(s):  
O. George Negrea ◽  
Steven L Allen ◽  
Kanti R. Rai ◽  
Rebecca Elstrom ◽  
Rashid Abassi ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Hodgkin's Lymphoma ◽  
B Cell Malignancies ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20 ◽  
Dose Levels

Abstract Abstract 3757 Poster Board III-693 Background Low IV doses of veltuzumab, a 2nd generation humanized anti-CD20 monoclonal antibody with structure-function differences from chimeric rituximab, have shown clinical activity in non-Hodgkin's lymphoma (Morschhauser et al., J Clin Oncol, 2009; 27:3346-53). By avoiding lengthy IV administration and the need for dedicated infusion suites, subcutaneous (SC) injections of low-dose veluzumab may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies, and this may be particularly useful in the setting of indolent disease. Methods A multicenter, phase I/II study was undertaken to evaluate the safety, tolerability, and preliminary efficacy of SC veltuzumab in previously untreated or relapsed CD20+ indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). All patients (pts) received 4 SC injections of veltuzumab 2 weeks apart at dose levels of 80, 160, or 320 mg. Efficacy was assessed by CT-based IWG (NHL) or hematology-based NCI/IWCLL (CLL) criteria 4 and 12 weeks later, with responding pts continuing follow-up. Other evaluations included AEs, safety laboratories, B-cell blood levels (CD19), serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Twenty-six pts (10M/16F, median age 64), including 15 NHL pts (12 follicular, 3 other indolent NHL; 5 treatment naïve) most with stage III or IV disease (12/15), and 11 CLL pts (4 treatment naïve) most with Rai stage II or III disease, have now received SC veltuzumab at 80 mg (3 NHL, 3 CLL), 160 mg (9 NHL, 3 CLL) or 320 mg (3 NHL, 5 CLL) dose levels. Pre-treatment with antihistamines or steroids was not required. SC veltuzumab was well tolerated with only mild, transient injection-site reactions and tenderness, and no other safety issues. To date, all HAHA response results have been negative. In NHL pts, SC veltuzumab demonstrated good bio-availability, with a slow release pattern over several days, and a mean Cmax of 18.7, 19.5 and 64.0 μg/mL at 80, 160, and 320 mg dose levels, respectively. Depletion of circulating B cells was observed starting after 1st injection. In the 15 NHL pts, the objective response rate (CR+CRu+PR) was 53% (8/15) with a complete response (CR) rate of 20% (3/15) and with 7/8 ORs currently continuing in remission, up to 6 months after treatment. The 11 CLL pts presented with mean white blood cell levels of 55K/μL (maximum 122K/μL) and achieved much lower serum veltuzumab levels, with mean Cmax values of 4.0, 2.5 and 21.0 μg/mL at the 80, 160, and 320 mg dose levels, respectively. There were no ORs, but 5 of 7 (71%) CLL pts with response assessments currently available showed stable disease with >70% decreases in B-cell levels for up to 12 weeks. Conclusions SC administration of veltuzumab is well tolerated, achieves slow but efficient delivery into the blood, and is pharmacologically active when given every 2 weeks for a total of 4 doses. In CLL with high levels of circulating leukemic cells, more frequent and prolonged dosing is likely required. However, in NHL, these low SC doses achieved sustained serum levels with objective response rates comparable to those seen even with higher IV doses. Disclosures: Negrea: Immunomedics: Research Funding. Off Label Use: veltuzumab for investigational treatment of NHL/CLL. Allen:Immunomedics: Research Funding. Rai:Immunomedics: Research Funding. Elstrom:Immunomedics: Research Funding. Abassi:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Teoh:Immunomedics: Employment. Horne:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

Humanized Anti-CD20 Antibody, Veltuzumab, in Refractory/Recurrent Non-Hodgkin's Lymphoma: Phase I/II Results

2009 ◽  
Vol 27 (20) ◽  
pp. 3346-3353 ◽  
Author(s):  
Franck Morschhauser ◽  
John P. Leonard ◽  
Luis Fayad ◽  
Bertrand Coiffier ◽  
Marie-Odile Petillon ◽  
...  
Keyword(s):  
Phase I ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Dose Levels

Purpose This is a multicenter phase I/II dose-finding study in relapsed/refractory B-cell non-Hodgkin's lymphoma (NHL) evaluating veltuzumab, a humanized anti-CD20 antibody with structure-function differences from chimeric rituximab. Patients and Methods Eighty-two patients (median age, 64 years; 79% stage III/IV, one to nine prior treatments) received four once-weekly doses of 80 to 750 mg/m2 of veltuzumab and were assessed for safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity. Results Veltuzumab was well tolerated, with no grade 3 to 4 drug-related adverse events despite short infusion times (typically 2 hours initially, 1 hour subsequently at doses < 375 mg/m2). In follicular lymphoma, 24 (44%) of 55 patients had objective responses (OR), with 15 (27%) complete responses (CRs) or CRs unconfirmed (CRus) by International Working Group criteria, and with some responses occurring despite two to five prior rituximab-containing regimens, less favorable prognosis (elevated lactate dehydrogenase, tumors > 5 cm, and Follicular Lymphoma International Prognostic Index ≥ 2), and at all dose levels. The CRs/CRus were durable (median duration, 19.7 months), with five patients still ongoing (15.9 to 37.6 months duration). In marginal zone lymphoma, five (83%) of six patients had ORs, with two CRs/CRus (33%), and in diffuse large B-cell lymphoma, three (43%) of seven patients achieved partial responses. At all dose levels studied, B cells were depleted after the first infusion, veltuzumab serum half-lives were similar after the fourth infusion, and mean antibody serum levels exceeded values considered important for anti-CD20 therapy (ie, 25 μg/mL). Conclusion Veltuzumab appeared safe and active at all tested doses, encouraging further study, including dose levels less than those typically used with rituximab.

Phase II Study of Rituximab in Combination With CHOP Chemotherapy in Patients With Previously Untreated, Aggressive Non-Hodgkin’s Lymphoma

2001 ◽  
Vol 19 (2) ◽  
pp. 389-397 ◽  
Author(s):  
J. M. Vose ◽  
B. K. Link ◽  
M. L. Grossbard ◽  
M. Czuczman ◽  
A. Grillo-Lopez ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Chop Chemotherapy ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score ≥ 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score ≥ 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score ≥ 2 warrants further investigation with a randomized study.

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