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Basis for initial approval:
Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.
J Clin Oncol. 1998 Aug;16(8):2825-33. PMID: 9704735
From 31 centers, 166 patients were entered. Of this intent-to-treat
group, 48% responded.
With a median follow-up duration of 11.8 months, the projected median
time to progression for responders is 13.0 months.
... the majority of adverse events occurred during the first infusion
and were grade 1 or 2; fever and chills were the most common
events. Only 12% of patients had grade 3 and 3% grade 4
toxicities. A human antichimeric antibody was detected in only one
patient.
CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to
results with single-agent cytotoxic chemotherapy. Toxicity was mild.
Attention needs to be paid to the rate of antibody infusion, with
titration according to toxicity.
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Review Articles on Rituxan
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Basis for approval: Rituximab therapy for indolent non-Hodgkin's lymphoma.
Anticancer Drugs. 2002 Nov;13 Suppl 2:S11-7. Review. PMID: 12710586
In the pivotal study for rituximab, patients with relapsed or
refractory indolent or follicular lymphoma (FL) had an overall
response rate of 50%.
There is evidence that first-line rituximab therapy may be
associated with better response rates; in previously untreated FL
with a low tumor burden, rituximab monotherapy has produced an
overall response rate of 73%.
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Rituxan and Beyond - Medscape
(free login req.)
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Rituximab: ongoing and future clinical development.
Semin Oncol. 2002 Feb;29(1 Suppl 2):105-12.
Review. PMID:
11842397 | Related
Articles
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Rituximab therapy for follicular
lymphoma: a comprehensive review of it's efficacy as primary
treatment, treatment for relapsed disease, re-treatment and
maintenance - Yossi Cohen, et al PDF
| PDF-Help
|
Bone Marrow Purging with Rituxan
| Rituximab with peripheral
blood stem cell transplantation in CD20 lymphoproliferative
disorders
Patrizio Mazza, et al. - Haematologica.it
(2001)
"Bone marrow involvement in follicular center and mantle cell
lymphomas and chronic lymphocytic leukemia is difficult to
eliminate. Rituximab, an anti-CD20 specific therapy has been
demonstrated to be effective in marrow disease. We used rituximab
in combination with peripheral blood stem cell (PBSC)
transplantation following BEAM therapy in patients with CD20
positive marrow disease either in residual disease or as a purging
approach. Our experience emphasizes that the purging modality is
more effective than the treatment of residual disease."
|
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Novel Strategies in Treatment of MCL - Orion
M. Howard, M.D. and David Fisher, M.D. Northwestern Connecticut
Oncology and Hematology Associates, L. L. P., Torrington,
Connecticut 06790 mssm.edu
" Thirty-one patients had morphologic bone marrow
involvement and were therefore assessable for morphologic bone
marrow response. Twenty-one (68%) achieved a complete morphologic
response in the marrow."
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Rituxan & Bone Marrow Purging: Efficiency of in vivo purging with rituximab followed by
high-dose therapy (HDT) with autologous peripheral blood stem cell
transplantation (PBSCT) in B-cell lymphomas. A single institution
study. Year: 2002 Abstract No: 1139
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Combinations that May Enhance Rituxan?
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| ASCO 2003 - Increased potential cure for people with aggressive blood cancer -
Three-year follow-up data from GELA study shows greatly improved long term survival for aggressive non-Hodgkin's lymphoma patients treated with MabThera
eurekalert.org
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Combination chemotherapy and rituximab. Anticancer
Drugs. 2001 Jun;12 Suppl 2:S15-9. Review.
PMID: 11508932 PubMed
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Immunochemotherapy in indolent non-Hodgkin's lymphoma.
Semin Oncol. 2002 Apr;29(2 Suppl 6):11-7. Review. PMID:
12040529 PubMed
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Combination with Natural Product?
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Orally administered beta-glucans enhance anti-tumor effects of
monoclonal antibodies.
Cancer Immunol Immunother. 2002 Nov;51(10):557-64. Epub 2002 Sep 20. PMID:
12384807 | Related
abstracts
 | Beta-glucan, Complement action, and Rituxan clltopics.org
|
| Caveat? There is a theoretical concern about using
non-specific immune stimulants when you have lymphoma - a cancer
of lymphocytes (immune cells). See related and specific
articles that come to different conclusions about types of
immune cells stimulated by beta-glucans. Related
articles
 | Immunostimulant oxidized beta-glucan conjugates. Int
Immunopharmacol.
2001 Mar;1(3):539-50. PMID:
11367537
|
| Stimulation of humoral and cell mediated immunity by
polysaccharide from mushroom Phellinus linteus. Int J
Immunopharmacol. 1996 May;18(5):295-303. PMID:
8933208
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Consolidation / Maintenance Rituxan Treatment
Dosing and Treatment Cycle of Rituxan
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Optimal Schedule of Antibodies: Rituximab in Lymphoma as an
Example ASH 2005
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Prolonged
treatment with rituximab in patients with follicular lymphoma
significantly increases event-free survival and response duration
compared with the standard weekly x 4 schedule. Blood 2004;. PubMed
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| ASH 2002: Prolonged Rituximab Treatment Improves Event-Free Survival and Response Duration in Follicular
Lymphoma
Docguide.com
|
| Association of serum
Rituximab (IDEC-C2B8) concentration and anti-tumor response in the
treatment of recurrent low-grade or follicular non-Hodgkin's
lymphoma. Ann Oncol. 1998 Sep;9(9):995-1001.
PMID: 9818074 PubMed
(Note: Serum levels refers to concentration of the drug in the
blood.)
|
| Rituximab
dose-escalation trial in chronic lymphocytic leukemia. J Clin
Oncol. 2001 Apr 15;19(8):2165-70.
PMID: 11304768 PubMed
| Related
Abstracts
|
| Extended Rituximab (anti-CD20 monoclonal antibody) therapy
for relapsed or refractory low-grade or follicular non-Hodgkin's
lymphoma. Ann Oncol. 1999 Jun;10(6):655-61. PMID: 10442187 PubMed
|
Related
abstracts
|
| Rituximab chimeric anti-CD20 monoclonal antibody therapy for
relapsed indolent lymphoma: half of patients respond to a
four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. PMID:
9704735 PubMed
|
Predicting Response to Rituxan
| Efficacy of rituximab plus chemotherapy in follicular
lymphoma depends on Ki-67 expression.
Pathol Int. 2004 Sep;54(9):667-74. PMID:
15363034 | Related
articles
|
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Complement activation determines the therapeutic activity of
rituximab in vivo.
J Immunol. 2003 Aug 1;171(3):1581-7. PMID:
12874252 | Related
articles
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Predicting response to
Rituxan: Two Immunoglobulin G Fc Receptor Polymorphisms (expressed
on effector cells) Independently Predict Response in Pts With
Follicular NHL. J Clin Oncol. 2003 Sep 15 - PMID: 12975461
|
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Variation in gene expression patterns in follicular lymphoma and
the response to rituximab. Proc Natl Acad Sci U S A. 2003 Feb
18;100(4):1926-30.
PMID: 12571354 PubMed
|
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Genetic
characteristics (FCGR3A genotype) predict response to Rituxan?
Therapeutic activity of humanized anti-CD20 monoclonal antibody and
polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002 Feb
1;99(3):754-8. PMID: 11806974 PubMed
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Rituxan as First Line Treatment?
|
NEW: Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: A randomized phase II study from the Nordic Lymphoma Group.
Leuk Lymphoma. 2008 Jan;49(1):102-12. PMID: 18203019
Extended rituximab is effective and well tolerated and combination
with IFN seems to improve both the quality and duration of the
responses, providing the opportunity to achieve long-term molecular
CRs and prolonged failure-free survival without chemotherapy.
|
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Rituximab as first-line and
maintenance therapy for patients with indolent non-Hodgkin's lymphoma:
interim follow-up of a multicenter phase II trial. Semin Oncol. 2002
Feb;29(1 Suppl 2):25-9.
PMID: 11842385 PubMed
|
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Rituximab as first-line and maintenance therapy for patients with
indolent non-hodgkin's lymphoma.
J Clin Oncol. 2002 Oct 15;20(20):4261-7. PMID: 12377971 PubMed
|
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Rituximab as first-line systemic therapy for patients with
low-grade lymphoma.
Semin Oncol. 2000 Dec;27(6 Suppl 12):25-9. PMID:
11225997 PubMed
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Rituximab monoclonal antibody as initial systemic therapy for
patients with low-grade non-Hodgkin lymphoma. Blood.
2000 May 15;95(10):3052-6. PMID: 10807768 PubMed
|
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Low Tumor Burden: Rituximab (anti-CD20
monoclonal antibody) as single first-line therapy for patients with
follicular lymphoma with a low tumor burden: clinical and molecular
evaluation.
Blood. 2001 Jan 1;97(1):101-6.
PMID: 11133748 PubMed
|
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Frontline and Maintenance: Rituximab as First-Line
and Maintenance Therapy for Patients With Indolent Non-Hodgkin's
Lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. PMID: 12377971
PubMed
|
Mechanisms of Action (How Rituxan Might Work)
|
Unique Toxicities and Resistance Mechanisms Associated with
Monoclonal Antibody Therapy
Jonathan W. Friedberg asheducationbook.org
"Rituximab has multiple mechanisms of inducing in
vivo cytotoxicity, including antibody-dependent
cell-mediated cytotoxicity, complement-dependent cytotoxicity,
direct apoptotic signaling, and possible vaccinal effects."
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Signaling events involved in anti-CD20-induced apoptosis of
malignant human B cells. Cancer
Immunol Immunother. 2000
Mar;48(12):673-83. PMID: 10752475 PubMed
|
Rituxan Optimized with Biologics and Immune-based Therapies?
Interferon-alpha
| CpG ODN
| GM-CSF (Leukine)
Also see: Combination with other
antibodies | CHOP + Rituxan
| Modulating apoptosis pathways in low-grade B-cell malignancies
using biological response modifiers. (Rituxan, TRAIL, retinoid/steroid
family nuclear receptors, inhibitors of protein kinases.) T Semin
Oncol 2002 Feb;29 abstract
|
|
Research: Beyond immunochemotherapy: combinations of rituximab with
cytokines interferon-alpha2a and granulocyte-macrophage colony stimulating
factor. Semin Oncol. 2002 Apr;29(2 Suppl 6):7-10. Review. PMID: 12040528
PubMed
|
____________________
Interferon-alpha
From ASH
2000
Rituximab Plus Interferon-alpha in Low-Grade Lymphoma E. Kimby and
colleagues,[11] on behalf of The Nordic Lymphoma Group reported results obtained in 124
evaluable patients with follicular grade 1 or 2 CD20+ lymphoma who had received no prior
therapy (n = 90) or who had received no more than 6 months of chlorambucil or other such
therapy (n = 34). Treatment was not given unless patients were symptomatically in need.
All patients received 4 weekly doses of rituximab.
Patients who attained CR (11%) received no further therapy.
Patients who attained PR or minor response were then randomized to receive
either another 4 weeks of rituximab alone
or
weekly rituximab together with interferon-alpha, given at a dose of 3
MU/day for the first week and then 4.5 MU/day for weeks 2 through 5.
The response rate for interferon plus rituximab was 94% (48% CR), whereas that
for continued rituximab alone was 77% (22% CR).
In the combined interferon and rituximab group, grade 3 thrombocytopenia
occurred in 2 of 33 patients, with grade 4 neutropenia in 2 of 33. This study indicates
that the addition of interferon to rituximab is associated with an increased chance of
attaining an objective response, when compared with continued use of rituximab alone.
| NEW: Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: A randomized phase II study from the Nordic Lymphoma Group.
Leuk Lymphoma. 2008 Jan;49(1):102-12. PMID: 18203019
Extended rituximab is effective and well tolerated and
combination with IFN seems to improve both the quality and
duration of the responses, providing the opportunity to achieve
long-term molecular CRs and prolonged failure-free survival
without chemotherapy.
|
| Beyond immunochemotherapy:
combinations of rituximab with cytokines interferon-alpha2a and
granulocyte-macrophage colony stimulating factor. Semin Oncol. 2002
Apr;29(2 Suppl 6):7-10. Review. PMID: 12040528 PubMed
|
| Clinical activity and safety of combination immunotherapy with
IFN-alpha 2a and Rituximab in patients with relapsed low grade
non-Hodgkin's lymphoma. Haematologica. 2001 Sep;86(9):951-8.
PMID:
11532623 PubMed
|
| Combination immunotherapy of relapsed or refractory low-grade or
follicular non-Hodgkin's lymphoma with rituximab and
interferon-alpha-2a.
Clin Cancer Res. 2000 Jul;6(7):2644-52.
PMID: 10914705 PubMed
| Full
Text
|
____________________
CpG ODN
"We conclude that immunostimulatory CpG ODN can enhance
antibody dependent cellular cytotoxicity and warrant further evaluation as potential
immunotherapeutic reagents in cancer."
____________________
GM-CSF
 TOPIC
SEARCH - Medscape
| ASCO.org
| PubMed
|
Rituximab Activity Is Potentiated by GM-CSF in
Patients with Relapsed, Follicular Lymphoma: Results of a Phase II
Study. Session Type: Poster Session 636-II ASH
2005
Treatment of relapsed B-cell non-Hodgkin's lymphoma with a
combination of rituxan and G-CSF: final report on safety and
efficacy. Leukemia. 2003 Aug;17(8):1658-1664. PMID: 12886256
PubMed
| Related
abstracts
|
|
Antibody Dependent Cellular Cytotoxicity and Natural
Killer Cell Activity in Patients with Recurrent Indolent Lymphoma
Receiving Rituximab in Combination with GM-CSF. Session Type: Poster
Session 607-I - ASH [1495]
ASH 2003
|
|
Effect of GM-CSF, G-CSF or Methylprednisolone (MP) on
Rituximab-Associated Complement-Mediated Cytotoxicity (CMC) on
Non-Hodgkin’s Lymphoma (NHL) Cell Lines. ASCO
2001 # 1095
|
|
Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc
receptor-directed bispecific antibodies. J Immunol Methods. 2001 Feb
1;248(1-2):103-11. PMID: 11223072 PubMed
|
____________________
IL-12
"Objective
responses occurred in 29 of the 43 patients (69%), with 8 of 11 complete
responses seen at IL-12 doses of 300 ng/kg or greater. The optimal
immunologic dose of IL-12 in combination with rituximab was determined to
be 300 ng/kg
| Combination immunotherapy with rituximab and interleukin 2 in
patients with relapsed or refractory follicular non-Hodgkin's
lymphoma. Br J Haematol. 2002 Jun;117(4):828-34. PMID: 12060117 PubMed
|
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|
____________________
STEROIDS
|
Rituxan + steroids: Glucocorticoids and rituximab in vitro:
synergistic direct antiproliferative and apoptotic effects. Blood.
2002 Sep 1;100(5):1765-73. PMID: 12176898 PubMed
|
____________________
MISCELLANEOUS - other
biologics and agents that may synergize with Rituxan
|
Synergistic effects of the fenretinide (4-HPR) and anti-CD20
monoclonal antibodies on apoptosis induction of malignant human B
cells. Clin Cancer Res. 2001 Aug;7(8):2490-5.
PMID: 11489831 PubMed
The retinoid fenretinide (4-HPR): a non-toxic drug
related to Vitamin A
|
|
Dynavax Initiates First Human Trial Of ISS Immunotherapy And
Rituxin® (Rituximab) press
release
|
Treatment Indications - Conditions and Treatment Settings
TOPIC SEARCH: PubMed: Bulky
Disease | Retreatment
CLL
/ SLL | Cutaneous
follicular | Extranodal
and MALT | MCL
| Waldenstrom's
The future of determining who a treatment will benefit?
| Rituximab
maintenance therapy dramatically improves survival [at 3 years]
for patients
with lymphoma eortc.be
"Two years of maintenance therapy with rituximab
dramatically improves the chances of survival for patients
suffering from one of the most frequent forms of lymphoma,
indolent non-Hodgkin’s Lymphoma (NHL). The EORTC 20981 trial
reveals that rituxibam maintenance
treatment prolongs progression free
survival by about 2,5 years,
irrespective of initial treatment. Moreover, the risk of death is
halved for patients who receive rituximab
maintenance therapy, compared to those who receive no maintenance
treatment."
|
|
Drug response linked to genes in lymphoma patients GNN
"The researchers identified about 150 genes in lymph tumors that could help predict the drug response. The activity of these genes differed significantly between patients who responded to treatment and those who did not.
"
|
| Aggressive NHL: The role of rituximab and chemotherapy in aggressive B-cell
lymphoma: a preliminary report of dose-adjusted EPOCH-R. - Semin Oncol
2002 Feb;29 PubMed
|
|
Aggressive NHL: Phase II study of rituximab in combination with
chop chemotherapy in patients with previously untreated, aggressive
non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. PMID:
11208830 PubMed
|
| Aggressive NHL: The role of rituximab and chemotherapy in aggressive B-cell
lymphoma: a preliminary report of dose-adjusted EPOCH-R. - Semin Oncol
2002 Feb;29 abstract
|
| Bulky Disease: Single-agent monoclonal antibody efficacy in
bulky non-Hodgkin's lymphoma: results of a phase II trial of
rituximab. J Clin Oncol. 1999 Jun;17(6):1851-7.
PMID: 10561225 PubMed
| Jco.org
Full Text
|
| CLL: Rituxan & CLL published studies Genentech
|
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CLL: Rituximab and methylprednisolone
for therapy of CLL Year: 2002 Abstract No: 1923
|
|
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| Refractory NHL: Extended Rituximab (anti-CD20 monoclonal antibody) therapy for
relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma.
PubMed
|
|
Retreatment With: Re-treatment of relapsed indolent B-cell
lymphoma with rituximab.
Int J Hematol. 2001 Feb;73(2):213-21. PMID: 11372734
PubMed
|
|
Retreatment With: Rituximab anti-CD20 monoclonal antibody therapy
in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J
Clin Oncol. 2000 Sep;18(17):3135-43. PMID: 10963642 PubMed
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