cme-certified 2012 hematology tumor board series: practical solutions to current clinical challenges...
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CME-Certified 2012 Hematology Tumor Board Series: Practical Solutions to Current Clinical Challenges in T-Cell Lymphoma
CME-Certified 2012 Hematology Tumor Board Series: Practical Solutions to Current Clinical Challenges in T-Cell Lymphoma
ModeratorJames O. Armitage, MDJoe Shapiro Distinguished Chair of Oncology Professor of Internal MedicineDivision of Hematology/OncologyDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, Nebraska
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PanelistsJulie M. Vose, MD, MBA Neumann M. and Mildred E. Harris Professorial ChairChief and Professor of Internal Medicine Division of Hematology/OncologyDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, Nebraska
Bertrand Coiffier, MD, PhDProfessor of HematologyHead, Department of HematologyHospices Civils de LyonUniversité Claude BernardLyon, France
Owen O’Connor, MD, PhD Professor of Medicine and Developmental TherapeuticsColumbia University College of Physicians and SurgeonsDirector of the Center for Lymphoid MalignanciesNew York-Presbyterian HospitalColumbia University Medical CenterNew York, New York
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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.
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T-Cell LymphomaOverview
• 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.
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T-Cell LymphomaOverview
• 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.
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PTCL-NOSClinicopathologic 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
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AITLClinicopathologic 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)
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ALCLClinicopathologic 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
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Case 1PTCL-NOS
Case 1PTCL-NOS
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Case 1Presentation, 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.
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Case 1Additional 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.
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Case 1How Would You Approach
This Patient?
Case 1How Would You Approach
This Patient?
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T-Cell LymphomaSUVmax
Storto G, et al. Br J Haematol. 2010;151:195-197.
Extra-nodal
* †
SU
Vm
ax
181614121086420
T-Cell Indolent B-NHL
Aggressive B-NHL
Nodal
T-Cell Indolent B-NHL
SU
Vm
ax
181614121086420
*
B-NHL = B-cell non-Hodgkin lymphoma; SUVmax = maximum standardized uptake value.
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Case 1Initial 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
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PTCLDSHNHL Experience
EFS = event-free survival; LDH = lactate dehydrogenase; UNV = upper normal value.Schmitz N, et al. Blood. 2010;116:3418-3425.
EFS of Younger Patients (Aged 18-60 y; LDH Level < UNV)
Etoposide (n = 103)
Non-etoposide (n = 41)
Per
cen
tag
e o
f P
atie
nts
Months
100
90
80
70
60
50
40
30
20
10
00 10 20 30 40 50 60 70 80 90 100 110
P = .004
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PTCLUp-Front ASCT
ASCT = autologous stem cell transplant; OS = overall survival; PFS = progress-free survival.d’Amore F, et al. J Clin Oncol. 2012;30.3093-3099.
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Role of PET as Interim Prognostic Factor
Remains to be Clarified!
Role of PET as Interim Prognostic Factor
Remains to be Clarified!
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PTCL-NOSEuropean Perspective
PTCL-NOSEuropean Perspective
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PTCL-NOSAnthracycline-Based Chemotherapy
AbouYabis AN, et al. ISRN Hematol. 2011;2011:623924.
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PTCLSurvival Based on IPI Score
IPI = International Prognostic Index.Sonnen R, et al. Br J Haematol. 2005;129:366-3672.
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PTCL-NOSNovel Treatment Approaches
PTCL-NOSNovel Treatment Approaches
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Case 2ALCL
Case 2ALCL
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Case 2Presentation, 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.
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Case 2How Would You Approach
This Patient?
Case 2How Would You Approach
This Patient?
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Case 2Initial 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 high-dose 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.
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Aggressive LymphomaACVBP vs CHOP or HDT/ASCT
HDT = high-dose chemotherapy.Tilly H, et al. Blood. 2003;102:3418-3425.Gisselbrecht C, et al. J Clin Oncol. 2002;20:2472-2479.
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International T-Cell Lymphoma ProjectSubtypes and Clinical Outcomes
Vose J, et al. J Clin Oncol. 2008;26:4124-4130.
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Relapsed or Refractory ALCLTargeting CD30 With Ab-Drug Conjugate
Pro B, et al. J Clin Oncol. 2012;30:2190-2196.
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What if Patient Had ALCL, ALK+ Disease?
Use Standard CHOP-Based Chemotherapy.
What if Patient Had ALCL, ALK+ Disease?
Use Standard CHOP-Based Chemotherapy.
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Targeting ALKCrizotinib
Targeting ALKCrizotinib
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Novel AgentsPralatrexate
Novel AgentsPralatrexate
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Case 3AITL
Case 3AITL
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Case 3Presentation, 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.
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Case 3How Would You Approach
This Patient?
Case 3How Would You Approach
This Patient?
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O’Connor O, et al. J Clin Oncol. 2011;29:1182-1189.
Relapsed and Refractory PTCLPROPEL 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.
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CRu = complete remission unconfirmed.Coiffier B, et al. J Clin Oncol. 2012;30:631-636.
Relapsed and Refractory PTCLPhase 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
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Case 3Initial 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!
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AITLRole of Transplant
AITLRole of Transplant
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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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