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W E I L L . C O R N E L L . E D U
Should All Eligible Patients with Mantle Cell Lymphoma Be
Transplanted?
Answer: No
Peter Martin, M.D.
The Charles, Lillian and Betty Neuwirth Clinical Scholar in Oncology
Assistant Professor of Medicine
W E I L L . C O R N E L L . E D U
Let’s define “eligible”
5%
6%
89%
Real-World Upfront Management
RadiationNo therapySystemic therapy
N=1066
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Let’s define “eligible”
5%6%
89%
Proportion of Patients Receiving Systemic Therapy
RadiationNo therapySystemic therapy
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Let’s define “eligible”
62%
38%
Age of Patients Receiving Systemic Therapy
>65 years<65 years
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Let’s define “eligible”
36%
64%
Treatment of <65 years
OtherMCL2
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Let’s define “eligible”
76%
24%
Proportion of Patients Undergoing Autologous Stem Cell Transplantation
Not transplantTransplant
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Should 24% of All Patients with Mantle Cell Lymphoma Be Transplanted?
Answer: No
Peter Martin, M.D.
The Charles, Lillian and Betty Neuwirth Clinical Scholar in Oncology
Assistant Professor of Medicine
W E I L L . C O R N E L L . E D U
Overall Survival Is Better in Real-World Patients That Undergo ASCT
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
But Overall Survival Is Even Better in Patients That Don’t Undergo Any Treatment
Abrahamsson A et al. Blood 2014;124:1288-1295
W E I L L . C O R N E L L . E D U
Interpretation: Observational data is not particularly helpful here.
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Provides Durable Remissions!!
Damon L E et al. JCO 2009;27:6101-6108
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Provides Durable Remissions
Damon L E et al. JCO 2009;27:6101-6108British Journal of Haematology Volume 158, Issue 3, pages 355-362
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Provides Durable Remissions
Damon L E et al. JCO 2009;27:6101-6108British Journal of Haematology Volume 158, Issue 3, pages 355-362
Fenske T S et al. JCO 2014;32:273-281
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Provides Durable Remissions
Damon L E et al. JCO 2009;27:6101-6108British Journal of Haematology Volume 158, Issue 3, pages 355-362
Fenske T S et al. JCO 2014;32:273-281Dreyling. Blood 2005; 105:2677-2684
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Does Not Result in Cure
Damon L E et al. JCO 2009;27:6101-6108British Journal of Haematology Volume 158, Issue 3, pages 355-362
Fenske T S et al. JCO 2014;32:273-281Dreyling. Blood 2005; 105:2677-2684
W E I L L . C O R N E L L . E D U
Autologous Stem Cell Transplantation Is Associated with a
5-10% Mortality Rate
Study Treatment-Related Mortality
Dreyling 8% (Infection)
MCL2 NRM=7.5% @ 7.4 years
MCL3 NRM=6.9% @ 4.4
CALGB 59909 67 of 79 patients received ASCTNRM = 2
CIBMTR 1-year NRM = 3%
Dreyling. Blood 2005; 105:2677-2684British Journal of Haematology Volume 158, Issue 3, pages 355-362
Damon L E et al. JCO 2009;27:6101-6108Fenske T S et al. JCO 2014;32:273-281
W E I L L . C O R N E L L . E D U
Hoster E et al. JCO 2014;32:1338-1346
European MCL Younger: MIPI Predicts Outcome Post-Transplant
W E I L L . C O R N E L L . E D U
MCL2: MIPI Predicts Outcome Post-Transplant
British Journal of HaematologyVolume 158, Issue 3, pages 355-362, 29 MAY 2012
W E I L L . C O R N E L L . E D U
Response to Induction Pre-Transplant Predicts Outcome Post-Transplant
Kolstad A et al. Blood 2014;123:2953-2959
W E I L L . C O R N E L L . E D U
MCL3: Pre-Transplant PET Predicts Outcome Post-ASCT
Kolstad A et al. Blood 2014;123:2953-2959
W E I L L . C O R N E L L . E D U
Clinical Lymphoma Myeloma and Leukemia, Volume 14, Issue 2, 2014, 114 - 121
U Minn: Pre-Transplant PET Predicts Outcome Post-ASCT
W E I L L . C O R N E L L . E D U
European MCL Younger Trial: Pre-Transplant MRD Status Predicts Outcome Post-ASCT
Williams M E Hematology 2013;2013:568-574
W E I L L . C O R N E L L . E D U
MCL3: Pre-Transplant MRD Status Predicts Outcome Post-ASCT
Kolstad A et al. Blood 2014;123:2953-2959
W E I L L . C O R N E L L . E D U
Liu H et al. Haematologica 2012;97:579-585
CALGB59909: Pre-Transplant MRD Status Predicts Outcome Post-ASCT
W E I L L . C O R N E L L . E D U
Should 12% of All Patients with Low-Risk, PET-Negative, MRD-Negative
Mantle Cell Lymphoma Be Transplanted?
Answer: No
Peter Martin, M.D.
The Charles, Lillian and Betty Neuwirth Clinical Scholar in Oncology
Assistant Professor of Medicine
W E I L L . C O R N E L L . E D U
How Does ASCT Prolong Survival?
• Eliminate sub-clones before they accumulate new mutations that confer resistance to subsequent treatment
W E I L L . C O R N E L L . E D U
C h e m o t h e r a p y w o r k s b y i n d u c i n g d s D N A d a m a g e
W E I L L . C O R N E L L . E D U
Frequent Somatic Mutations in The DNA Damage Response Pathway
Beà S et al. PNAS 2013;110:18250-18255
W E I L L . C O R N E L L . E D U
Nordic MCL2/3: TP53 add prognostic information to MIPI
British Journal of HaematologyVolume 166, Issue 1, pages 98-108, 29 MAR 2014 DOI: 10.1111/bjh.12854
W E I L L . C O R N E L L . E D U
Complex karyotype in mantle cel l lymphoma is a prognostic factor
Genes, Chromosomes and CancerVolume 53, Issue 1, pages 106-116, 29 OCT 2013 DOI: 10.1002/gcc.22123
W E I L L . C O R N E L L . E D U
Interpretation:~50% of MCL cases may be chemoresistant at diagnosis
W E I L L . C O R N E L L . E D U
Should X% of All Patients with Low-Risk, PET-Negative, MRD-Negative,
TP53W T , ATMW T Mantle Cell Lymphoma Be Transplanted?
Answer: No
Peter Martin, M.D.
The Charles, Lillian and Betty Neuwirth Clinical Scholar in Oncology
Assistant Professor of Medicine
W E I L L . C O R N E L L . E D U
Can Chemotherapy Make Cancer Worse?
Levine et al. Nature Medicine 2014;20(4)
W E I L L . C O R N E L L . E D U
Chemotherapy Increases Clonal Heterogeneity in CLL
Landau, D.A. et al. Cell 152, 714–726 (2013).
W E I L L . C O R N E L L . E D U
Should X% of All Patients with Low-Risk, PET-Negative, MRD-Negative,
TP53W T , ATMW T Mantle Cell Lymphoma Be Transplanted?
Answer: NoPeter Martin, M.D.
The Charles, Lillian and Betty Neuwirth Clinical Scholar in Oncology
Assistant Professor of Medicine
W E I L L . C O R N E L L . E D U
Conclusions• The minority of patients with MCL are eligible to receive
aggressive transplant.– Is this question even relevant to real-world practice?
• Conventional chemotherapy does not cure MCL, regardless of the dose. But it dose induce real toxicity.– Do the ends justify the means?
• Aggressive approaches appear to be most active in patients with the best prognosis.– There is a clear selection bias in data.
W E I L L . C O R N E L L . E D U
Conclusions• MCL is inherently chemoresistant
– More chemotherapy doesn’t make it better
• Chemotherapy can induce clonal heterogeneity– May be worse in the long run
• Aggressive therapies should be undertaken in the context of a clinical trial.
• Honest and open discussions with patients should guide management decisions.