scholarly journals Application of monoclonal anti-CD20 antibody rituximab in the treatment of non-Hodgkin's lymphoma

2008 ◽  
Vol 65 (3) ◽  
pp. 229-233
Author(s):  
Biljana Mihaljevic ◽  
Snezana Jankovic ◽  
Ljubomir Jakovic ◽  
Maja Jovanovic-Perunicic ◽  
Bosko Andjelic ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

<zakljucak> Nehockinski limfomi danas predstavljaju kamen temeljac savremenoj onkohematologiji, s obzirom na mogucnost visokog procenta njihovog izlecenja. Najcesca podgrupa limfoma su DBKL koji su kod oko 30% bolesnika izlecivi primenom konvencionalne terapije, dok su FL neizlecivi ukoliko se lece samo konvencionalnom terapijom. Istina je da se kod bolesnika sa FL terapijski odgovor postize brzo, ali recidivi se gotovo po pravilu desavaju i bolesnike je u svakom sledecem recidivu sve teze leciti. Sredinom devedestih godina napravljeno je prvo monoklonsko antitelo u lecenju malignih bolesti, i to najpre za recidive ili refraktarne FL. Ovo anti CD20 monoklonsko antitelo, rituksimab, predstavlja krucijalan napredak u lecenju limfoma, jer je primenom kombinoivane imunohemioterapije izlecenje DBKL poraslo na oko 60%, a poslednje studije ukazuju na mogucnost dugotrajnih remisija i PFS za FL, sto moze biti ekvivalent izlecenju i ove podgrupe limfoma. U toku su brojne studije kojima se vrse uporedne analize za primenu ritoksimaba i kod drugih podtipova limfoma kao sto je limfom marginalne zone, mantle celijski limfom, Hockinova bolest, a uvode se indikacije i za pojedine sistemske bolesti vezivnog tkiva, kao sto je reumatoidni artritis.

Interim Results of a Phase I/II Study of Ocrelizumab, a New Humanised Anti-CD20 Antibody in Patients with Relapsed/Refractory Follicular Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 645-645 ◽  
Author(s):  
Franck Morschhauser ◽  
Paula Marlton ◽  
Umberto Vitolo ◽  
Ola Linden ◽  
John Seymour ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Open Label ◽  
Dose Escalation Study ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd20 Antibody ◽  
Grade 3 ◽  
Anti Cd20

Abstract Background: Ocrelizumab is a new humanised anti-CD20 antibody with the potential for enhanced efficacy in non-Hodgkin’s lymphoma (NHL) compared with rituximab due to increased binding affinity for the low-affinity variants of the FcγRIIIa receptor. An open-label, multicentre, dose-escalation study was conducted to evaluate the safety, efficacy, pharmacokinetics and pharmacogenetics of ocrelizumab in patients (pts) with relapsed/refractory follicular NHL following prior rituximab-containing therapy. Methods: A total of 47 pts with a response (complete response [CR], unconfirmed CR [CRu], partial response [PR]) or stable disease (SD) of ≥6 months’ duration following prior rituximab-containing treatment were enrolled into 3 sequential dose cohorts. Pts received infusions of ocrelizumab q3w at 200 mg/m2 (cohort A), 375 mg/m2 (cohort B) and 750 mg/m2 (cohort C) for up to 8 doses. Response was assessed after 4 doses and after the end of treatment. Results: Fifteen pts were enrolled in cohort A, 16 in cohort B and 16 in cohort C; 60% were male; mean age was 57 years; 78% had stage III/IV disease. At study entry 30%, 50% and 67% had intermediate or high FLIPI score in cohorts A, B and C, respectively. Median number of prior therapies was 2 (range 1–7); time to progression after last rituximab-containing therapy of <12 months: 47% (cohort A), 31% (cohort B) and 62% (cohort C) of pts. The majority of pts reported ≥1 adverse event (AE) [80–100%, cohorts A-C]; most of these were grade 1/2, with only 6 pts experiencing a grade 3 AE and no grade 4 AEs observed. The most common AEs were infusion-related reactions (IRR; 73%, 75% and 69% in cohorts A, B and C, respectively); only one was grade 3. Two pts discontinued treatment due to toxicity (dyspnoea, IRR). A total of 17 pts responded to ocrelizumab for a response rate (RR) of 36% (13% CR/CRu) across all cohorts. RR by cohort was 27% (13% CR/CRu) for A, 50% (25% CR/CRu) for B and 31% (no CR/CRu) for C. In pts relapsing after prior response (CR/PR) to rituximab-containing therapy (n=40), RRs were 23% (15% CR/CRu), 62% (31% CR/CRu) and 33% (no CR/CRu) in cohorts A, B and C, respectively. Of 6 pts with SD after prior rituximab-containing therapy, 1 pt had a PR, 4 pts had SD and 1 pt progressed. Conclusion: Ocrelizumab is well tolerated at doses up to 750 mg/m2 given q3w; AEs consist mainly of grade 1/2 IRRs. Severe IRRs (grade 3/4) following ocrelizumab occur less frequently than with rituximab. In this heavily and rituximab-pretreated pt population, the RR of 36% is encouraging.

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.

Biodistribution and kinetics of 131I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma

2002 ◽  
Vol 29 (10) ◽  
pp. 1276-1282 ◽  
Author(s):  
Klemens Scheidhauer ◽  
Ingo Wolf ◽  
Hans-Joachim Baumgartl ◽  
Christoph von Schilling ◽  
Burkhard Schmidt ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20 ◽  
Kinetics Of
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