Abstracts reporting on t-cell lymphomas at ASH 2010
Pralatrexate Is Effective In Patients with Relapsed or
Refractory Peripheral T-Cell Lymphoma (PTCL) with Prior Ifosfamide,
Carboplatin, and Etoposide (ICE)-Based Regimens
http://ash.confex.com/ash/2010/webprogram/Paper28321.html
Conclusions
Pralatrexate was highly active in patients with PTCL who received
prior ICE-based chemotherapy, with an ORR of 40% including CRs
leading to SCT in some patients. Of note, is the long duration of
pralatrexate responses in marked contrast to the short response
duration of the combination chemotherapy regimens. Taken together,
the efficacy of single-agent pralatrexate compared favorably with
ICE-based regimens, a finding that is consistent with other
exploratory analyses, showing that pralatrexate can reverse the
characteristic progressive resistance of PTCL patients to
second-line chemotherapy, and that pralatrexate is an effective
second-line treatment for patients with PTCL.
Final Results From a Pivotal, Multicenter, International,
Open-Label, Phase 2 Study of Romidepsin In Progressive or Relapsed
Peripheral T-Cell Lymphoma (PTCL) Following Prior Systemic Therapy
http://ash.confex.com/ash/2010/webprogram/Paper30063.html
Conclusions:
Complete and durable responses were observed with single agent
romidepsin in pts with relapsed PTCL. These data support the
therapeutic potential for romidepsin in relapsed PTCL and suggest
that romidepsin is a strong candidate for inclusion in future novel
regimens for these diseases.
Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4
Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL)
http://ash.confex.com/ash/2010/webprogram/Paper29172.html
Conclusions:
KW-0761 is a highly effective agent with acceptable toxicity
profiles in relapsed patients with CCR4-positive ATL who have no
standard therapies. A multicenter, randomized study for untreated
ATL patients to compare mLSG15 (a dose-intensified multi-agent
regimen, J Clin Oncol 2007;25:5458-64) + KW-0761 with mLSG15 alone
has been initiated.
Interim Results of a Phase 1 Trial of An Oral Histone Deacetylase
Inhibitor Belinostat In Patients with Lymphoid Malignancies (b or
t-cell)
http://ash.confex.com/ash/2010/webprogram/Paper33728.html
Conclusions: Oral Bel can be administered safely with a d
1-14, q3w schedule in pts with lymphoma at a daily dose higher than
what has been established for pts with solid tumors. Protocol
defined DLTs have been encountered in the dose range 750 – 2000mg in
pts with lymphoma. Cohort D at 1500 mg was expanded due to 1 DLT
(diarrhea). Cohort E at 1750 mg was tolerated without DLT and cohort
F 2000 mg is currently being investigated. Final evaluation will
include additional pts and possible dose escalation. The safety
profile and early tumor shrinkage noted in MCL and HD warrants
continued evaluation of Bel, especially in combination with other
active compounds.
Identification of An Active, Well-Tolerated Dose of
Pralatrexate In Patients with Relapsed or Refractory Cutaneous
T-Cell Lymphoma (CTCL): Final Results of a Multicenter Dose-Finding
Study
http://ash.confex.com/ash/2010/webprogram/Paper28381.html
Conclusions:
Pralatrexate shows high activity with acceptable toxicity in
patients with relapsed or refractory CTCL at the identified optimal
dose and schedule of 15 mg/m2 weekly for 3/4 weeks. The
lack of significant hematologic toxicity or cumulative toxicity seen
in this study suggests that pralatrexate should be further evaluated
as continuous or maintenance therapy for patients with CTCL. Final
efficacy and tolerability data will be reported.
The Prognosis of Limited Stage Peripheral T-Cell Lymphoma (PTCL):
A Population-Based Analysis and Comparison to Diffuse Large B-Cell
Lymphoma (DLBCL)
http://ash.confex.com/ash/2010/webprogram/Paper27282.html
Conclusion:
Limited stage cutaneous-only PTCL-NOS and ALK-pos ALCL as well as
selected patients with PTCL-NOS and ALK-neg ALCL with low risk
disease have a favourable prognosis. However, the prognosis remains
inferior to limited stage DLBCL. Despite an overall higher risk of
relapse, the cure rate is high in limited stage PTCL patients who
are able to receive a stem cell transplant as part of their salvage
therapy for relapsed or refractory disease.
Intensive Induction Chemotherapy Followed by Autologous Stem Cell
Transplantation (ASCT) In Patients with Enteropathy-Associated
T-Cell Lymphoma: a Prospective Study by the Nordic Lymphoma Group
(NLG-T-01)
http://ash.confex.com/ash/2010/webprogram/Paper27924.html
In this prospective study, intensive induction chemotherapy followed
by ASCT was feasible in the majority of younger patients with EATL.
In a subset of patients, who should clinically and
biologically be further characterized, long-term outcome seems
promising when compared to historical controls. Whether addition of
other chemotherapeutic agents, antibodies such as alemtuzumab or
other biologicals may further improve long-term outcome remains to
be studied.
The Novel Organic Arsenical, Darinaparsin (ZIO-101), Induces
Apoptosis through AKT and MEK/ERK Pathways In Hodgkin Lymphoma (HL)
and T-Cell Lymphoma (TCL) Cell Lines
http://ash.confex.com/ash/2010/webprogram/Paper32058.html
Conclusions:
Darninaparsin induces significant cell death in HL and TCL cell
lines that is mediated through AKT and MEK/ERK-based pathways.
Additionally, markedly higher intracellular darinaparsin levels are
achieved in lymphoma cells compared with equivalent concentrations
of ATO. Continued pre-clinical and clinical trial investigation of
darinaparsin in HL and TCL is warranted.
A Retrospective Analysis on Prognostic Factors of
Angioimmunoblastic T-Cell Lymphoma: a Multicenter Cooperative Study
In Japan
http://ash.confex.com/ash/2010/webprogram/Paper31134.html
[Conclusion] Prognosis of
patients with AITL in Japan is poor. Although IPI was useful in
prognostification of AITL, other factors including those not adopted
in IPI, such as IgA, anemia, TP and CRP, significantly affected the
prognosis in this analysis. Further validation studies of these
criteria should be performed.
Efficacy of Denileukin Diftitox Retreatment In Patients with
Cutaneous T-Cell Lymphoma Who Relapsed After Initial Response
http://ash.confex.com/ash/2010/webprogram/Paper31796.html
Conclusion:
Patients with CD25-positive CTCL who had been treated previously
with DD and subsequently relapsed were able to show durable
responses upon retreatment. The observed ORR of 40% was similar to
that seen with primary treatment with an estimated median duration
of response of 9.8 months.
Outcomes In Allogeneic Hematopoietic Stem Cell Transplantation
for Peripheral T-Cell Lymphoma: A Single Center's 12-Year Experience
http://ash.confex.com/ash/2010/webprogram/Paper31994.html
We conclude that allogeneic HSCT can provide durable
remission and survival for patients with relapsed and refractory
PTCL, with acceptable treatment-related mortality. Future
prospective trials are needed to further define the role of
allogeneic HSCT in this patient population.
The Combination of Histone Deacetylase Inhibitors and
Hypomethylating Agents Exhibits Marked Synergy In Preclinical Models
of T-Cell Lymphoma
http://ash.confex.com/ash/2010/webprogram/Paper31322.html
Collectively, the
data suggest that the combination of a hypomethylating agent like D
and a HDACI (B and R) are synergistic in in vitro models of
human T-cell lymphoma, and may lead to a new platform for the
treatment of these diseases.
Favorable Outcome In ALK-Negative Anaplastic Large-Cell Lymphoma
Following Intensive Induction Chemotherapy and Autologous Stem Cell
Transplantation (ASCT): a Prospective Study by the Nordic Lymphoma
Group (NLG-T-01)
http://ash.confex.com/ash/2010/webprogram/Paper27948.html
In ASCT eligible patients, intensive induction chemotherapy
consolidated by upfront ASCT is an effective treatment that yields
outcome results at least as good as those obtained in age-comparable
patients with diffuse large B-cell lymphoma.
Multicenter Phase II Study of the CyclOBEAP Regimen for Patients
with Peripheral T-Cell Lymphoma with Analysis of Biomakers
http://ash.confex.com/ash/2010/webprogram/Paper27395.html
Our results suggest that the CyclOBEAP therapy is safe and
effective for the treatment of PTCLs. Furthermore, nm23-H1 protein
expression may be an important prognostic factor in PTCLs.
Aplidin® (Plitidepsin) Activity In Peripheral T-Cell
Lymphoma (PTCL): Final Results
http://ash.confex.com/ash/2010/webprogram/Paper29970.html
Conclusions Plitidepsin has activity, with an
acceptable safety profile in non-cutaneous relapsed/refractory PTCL
patients. Remarkably, lack of hematologic toxicity makes plitidepsin
an ideal agent either for treating patients with poor bone marrow
reserve or combining it with other active agents. A combination of
plitidepsin with gemcitabine is currently being explored in this
patient population.
Low Absolute Lymphocyte Count Predicts Chemotherapy Response and
Survival In Peripheral T-Cell Lymphoma, NOS
http://ash.confex.com/ash/2010/webprogram/Paper34796.html
This study suggested that low ALC is an independent
prognostic factor for survival in patients with PTCL, NOS.
Addition of Anti-Viral Therapy to Chemotherapy Improves Overall
Survival In Acute and Lymphomatous Adult T-Cell Leukaemia/Lymphoma (ATLL)
http://ash.confex.com/ash/2010/webprogram/Paper33893.html
Conclusions Our results point to the benefit of
treatment with ZDV/IFN at some stage, given the failure of any
patient to survive 2 years in the absence of this therapy. In the
recent meta-analysis insufficient patient numbers with lymphoma were
treated with adjunctive ZDV/IFN therapy to demonstrate any benefit,
whilst first line therapy with ZDV/IFN alone was ineffective.
However, we have documented significant clinical benefit from the
addition of ZDV/IFN to chemotherapy in lymphomatous ATLL. Together
these two studies suggest the following treatment approach to
improve outcome in aggressive ATLL: Acute type– 1st line
treatment with AZT/IFN alone. Lymphomatous type - 1st line treatment
with chemotherapy and early addition of ZDV/IFN. This is a major
step forward in ATLL therapy, but it is important to recognise that
some patients will fail therapy and overall survival remains poor.
Smouldering Adult T-Cell Leukaemia/Lymphoma (ATLL) Is Not Associated
with An Increased Risk of Aggressive ATLL In HTLV-1 Positive
Patients
http://ash.confex.com/ash/2010/webprogram/Paper33261.html
In this cohort fulfilment of the Shimoyama classification for
smouldering ATLL was not associated with an increased risk of
developing aggressive ATLL (1/43 v 2/107) during a median of 3.7
years of follow up. We therefore propose that ATLL should not be
diagnosed in the absence of a raised lymphocyte count and/or organ
involvement. However HTLV-1 proviral load does appear to be an
important predictor for risk of ATLL and further study to identify
patients at risk prior to development of this aggressive malignancy
is warranted.
Enteropathy-Associated T-Cell Lymphoma: a Clinical Prognostic Model
to Identify High Risk Patients
http://ash.confex.com/ash/2010/webprogram/Paper27032.html
In conclusion, our new prognostic model clearly identifies a
high and a low risk group. Patients with one or more of the risk
factors serum LDH > normal, B-symptoms or subtype secondary EATL are
at high risk, and therefore new therapies for this group are
urgently needed.
Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide,
Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage
I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx
http://ash.confex.com/ash/2010/webprogram/Paper29701.html
Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be
an effective treatment strategy with acceptable toxicity in stage
I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx.
Sufficient and Timely Autologous Stem Cell Harvest After
Chemoimmunotherapy with Alemtuzumab In Combination with Bi-Weekly
CHOP as First Line Treatment In Systemic Peripheral T-Cell Lymphomas
(PTCL): a Feasibility Analysis From the First Randomized Trial In
Systemic PTCL (ACT trial)
http://ash.confex.com/ash/2010/webprogram/Paper31012.html
In conclusion, the addition of alemtuzumab to bi-weekly CHOP
in the setting of first-line therapy of primary systemic PTCL does
not significantly impair ASCH (autologous stem cell harvest ) prior
to upfront autologous stem cell transplant.
Long-Term Outcome for De Novo Lymphoblastic Lymphoma (LL) After
Frontline Therapy with Hyper-CVAD Regimen and Variants
http://ash.confex.com/ash/2010/webprogram/Paper33894.html
An augmented hyper-CVAD regimen (dose intensifying VCR/dexamethasone
components and incorporating pegylated asparaginase) has been
successfully piloted in the salvage setting. The optimal first line
chemotherapy of LL continues to be refined; the role of autologous
or allogeneic SCT for LL in first CR remains unclear since majority
of patients can be cured without use of these modalities.
Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4
Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL)
http://ash.confex.com/ash/2010/webprogram/Paper29172.html
Conclusions: KW-0761 is a highly effective agent
with acceptable toxicity profiles in relapsed patients with
CCR4-positive ATL who have no standard therapies. A multicenter,
randomized study for untreated ATL patients to compare mLSG15 (a
dose-intensified multi-agent regimen, J Clin Oncol 2007;25:5458-64)
+ KW-0761 with mLSG15 alone has been initiated.
Gemcitabine, Ifosfamide, Oxaliplatin (GIFOX) as First-Line Treatment
In High-Risk Peripheral T-Cell/NK Lymphomas: A Phase II Trial
http://ash.confex.com/ash/2010/webprogram/Paper33733.html
Conclusions:
GIFOX retains an attractive
therapeutic potential as upfront strategy in PTCL, enabling
cytoreduction and SCs mobilization for ASCT consolidation, and
allows the safe delivery of a full induction program also to
patients aged or unfit for high dose therapy.
Response Rate of 16% and High Incidence of Adverse Events In
Placebo-Treated Patients with CD25 Assay-Positive Cutaneous T-Cell
Lymphoma (CTCL): An Analysis of Patient Characteristics and
Predictors of Response
http://ash.confex.com/ash/2010/webprogram/Paper32102.html
Conclusion: The findings from this study demonstrate that
responses can be observed in patients with MF/SS in the absence of
anti-tumor treatment. Likely contributing factors to these
‘spontaneous responses’ are the use of systemic antibiotics,
aggressive ‘rescue medication’ use and the waxing and waning nature
of skin lesions, particularly in early-stage disease. All future
studies should carefully document the use of systemic antibiotics
during therapy. These results can serve as standard comparators for
other active-treatment studies that lack a placebo control arm.
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