copyright © 2010, research to practice, all rights reserved. part vii: mantle-cell lymphoma, t-cell...
Post on 02-Jan-2016
220 Views
Preview:
TRANSCRIPT
Copyright © 2010, Research To Practice, All rights reserved.
Part VII: Mantle-Cell Lymphoma, T-Cell Lymphomas, Diffuse Large B-Cell Lymphoma Monday, November 1, 20107:30 PM - 8:30 PM ET
Monday Night with Research To Practice: An 8-Part Live CME Webcast Series
Steven M Horwitz, MDAssistant AttendingLymphoma Service, Division of Hematologic OncologyMemorial Sloan-Kettering Cancer CenterNew York, New York
Mitchell R Smith, MD, PhDDirector, Lymphoma ServiceFox Chase Cancer CenterPhiladelphia, Pennsylvania
Neil Love, MDModeratorResearch To PracticeMiami, Florida
Disclosures for Moderator Neil Love, MD
Dr Love is president and CEO of Research To Practice, which receives funds in the form of educational grants to develop CME activities from the following commercial interests: Abraxis BioScience Inc, a wholly owned subsidiary of Celgene Corporation, Allos Therapeutics, Amgen Inc, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cephalon Inc, Eisai Inc, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, Lilly USA LLC, Millennium Pharmaceuticals Inc, Myriad Genetics Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Sanofi-Aventis and Spectrum Pharmaceuticals Inc.
Consulting Agreements
Allos Therapeutics, Celgene Corporation, Millennium Pharmaceuticals Inc
Paid ResearchAllos Therapeutics, Genzyme Corporation
Disclosures for Steven M Horwitz, MD
Advisory Committee Cephalon Inc, Wyeth
Speakers Bureau
Allos Therapeutics, Celgene Corporation, Cephalon Inc, Genentech BioOncology, Millennium Pharmaceuticals Inc, Spectrum Pharmaceuticals Inc
Disclosures for Mitchell R Smith, MD, PhD
Approximately how many new patients do you see per year with the following diseases?
Patterns of Care Survey of US-Based Practicing Oncologists (n = 100) and Clinical Investigators (n = 25), 2010.
CI (n = 25)
Median
PO (n = 100)
Median
Mantle-cell lymphoma (MCL) 15 2
Diffuse large B-cell lymphoma (DLBCL) 45 15
T-cell lymphoma (TCL) 10 2
Case History: Dr Smith
• An asymptomatic 82-year-old man presents with slowly progressive left cervical adenopathy
– Past medical history of hypertension, diabetes, high cholesterol and peripheral vascular disease
• Histopathology: Mantle cell lymphoma with t(11;14) on FISH
• CT scans: Adenopathy on both sides of diaphragm
• LDH normal
• No B symptoms
1) How would you initially treat this patient?
18%
11%
32%
13%
21%
5%
0%
0% 5% 10% 15% 20% 25% 30% 35%
R-Hyper-CVAD
Modified R-Hyper-CVAD (without methotrexate/Ara-C)
R-CHOP
R-CVP
R-bendamustine
Single-agent rituximab
Observation
Case History: Dr Smith (continued)
• Treated with single agent weekly-rituximab x 4 weeks
• Attained stable disease for approximately 10-months and then developed progressive adenopathy and mild anemia (Hb = 10.0 g/dL)
Case History: Dr Smith (continued)
• Patient treated with R-CVP x 6 and achieved PR
• CBC continues to show cytopenias
(Hb = 10.0 g/dL, Platelets = 110,000/mm3)
2) How would you manage the patient at this time?
8%
13%
3%
73%
3%
0%
0%
0%
0%
0% 10% 20% 30% 40% 50% 60% 70% 80%
Observation
Repeat single agent rituximab
R-bendamustine
Repeat R-CVP
R-CHOP
Modified R-Hyper-CVAD (without methotrexate/Ara-C)
Bortezomib
Lenalidomide
Cladribine
Case History: Dr Smith (continued)
• Patient treated with single-agent bortezomib on standard twice-weekly schedule
• Dramatic response with regression of nodes and normalization of blood counts
• Remained in near CR for two years
• CHOP rituximab – older patients who cannot tolerate more intensive therapy
• R-HyperCVAD/R-HDMtx + Ara-C (< 60-65?)• R-EPOCH • Modified R-HyperCVAD (part A) + rituximab maintenance
– in patients > 65 yrs• R-Bendamustine• Nordic regimen (R-Maxi-CHOP alt R-HiDAC auto SCT)• Cladribine + rituximab• Clinical trial• Observation for selected stage III-IV patients
*Select patients will undergo HDT/ASCT consolidation
Frontline Treatment Options for MCL*
Treatment Options for MCL in the Salvage Setting*
• Bendamustine ± rituximab• Bortezomib ± rituximab• Fludarabine based regimens ± rituximab• Lenalidomide ± rituximab• Temsirolimus• Thalidomide ± rituximab• PEPC (Prednisone, etoposide, procarbazine,
cyclophosphamide) ± rituximab
* Select patients will undergo HDT with allogeneic stem cell rescue (nonmyeloablative or myeloablative)
What is your usual initial treatment regimen for the following patients with newly diagnosed MCL?
60-Year-Old 75-Year-Old
CI
(n = 25)
PO
(n = 100)
CI
(n = 25)
PO
(n = 100)
R-CHOP Transplant 32% 19% 8% 5%
R-hyper-CVAD 20% 36% 4% 8%
Modified-R-hyper-CVAD 8% 27% 20% 9%
R-CHOP 8% 14% 20% 51%
Bendamustine + rituximab 8% 2% 44% 22%
Other 24% 2% 4% 4%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 100) and Clinical Investigators (n = 25), 2010.
Do you use R maintenance for patients with MCL?
22%
23%
54%
8%
32%
60%No
Yes, occasionally
Yes, usually
Patterns of Care Survey of US-Based Practicing Oncologists (n = 100) and Clinical Investigators (n = 25), 2010.
= Clinical Investigator
= Practicing Oncologist
When administering bortezomib for MCL, either alone or in combination with another agent (eg, rituximab) what schedule do you generally use?
11%
2%
35%
52%
4%
0%
12%
84%Biweekly
Weekly
Other
I do not administer bortezomib for MCL
Patterns of Care Survey of US-Based Practicing Oncologists (n = 98) and Clinical Investigators (n = 25), 2010.
= Clinical Investigator
= Practicing Oncologist
GOELAMS French Randomized Phase III Study of Maintenance Rituximab in Mantle Cell Lymphoma
www.clinicaltrials.gov, October 2010.
N = 199
Rituximab Maintenance500mg/m2 q-2 monthly x 3 Years
Primary Endpoint: Event Free Survival
Estimated Study Completion Date: September 2011
Observation
• Mantle Cell Lymphoma
• Age 18-65
• CD20-Positive
• Untreated Disease
Initial Treatment followed by High-Dose Chemotherapy
with Auto-transplant
Eligibility
CR or PR following Auto-Transplant
Ongoing Studies Incorporating Novel Agents Into First-Line Therapy of MCL
Study Phase N Treatment
BRIGHT III 296Bendamustine + rituximab
vsR-CVP or R-CHOP
NCT00114738 II 80EPOCH-R + bortezomib bortezomib
vsobservation
SWOG-S0601 II 60 CHOP-R + bortezomib bortezomib
ECOG-E1405 II 72Bortezomib + rituximab-CVAD
rituximab
GOELAMS-MANTEAU-2006-SA
II 39Bortezomib, rituximab, doxorubicin,
dexamethasone, chlorambucil
LENA-BERIT I/II 60 Lenalidomide, bendamustine, rituximab
www.clinicaltrials.gov, October 2010.
Copyright © 2010, Research To Practice, All rights reserved.
Bendamustine, Bortezomib and Rituximab in Patients with Relapsed/Refractory Indolent and Mantle Cell Non-Hodgkin Lymphoma (NHL): A Multicenter Phase II Clinical Trial
Friedberg JW et al.Proc ASH 2009;Abstract 924.
Efficacy of Bendamustine, Bortezomib and Rituximab in Relapsed Indolent and Mantle Cell Lymphoma
Overall Response
All Patients (n = 29) 79%
Relapsed or Refractory FL (n = 16) 85%
Relapsed or Refractory MCL (n = 7) 71%
Median of 4 prior treatment regimens
Friedberg JW et al. Proc ASH 2009;Abstract 924.
Studies of Bortezomib-Rituximab in Relapsed/Refractory NHL
Weekly Bortezomib in Non-Follicular and Mantle Cell Lymphomas (N = 49)1
Overall Response 1-Year Survival1-Year Progression-Free
Survival
53% 89% 45%
1Chiappella A et al. Proc EHA 2010;Abstract 271.2Agathocleous A et al. Br J Haemotol 2010;151(4):346-53.
Follicular and Mantle Cell Lymphomas (N = 42)2
Twice-Weekly Bortezomib (n = 21)
Weekly Bortezomib (n = 21)
Complete Response 14% 19%
Overall Response 67% 67%
Lenalidomide in Relapsed/Refractory MCL
Lenalidomide-Dexamethasone1 (N = 21)
Complete Response Overall Response
14% 52%
1Zaja F et al. Proc ASH 2009;Abstract 1713.2Wang L et al. Proc ASH 2009;Abstract 2719.
Lenalidomide-Rituximab2 (N = 45)
Complete Response Overall Response
Median Duration of Response
Median Progression-Free
Survival
31% 53% 18 months 14 months
— Margaret Deutsch, MDRaleigh, NC
Mantle cell is a real challenge, and my primary question is how aggressive to be with younger patients who have MCL? Are these patients really curable or is this just not a curable disease?
Does the panel really go the route of using hyper-CVAD in younger patients, and does that really end up producing long-term cures?
13%
3%
38%
46%
8%
8%
56%
28%
How would you compare the efficacy of R-hyper-CVAD versus R-CHOP followed by transplant in the front-line treatment of MCL?
R-hyper-CVAD is more efficacious than R-CHOP
followed by transplant
R-hyper-CVAD is about as efficacious as R-CHOP followed by transplant
R-hyper-CVAD is lessefficacious than R-CHOP
followed by transplant
I don’t know
Patterns of Care Survey of US-Based Practicing Oncologists (n = 100) and Clinical Investigators (n = 25), 2010.
= Clinical Investigator
= Practicing Oncologist
— Frank Rodriguez, MDFort Myers, FL
I have a 62-year-old patient with Stage I MCL, who underwent radiation therapy alone and did fantastically well. Now she is about a year out from diagnosis.
If she were to experience disease relapse, would the panel recommend chemotherapy or chemotherapy plus an autologous transplantation at this point?
Case History: Dr Horwitz
• A 45-year-old man with limited lymphadenopathy in the neck, mild fatigue
– Primary physician treats with antibiotics without response
• Needle biopsy: Questionable lymphoma, mostly T-cells
• Excisional biopsy: Apparent PTCL
• PET: Lymphadenopathy above and below the diaphragm
• Stage IV PTCL, NOS
– High LDH
– Good performance status
3) What treatment would you generally recommend?
4%
9%
36%
11%
39%
0% 10% 20% 30% 40% 50%
CHOP
HyperCVAD
CHOP + consolidation HDT/ASCR
Pralatrexate
Other
Case History: Dr Horwitz (continued)
• Patient treated with “accelerated” CHOP, ICE x 3 cycles and consolidation autotransplant
– In remission 8 months after therapy
4) If the patient relapsed one year after completing transplant, what treatment would you generally recommend?
5%
47%
2%
10%
10%
2%
19%
5%
0% 10% 20% 30% 40% 50%
DHAP
ESHAP
GDP
GemOx
ICE
MINE
Pralatrexate
Romidepsin
Classification of T-Cell Lymphomas
Mycosis FungoidesSezary SyndromePrimary cutaneous anaplastic large cell lymphoma
Other ExtranodalExtranodal NK/T cell lymphoma, nasal typeEnteropathy-type T cell lymphomaHepatosplenic T cell lymphomaSubcutaneous panniculitis-like T cell lymphoma
NodalAngioimmunoblastic T cell lymphomaPeripheral T cell lymphoma, unspecifiedAnaplastic large cell lymphoma
Neoplasm of Uncertain Lineage Blastic NK cell T-lymphomaPrecursor T-lymphoblastic leukemia/lymphoma
CTCL PTCL
Copyright © 2010, Research To Practice, All rights reserved.
International Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study: Pathology Findings and Clinical Outcomes
Vose J et al.J Clin Oncol 2008;26(25):4124-30.
Pathology Review of 1314 Cases of Peripheral T-Cell Lymphomas
PTCL, NOS
Angioimmunoblastic
Natural killer/T celllymphoma
Adult T-cellleukemia/lymphoma
Anaplastic large celllymphoma, ALK+
Anaplastic large celllymphoma, ALK-
Others
Vose J et al. J Clin Oncol 2008;26(25):4124-30.
Clinical Outcome by Histologic Subtype of Peripheral T-Cell Lymphomas
5-Year Overall Survival
5-Year Progression-Free
Survival
PTCL, NOS 32% 20%
Angioimmunoblastic 32% 18%
NK/T cell lymphoma (Nasal) 42% 29%
NK/T cell lymphoma (Extranasal) 9% 6%
Adult T-cell leukemia/lymphoma 14% 12%
Anaplastic large cell lymphoma ALK+ 70% 60%
Anaplastic large cell lymphoma ALK- 49% 36%
Vose J et al. J Clin Oncol 2008;26(25):4124-30.
Copyright © 2010, Research To Practice, All rights reserved.
Phase II Study of Denileukin Diftitox with CHOP Chemotherapy in Newly-Diagnosed PTCL: CONCEPT Trial
Foss FM et al.Proc ASCO 2010;Abstract 8045.
Phase II Study of Denileukin Diftitox + CHOP in Initial Treatment of PTCL (n = 49)
Complete Response
Overall Response
Median Response Duration Median PFS
2-Year Overall Survival
51% 65% 29 months 12 months 60%
The most frequent grade 3/4 AEs (>5%) were leukopenia (20%), thrombocytopenia (12%), and febrile neutropenia (12%).
Based on these results, a multi-center randomized trial comparing CHOP to denileukin diftitox + CHOP is being initiated.
Foss FM et al. Proc ASCO 2010;Abstract 8045.
Case History: Dr Horwitz
• A 71-year-old man with Stage II PTCL NOS with right cervical and right axillary nodes only
• Normal LDH
• Bone marrow negative
• Patient treated with CHOP x 6 and IFRT (Involved Field Radiation Therapy) and achieves CR
5) Would you advise high dose chemotherapy with stem cell transplant, while the patient is in 1st CR after treatment of stage II PTCL?
84%
16%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90%
Yes
No
Case History: Dr Horwitz (continued)
• Patient underwent active surveillance while in 1st CR
– 1-year later, disease recurs with diffuse lymphadenopathy without involvement of the bone marrow
6) How would you treat the patient at this time?
14%
3%
49%
3%
31%
0%
0%
0%
0% 10% 20% 30% 40% 50%
Salvage chemotherapy (like ICE, DHAP or MINE), with auto-
transplant if chemosensitive
Allogeneic transplantation
Pralatrexate
Romidepsin
Gemcitabine/oxaliplatin
Bortezomib
Lenalidomide
Denileukin diftitox
Case History: Dr Horwitz (continued)
• Patient receives pralatrexate and achieves a PR that is maintained for 10 months before progression
• Enrolls on a Phase II study of romidepsin and achieves a PR that is maintained for 8 months
– Restaging after cycle 8: Enlarging lymphadenopathy
What treatment do you generally recommend for relapsed/refractory PTCL?
15%
2%
36%
5%
32%
9%
0%
4%
16%
28%
48%
4%
Gemcitabine-based regimen
Romidepsin
Other*
* CHOP, fludarabine-based regimen, alemtuzumab, denileukin diftitoxPatterns of Care Survey of US-Based Practicing Oncologists (n = 81) and Clinical Investigators (n = 25), 2010.
Pralatrexate
I do not have any experience treating
relapsed PTCLSalvage regimens such
as ICE, ESHAP, DHAP
= Clinical Investigator
= Practicing Oncologist
Newly Approved Drugs in T-Cell Lymphomas
Pralatrexate• Chemotherapy• Folate analogue (Anti-metabolite)• FDA Indication: Relapsed or refractory Peripheral-T Cell Lymphoma• Recommended Dose: 30mg/m2 as IV push over 3-5 minutes, weekly
for six weeks in 7-week cycles
Romidepsin• Epigenetic Therapy• Histone Deacetylase (HDAC) Inhibitor• FDA Indication: Cutaneous T-Cell Lymphoma who have received at
least one prior systemic therapy• Recommended Dose: 14mg/m2 as IV infusion over 4 hrs; d 1, 8 and
15 of 28-day cycle
Copyright © 2010, Research To Practice, All rights reserved.
PROPEL: Results of the Pivotal, Multicenter, Phase II Study of Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)
O’Connor O et al.Proc ASCO 2009;Abstract 8561.
Efficacy and Safety of Single Agent Pralatrexate in Relapsed-Refractory PTCL
Complete Response (n = 109)
Partial Response (n = 109)
Overall Response(n = 109)
10% 17% 27%
Grade 3 / 4 Mucositis 21%
Grade 3 / 4 Thrombocytopenia 33%
O’Connor O et al. Proc ASCO 2009;Abstract 8561.
Median Prior Treatments = 3
Copyright © 2010, Research To Practice, All rights reserved.
Pralatrexate Activity in Patients with Relapsed-Refractory PTCL: Relationship between Response at Cycle 1 and Subsequent Survival
Coiffier B et al.Proc EHA 2010;Abstract 305.
Relationship of Response at Cycle 1 and Subsequent Survival: Pralatrexate PROPEL Trial
Per Independent Review (n = 90)
Per Investigators (n = 95)
RespondersNon-
Responders RespondersNon-
Responders
N 20 70 33 62
Median Survival
17.6 months 13.4 months 21.3 months 8.6 months
Hazard Ratio 0.69 0.46
p-value 0.32 0.01
Coiffier B et al. Proc EHA 2010;Abstract 305.
Copyright © 2010, Research To Practice, All rights reserved.
Romidepsin Experience in 317 Patients with T-Cell Lymphomas
Coiffier B et al.Proc EHA 2010;Abstract 572.
Activity of Romidepsin in Relapsed/Refractory PTCL and CTCL
PTCL CTCL
Overall Response 38% 34%
Complete Response 15% 6%
Median Duration of Response
10 months 13.7 months-15 months
Romidepsin resulted in clinically meaningful responses in CTCL and PTCL
Coiffier B et al. Proc EHA 2010;Abstract 572.
Case History: Dr Horwitz
• A 50-year-old man with extensive Stage IB CTCL who was treated at another institution with gemcitabine then bortezomib
• Presented with very extensive patch/ plaque disease and weepy sores
7) What treatment would you generally recommend?
38%
28%
21%
13%
0% 5% 10% 15% 20% 25% 30% 35% 40%
Some form of skin-directed therapy
Systemic therapy
Skin-directed therapy followed by
systemic therapy
I would refer to a tertiary center
Case History: Dr Horwitz (continued)
• Patient treated with total skin electrons
– Skin cleared
– Rapid relapse
• Patient treated with bexarotene but progressed
Case History: Dr Horwitz (continued)
• Patient treated with low-dose pralatrexate on protocol
– Doing well 9 months later
Treatment Options for CTCL
Skin-Directed Therapies
Topical SteroidsTopical nitrogen mustard, carmustineTopical retinoidsPhototherapy (PUVA, UVB)Localized RadiationTotal Skin Electron Beam Therapy
Systemic Therapies
RomidepsinVorinostatOral retinoids (e.g. bexarotene)InterferonsDenileukin diftitoxExtracorporeal photopheresisLiposomal doxorubicinGemcitabineEtoposideTemozolomideMethotrexateBortezomib
NCCN Clinical Practice Guidelines on Non-Hodgkin's Lymphomas, V.1.2010.
Copyright © 2010, Research To Practice, All rights reserved.
Final Results From a Multicenter, International, Pivotal Study of Romidepsin in Refractory Cutaneous T-Cell Lymphoma
Whittaker SJ et al.J Clin Oncol 2010;28(29):4485-91.
Efficacy of Romidepsin in Relapsed/Refractory CTCL (N = 96)
Overall Response Rate
Complete Response
Partial Response
Median Duration of Response
Time to Progression
34% 6% 28% 15 months 8 months
Whittaker SJ et al. J Clin Oncol 2010;28(29):4485-91.
Adverse Events All Grade Grade 3/4
Nausea 56% 2%
Asthenic conditions 44% 6%
Vomiting 26% 1%
Anorexia 20% 0%
Diarrhea 14% 1%
Copyright © 2010, Research To Practice, All rights reserved.
Pralatrexate Efficacy and Tolerability in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma (CTCL)
Horwitz M et al.Proc EHA 2010;Abstract 0300.
Efficacy of Pralatrexate in Relapsed/Refractory CTCL
Overall Response
(N = 47)Complete Response
Partial Response
Overall Response at Optimal Dose*
(N = 22)
40% 4% 36% 45%
*15 mg/m2 x 3/4 week
• 2 patients experienced Grade 3 mucositis• No patients experienced Grade 4 toxicity
Horwitz M et al. Proc EHA 2010;Abstract 0300.
Median Prior Systemic Therapies = 4 (Range 1-11)
Case History: Dr Smith
• A 52-year-old woman presents in 2002 with large mid-abdominal mass
• Diagnosed with Stage IIA diffuse large B-cell lymphoma (DLBCL)
• Patient received R-CHOP x 8 and achieves CRu
• No PET Scan is done
8) If PET scan is done, and shows focal residual activity, then what would be your next step?
12%
22%
56%
10%
0% 10% 20% 30% 40% 50% 60%
Observation
Involved field RT
2nd line chemotherapy followed by high-dose chemotherapy and
autologous transplant
Go directly to high-dose chemotherapy and autologous
transplant as her disease is chemo-responsive
Case History: Dr Smith (continued)
• Patient receives involved field radiation and remains in remission for two years
• Disease recurs above the diaphragm
• Patient treated with ICE followed by high-dose chemotherapy and autologous transplant
R-CHOP2 Cycles
R-ICE 4 Cycles
www.clinicaltrials.gov, October 2010.
Eligibility Criteria
Bulky Stage II or Stage III/IV DLBCL
Target Accrual: 99
ECOG-E3404: Response-Adapted Therapy for Aggressive NHL Based on Early PET Scanning
R-CHOP3 to 4
Cycles
PETSCAN
+
-
Do you use interim PET scanning in patients being treated for DLBCL?
After how many treatment cycles do you generally perform a PET scan?
CI (n = 14) Median PO (n = 84) Median
4 4
84%
56%
Yes
Patterns of Care Survey of US-Based Practicing Oncologists (n = 100) and Clinical Investigators (n = 25), 2010.
= Clinical Investigator
= Practicing Oncologist
— Frank Rodriguez, MDFort Myers, FL
I have a patient who presented with lymphadenopathy, was diagnosed with Stage III DLBCL, was treated with R-CHOP and did relatively well. However, he recurred in the same area 8 months later.
He wasn’t keen on using RICE salvage chemo as an inpatient (or as an outpatient) before transplant. He was hoping there was another regimen we could use on an outpatient basis.
What does the panel think about using GEM/OX-R as salvage chemotherapy prior to transplant? Are there any concerns about long-term toxicities that may preclude the patient from going to transplant, or should this regimen not be used outside of clinical trial in that setting?
— Neal Fischbach, MDFairfield, CT
I am curious about transplant for patients with primary, high-risk DLBCL.
There was a study from Sloan-Kettering where patients received risk-adapted therapy with three cycles of CHOP, then RICE. For patients who had high-risk disease at the outset or who did not respond well in the first three cycles of CHOP, they were getting transplanted at that point.
Does the panel think that we should be doing more of that in our young, healthy, high-risk patients?
— Richard Polkinghorn, MDBrunswick, ME
I have a 22-year-old patient who has DLBCL with Burkitt's-like features — Molecular testing was negative. Should we treat this patient with a Burkitt’s-like protocol, such as hyper-CVAD or R-CHOP, despite the negative molecular testing?
Also, does the panel believe that regimens like hyper-CVAD are more effective than R-CHOP in terms of overall survival?
top related