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R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature
pubmedcentral.nih.gov
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ASCO 2009: Expert Video Perspective on Lymphoma James O.
Armitage, MD medscape.com/
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| Study Suggests New
First-line Treatment Option for Follicular Lymphoma cancer.gov
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| Updated Phase II Results With Radiolabeled
Epratuzumab in Non-Hodgkin's Lymphoma drugs.com
n = 62
The overall objective response rate (partial and complete
responses) in 62 evaluable patients was 64%, with 49% of patients
having a complete response. Both the objective and complete
response rates appear to correlate with cumulative doses. In 16
patients unresponsive to last therapy, 75% responded to Y-90
epratuzumab tetraxetan with 56% complete responses. More
importantly, responses were seen across all different types of
NHL.
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Understanding
Clinical Trial Design: PDF A Tutorial for Research Advocates
Authored by Jane Perlmutter, PhD
for Research Advocacy Network’s Advocate Institute
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Allogeneic stem cell transplantation in children and
adolescents with recurrent and refractory Hodgkin's lymphoma
Claviez A, Canals C, Dierickx D, Stein J, Badell I, Pession A,
Mackinnon S, Slavin S, Dalle JH, Jurado Chacon M, Sarhan M, Wynn
RF, Suttorp M, Dini G, Sureda A, Schmitz N.
Blood. 2009 Jun PMID:
19498021
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ABT-263 activity and safety in patients with relapsed or
refractory lymphoid malignancies in particular chronic lymphocytic
leukemia (CLL)/small lymphocytic lymphoma (SLL).
http://www.abstract
.asco.org/
AbstView_
65_30712.
html
ABT-263 showed favorable PK and safety profiles
with anti-tumor activity in relapsed/refractory CLL/SLL and
follicular lymphoma. Identification of optimal dose and schedule
for phase II trials continues.
 ABT-263 studies
recruiting: ClinicalTrials.gov
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Comparing R-CHOP 14 and R-CHOP 21 for the treatment of
patients with newly diagnosed DLBCL.
n = 1,080 randomized to CHOP-R x14 (dose dense
schedule) vs. CHOP-R 21 day schedule
Comment: Very encouraging overall results: 2-year failure-free survival rate for the
entire cohort of 74% . Important study because of the size (n >1,000) and that it was randomized.
Curious that the protocols compared were not given with an equal number of
rounds? x6 vs. x8. Small increased trend in cardiac toxicity with dose dense CHOP-R x 6
- 2% vs 0.4%
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| The "autophagy pathway" could be a very important nut to crack,
so it bears watching. http://www.ncbi.nlm.nih.gov/pubmed/19216910
This pathway appears to shut down treatment-stressed cells so that they survive in a dormant-like state, or in hypoxic (low oxygen) conditions.
This cell survival pathway might explain resistance to Rituxan http://www.abstract.asco.org/AbstView_65_33619.html
For technical background on autophagy, Autophagy in Cancer: Good, Bad, or Both?:
http://cancerres.aacrjournals.org/cgi/content/full/66/19/9349
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| Idiotype vaccine therapy (BiovaxID) in follicular lymphoma
in first complete
remission: Phase III clinical trial results. abstract
.asco.org
n = 234 pts enrolled; 177 (76%) achieved CR/CRu
and were randomized.
Of 177 randomized pts, 117 maintained CR/CRu ≥ 6 mo per
protocol requirement and then received at least one dose of
vaccine, 55 relapsed before vaccination, 4 were vaccine
manufacturing failures, and 1 violated protocol.
Comment: This report from a controlled study
appears to support that idiotype vaccines are active and have the
potential to provide meaningful clinical benefit. However,
this analysis is for a "modified
intent-to-treat population" ... representing roughly half of
the patients who started in the study, and these outcomes with
PACE and vaccine may not compare well with Rituxan-based
chemotherapy, the new standard of care. So the key going
forward will be if the improvement in outcomes can be reproduced
following Rituxan-based chemo.
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| Progressive multifocal leukoencephalopathy [PML] after
Rituxan therapy in HIV-negative patients: a report of 57 cases
from the Research on Adverse Drug Events and Reports project
bloodjournal.hematologylibrary.org
In conclusion, rituximab administration may
increase risks of developing PML, although the absolute
risk of developing PML is probably low. As use of
rituximab expands to diverse clinical settings,
clinicians and patients should be aware of the potential for
PML after rituximab therapy. Awareness and reporting of rituximab-associated
PML cases to the FDA are essential to improve our
understanding of risk factors, natural course, and alternative
therapeutic approaches. Despite widespread public health
advisories describing 2 patients with SLE and 1 patient
with rheumatoid arthritis who were diagnosed with
rituximab-associated PML, we identified 22 previously
unreported cases associated with lymphoid malignancies
and immunologically mediated cytopenias. Early
diagnosis of PML will prompt efforts at immune reconstitution,
which may be beneficial in improving survival rates.
Finally, early diagnosis before irreversible neurologic
damage has occurred will be crucial for evaluation of
the efficacy of new antiviral treatments.
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Efficacy and tolerability of currently available therapies for
the mycosis fungoides and Sezary syndrome variants of cutaneous
T-cell lymphoma. Whittaker SJ, Foss FM. Cancer Treat Rev. 2007
Apr;33(2):146-60. Epub 2007 Feb 1. Review. PMID:
17275192
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| Efficacy of lenalidomide (Revlimid) oral monotherapy in
relapsed or refractory indolent NHL:
Final results of NHL-001. abstract.asco.org
Oral lenalidomide monotherapy can produce durable
responses with manageable side effects in relapsed or refractory
indolent NHL
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| Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma
(sALCL). abstract.asco.org
SGN-35 was generally well tolerated and induced CRs
in 7 of 8 evaluable pts at the two highest doses in heavily
pretreated patients. Pivotal trials of this antibody-drug
conjugate will initiate in early 2009.
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| YM155 shows activity in relapsed and refractory DLBCL. abstract.asco.org
Targets Survivin - inhibitor of apoptosis proteins
(IAPs)
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Additional Evidence That Antibiotics Are Effective Against
Gastric MALT Lymphomas http://patient.cancerconsultants.com
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Rituximab Maintenance for the Treatment of Patients With
Follicular Lymphoma: Systematic Review and Meta-analysis of
Randomized Trials medscape.com
(free login req.)
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Phase I Trial of Daily Oral Polyphenon E in
Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic
Leukemia
http://jco.ascopubs.org/cgi/content/short/JCO.2008.21.1284v1?rss=1
Epigallocatechin-3-gallate (EGCG) was administered
using the standard phase I design with three to six patients per
dose level (range, 400 to 2,000 mg by mouth twice a day).
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The Sponsor and FDA are negotiating an indication
statement for ARZERRA (ofatumumab) in the treatment of chronic
lymphocytic leukemia (CLL) under the provisions of accelerated
approval based on studies that have investigated response rate, a
surrogate endpoint for clinical benefit.
Briefing documents:
Advisory board:
http://www.fda.
gov/ohrms/
dockets/ac/
09/briefing/
2009-4444b1-
01-FDA.pdf
GSK:
http://www.fda.
gov/ohrms/
dockets/ac/
09/briefing/
2009-4444b1-
02-GSK.pdf
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Wrong Way in the War on Cancer alternet.org
"The result is that many of the nation’s
30,000 oncologists are engaged in what could be described as an
unobserved and uncontrolled science experiment, especially when it
comes to treating the 560,000 Americans who die each year from the
more than 100 forms of the disease. As these patients’ cancers
advance, their physicians try regimens they read about in journals
or hear about from colleagues. The outcomes are never gathered.
The data is never analyzed. And the findings are never
disseminated."
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[Rituxan] Linked To Often Fatal Brain Virus [PML] sciencedaily.com
"But concerns about the drug's association
with PML first surfaced in 2006 when two patients with lupus
developed the illness after taking rituximab and other
immunosuppressive treatments."
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Study Shows Disruption Of Immune-System Pathway Key Step In
Cancer Progression medicalnewstoday.com
"Silencing an inter-cell signaling mechanism
called the interferon pathway may be one way newly developing
cancers gain the upper hand. It may also explain the immune
dysfunctions seen in many cancer patients and why cancer
immunotherapies are often ineffective."
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Two Targeted Therapies (Rituxan and Epratuzumab) Yields Very
Good Results in Patients with Aggressive Lymphoma bio-medicine.org/
researchers say that adding the targeted
therapy epratuzumab to a regimen known as R-CHOP resulted in an
overall 12-month survival of 88 percent in 78 patients. While they
call that a very good outcome, the researchers were especially
encouraged because the survival rate was 85 percent in patients
with high-risk disease.
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Technical and preclinical: Ribavirin (anti-viral drug)
suppresses eIF4E-mediated oncogenic transformation
2004 Dec 15. PMID:
15601771
Ribavirin and its derivatives offer a
pharmacologic means to interrupt networks of tumor suppressors and
oncogenes that maintain and enhance neoplasia and malignancy.
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Vaccine Concept: Recognition of live labeled tumor cells by
dendritic cells: a novel approach to immunotherapy of skin cancer.
Shurin MR, Potapovich AI, Tyurina YY, Tourkova IL, Shurin GV,
Kagan VE. Cancer
Res. 2009 Mar 15;69(6):2487-96. Epub 2009 Mar 10. PMID:
19276376
Dendritic cells (DC) loaded with tumor antigens
from apoptotic/necrotic tumor cells are commonly used as vaccines
for cancer therapy. However, the use of dead tumor cells may cause
both tolerance and immunity, making the effect of vaccination
unpredictable. To deliver live tumor "cargoes" into DC,
we developed a new approach based on the "labeling" of
tumors with a phospholipid "eat-me" signal,
phosphatidylserine.
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Highly increased familial risks for specific lymphoma
subtypes.
Goldin LR, Björkholm M, Kristinsson SY, Turesson I, Landgren O. Br
J Haematol. 2009 May 4. PMID:
19438470
Relatives were at the highest risk for
developing the same lymphoma subtype as the case. DLBCL was
increased 10-fold among relatives of DLBCL patients, FL was
increased fourfold among relatives of FL patients and HL was
increased fourfold among relatives of HL patients. These results
imply that germline susceptibility genes are specific to lymphoma
subtype.
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Home Diet and Exercise May Benefit
Long-Term Cancer Survivors oncologystat.com
A home-based diet and exercise program reduced the
rate of functional decline in a study of more than 600 overweight
and older cancer survivors, according to a report in the May 13
issue of JAMA.
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Ginger Eases Nausea From Chemo healthday.com
Participants were randomized to receive either a
placebo or one of three doses of ginger supplement: 0.5 grams, 1
gram or 1.5 grams for three days before the start of chemo and
three days after for the next two cycles. All also received
traditional antiemetic drugs on the first day of treatment.
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Placebo-Controlled Phase III Trial of Patient-Specific
Immunotherapy With Mitumprotimut-T (Fav-Id) and
Granulocyte-Macrophage Colony-Stimulating Factor After Rituximab
in Patients With Follicular Lymphoma.
J Clin Oncol. 2009 May 4 PMID:
19414675
TTP was shorter with mitumprotimut-T/GM-CSF
compared with placebo/GM-CSF. This difference was possibly due to
the imbalance in FLIPI scores.
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Genetic variation in caspase genes and risk of NHL: a pooled
analysis of three population-based case-control studies. Blood.
2009 May 4. PMID:
19414860
"It is noteworthy that genetic variants in
CASP8 were associated with risk of all major NHL subtypes. Our
findings suggest that genetic variation in caspases may play an
important role in lymphomagenesis."
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Late-onset neutropenia (LON) following RCHOP chemotherapy in
diffuse large B-cell lymphoma
Am
J Hematol. 2009 Mar 31. PMID:
19415727
"it is reassuring that LON is self-limiting
and unassociated with life-threatening infection. A watchful
waiting approach is appropriate in majority of patients who
develop LON following RCHOP.
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Extranodal marginal zone lymphoma of the ocular adnexa bloodjournal.hematologylibrary.org
"Besides radiotherapy and
chemotherapy, a variety of new treatment options have emerged
in the management of patients with ocular adnexal MALT
lymphoma, especially monoclonal antibody therapy and
antibiotic therapy against Chlamydia psittaci, which
has been associated with the pathogenesis of ocular
adnexal lymphomas in some parts of the world. In this
review, we are presenting a state of the art summary on
ocular adnexal MALT lymphomas."
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Diffuse large B-cell lymphoma: reduced CD20 expression is
associated with an inferior survival bloodjournal.hematologylibrary.org
"In conclusion, we have demonstrated that
discordant CD20 expression by FCM (flow cytometry)
using diagnostic DLBCL biopsies may be a novel biomarker that
could identify a subgroup of high-risk patients treated with
R-CHOP. Moreover, this biomarker could be identified using flow
cytometry, a technique that is already used in most clinical laboratories.
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A Phase I Study of a Bispecific Chain Immunotoxin for the Treatment of CD19(+), CD22 (+) B-Lineage Leukemia or Lymphoma
ClinicalTrials.gov
"Immunotoxins, such as DT2219ARL, can find certain cancer cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of DT2219ARL immunotoxin in treating patients with B-cell leukemia or lymphoma that has relapsed or not responded to treatment."
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PERSPECTIVE: A re-examination of radioimmunotherapy in the
treatment of NHL: prospects for dual-targeted antibody/radioantibody
therapy Robert M. Sharkey1, Oliver W. Press2, and David M.
Goldenberg1 bloodjournal.hematologylibrary.org
Discusses potential of clearing normal b-cells with
non-competing antibody to optimize the effect of the radiolabeled
antibody - so that all the cd20 receptors are available to the
"hot" antibody. Also discusses fractionated dosing to
improve safety without compromising efficacy.
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