T-Cell Lymphoma SUV max

Report
CME-Certified 2012 Hematology
Tumor Board Series: Practical
Solutions to Current Clinical
Challenges in T-Cell Lymphoma
Moderator
James O. Armitage, MD
Joe Shapiro Distinguished Chair of Oncology
Professor of Internal Medicine
Division of Hematology/Oncology
Department of Internal Medicine
University of Nebraska Medical Center
Omaha, Nebraska
Panelists
Julie M. Vose, MD, MBA
Bertrand Coiffier, MD, PhD
Neumann M. and Mildred E. Harris
Professorial Chair
Chief and Professor of Internal Medicine
Division of Hematology/Oncology
Department of Internal Medicine
University of Nebraska Medical Center
Omaha, Nebraska
Professor of Hematology
Head, Department of Hematology
Hospices Civils de Lyon
Université Claude Bernard
Lyon, France
Owen O’Connor, MD, PhD
Professor of Medicine and Developmental Therapeutics
Columbia University College of Physicians and Surgeons
Director of the Center for Lymphoid Malignancies
New York-Presbyterian Hospital
Columbia University Medical Center
New York, New York
Program Goals
• Identify prognostic and clinical factors that
should be considered in selecting treatment
for patients with T-cell lymphoma.
• Consider patient- and disease-specific factors
when selecting frontline and
relapse/refractory treatment options for
patients with T-cell lymphoma.
• Assess how emerging therapies or regimens
for patients with T-cell lymphoma may impact
current treatment practices.
T-Cell Lymphoma
Overview
• Relatively rare
− ~10% of lymphomas in the United States
• PTCL
− Arises from mature T-cell counterparts
− Geographic variation in distribution
− Has 3 major aggressive subtypes
• PTCL-NOS (25.9%)
• AITL (18.5%)
• ALCL (ALK+[6.6%], ALK−[5.5%])
AITL = angioimmunoblastic T-cell lymphoma; ALCL = anaplastic large cell lymphoma; ALK =
anaplastic lymphoma kinase; NOS = not otherwise specified; PTCL = peripheral T-cell lymphoma.
Vose J, et al. J Clin Oncol. 2008;26:4124-4130.
T-Cell Lymphoma
Overview
• Relatively rare
− ~10% of lymphomas in the United States
• PTCL
− Arises from mature T-cell counterparts
− Geographic variation in distribution
− Has 3 major aggressive subtypes
• PTCL-NOS (25.9%)
• AITL (18.5%)
• ALCL (ALK+[6.6%], ALK−[5.5%])
AITL = angioimmunoblastic T-cell lymphoma; ALCL = anaplastic large cell lymphoma; ALK =
anaplastic lymphoma kinase; NOS = not otherwise specified; PTCL = peripheral T-cell lymphoma.
Vose J, et al. J Clin Oncol. 2008;26:4124-4130.
PTCL-NOS
Clinicopathologic Features
• Clinically aggressive, typically occurs in adults
aged 50 to 70 years
− Usual patient presentation: high-stage disease,
generalized lymphadenopathy, B symptoms, and
peripheral blood eosinophilia
• Highly variable pathology
− Most likely represents more than 1 subtype
• Broad differential diagnosis due to the
heterogeneous appearance
− Other lymphoma subtypes
− Reactive hyperplasias due to viral or drug reaction
AITL
Clinicopathologic Features
• Clinically aggressive, typically occurs in middle-aged
or elderly adults
− Dismal outcome with current therapies
− Usual patient presentation: generalized lymphadenopathy,
fever, weight loss, skin rashes, arthritis, polyclonal
hypergammaglobulinemia, and hemolytic anemia
• Displays a characteristic arborizing vascular pattern
• Coexisting immune dysfunction may complicate
diagnosis.
• Differential diagnosis
− Other lymphoma subtypes
− Atypical immune reaction
− Hyperplasia (viral or idiopathic)
ALCL
Clinicopathologic Features
• Clinically aggressive with biphasic age
distribution
− Younger patients, generally ALK+
• Associated with improved survival compared with
other PTCL subtypes
− Older patients, more likely ALK−
• Not challenging to identify
− CD30 strongly expressed in all cases
− t(2;5)(p23;q25), prototypical translocation in ALK+
subtype
• Abnormal ALK-NPM fusion protein overexpressed
Case 1
PTCL-NOS
Case 1
Presentation, Biopsy, PET/CT Scan
• A 50-year-old man presented with fatigue
and lymphadenopathy.
• Biopsy showed PTCL-NOS.
• Patient underwent PET/CT scanning,
which showed
− Nodes in the axilla, periaortic region, and
iliac region; and
− An SUVmax of 9.
SUVmax = maximum standardized uptake value.
Case 1
Additional Findings
• His spleen was slightly enlarged with no
focal lesions.
• Results of a CBC were normal, except for
his platelet count, which was 135,000/mm3.
• Results of a bone marrow biopsy were
negative.
• Remaining results from the diagnostic
work-up were negative.
Case 1
How Would You Approach
This Patient?
T-Cell Lymphoma
SUVmax
Nodal
18
16
14
12
10
8
6
4
2
0
SUVmax
SUVmax
Extra-nodal
*†
T-Cell
Indolent
B-NHL
Aggressive
B-NHL
18
16
14
12
10
8
6
4
2
0
*
T-Cell
Indolent
B-NHL
B-NHL = B-cell non-Hodgkin lymphoma; SUVmax = maximum standardized uptake
value.
Storto G, et al. Br J Haematol. 2010;151:195-197.
Case 1
Initial Treatment Considerations
• As a relatively young and fit patient, he
should be given aggressive therapy.
− Consider an etoposide-containing regimen.
• Consider ASCT as consolidation after
induction therapy.
• Always try to enroll a patient in clinical trial,
if possible.
CHOP not effective
PTCL
DSHNHL Experience
EFS of Younger Patients (Aged 18-60 y; LDH Level < UNV)
100
Percentage of Patients
90
80
Etoposide (n = 103)
70
60
50
40
Non-etoposide (n = 41)
30
20
P = .004
10
0
0
10
20
30
40
50
60
70
80
90 100 110
Months
EFS = event-free survival; LDH = lactate dehydrogenase; UNV = upper normal value.
Schmitz N, et al. Blood. 2010;116:3418-3425.
PTCL
Up-Front ASCT
IMAGE NO LONGER AVAILABLE
ASCT = autologous stem cell transplant; OS = overall survival; PFS = progress-free survival.
d’Amore F, et al. J Clin Oncol. 2012;30.3093-3099.
Role of PET as Interim
Prognostic Factor
Remains to be Clarified!
PTCL-NOS
European Perspective
PTCL-NOS
Anthracycline-Based Chemotherapy
AbouYabis AN, et al. ISRN Hematol. 2011;2011:623924.
PTCL
Survival Based on IPI Score
IPI = International Prognostic Index.
Sonnen R, et al. Br J Haematol. 2005;129:366-3672.
PTCL-NOS
Novel Treatment Approaches
Case 2
ALCL
Case 2
Presentation, Biopsy, PET/CT Scan
• A 41-year-old man presented with fever
38.5oC) and malaise and was found to have
a palpable right axillary node.
• A biopsy of the axillary node showed ALCL,
CD30+ and ALK−.
• Results of a bone marrow biopsy were
negative.
• He underwent PET/CT scanning, which
showed PET-avid enlarged nodes in the
chest and abdomen.
Case 2
How Would You Approach
This Patient?
Case 2
Initial Treatment Considerations
• Given that it is stage III disease, ALCL,
ALK−, it should be approached as if it
were PTCL-NOS rather than ALCL,
ALK+.
• He is young and may tolerate the highdose combination very well.
− Treatment options include ACVBP* with
supportive G-CSF, CHOEP, or EPOCH.
• If he reaches CR → ASCT.
* Regimen not available in the United States.
Aggressive Lymphoma
ACVBP vs CHOP or HDT/ASCT
IMAGE NO LONGER AVAILABLE
HDT = high-dose chemotherapy.
Tilly H, et al. Blood. 2003;102:3418-3425.
Gisselbrecht C, et al. J Clin Oncol. 2002;20:2472-2479.
International T-Cell Lymphoma Project
Subtypes and Clinical Outcomes
IMAGE NO LONGER AVAILABLE
Vose J, et al. J Clin Oncol. 2008;26:4124-4130.
Relapsed or Refractory ALCL
Targeting CD30 With Ab-Drug Conjugate
IMAGE NO LONGER AVAILABLE
Pro B, et al. J Clin Oncol. 2012;30:2190-2196.
What if Patient Had ALCL,
ALK+ Disease?
Use Standard CHOP-Based
Chemotherapy.
Targeting ALK
Crizotinib
Novel Agents
Pralatrexate
Case 3
AITL
Case 3
Presentation, Biopsy, PET/CT Scan
• A 70-year-old women presented with a macular
rash, pruritus, drenching night sweats, 10-lb
weight loss, and widespread lymphadenopathy.
• Biopsy results showed AITL.
• Results of a bone marrow biopsy were positive.
• A CBC found anemia (Hb 10 g/dL), and the
Coombs was negative.
• PET/CT scanning revealed widespread enlarged
nodes above and below the diaphragm.
CBC = complete blood count; Hb = hemoglobin.
Case 3
How Would You Approach
This Patient?
Relapsed and Refractory PTCL
PROPEL Trial
Subtype
IWC Response Rates, %
CI, 95%
PTCL-NOS (n = 59)
32
21-46
AITL (n = 13)
8
0-36
ALCL (n = 17)
35
14-62
IWC = International Workshop Criteria.
O’Connor O, et al. J Clin Oncol. 2011;29:1182-1189.
Relapsed and Refractory PTCL
Phase 2 Study of Romidepsin
Subtype
CR/CRu, %
ORR, %
PTCL-NOS (n = 69)
14
29
AITL (n = 27)
19
30
ALCL, ALK− (n = 21)
19
24
CRu = complete remission unconfirmed.
Coiffier B, et al. J Clin Oncol. 2012;30:631-636.
Case 3
Initial Treatment Considerations
• Patients like this—older and not very well—often
respond early on to steroids.
− Start with a steroid-containing combination to try to get her
symptoms under control and improve her performance status.
• Avoid anthracycline-based therapy.
• Single-agent gemcitabine may help manage disease
without excess myelosuppression.
• Look for the possible presence of an associated B-cell
clone; if found, use a rituximab combination.
• This is one of the more difficult patient types.
• If possible, enroll the patient in clinical trial!
AITL
Role of Transplant
Concluding Remarks
• The key to getting a better understanding
of these rare lymphoma subtypes and to
improving patient outcomes lies in a
collaborative effort and efficient enrollment
of patients into clinical trials.
• We also need more biologic studies to
discern and understand clinicopathologic
features of various PTCL subtypes better.

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