Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
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Patients with myeloma should be referred to
transplant:
A. Upon diagnosis
B. Upon progression
C. Upon diagnosis and
progression
D. Only if ≤ 65 years
old
E. After starting
treatment A. B. C. D. E.
0% 0% 0%0%0%
Current Challenges in Hematopoietic Stem Cell
Transplantation (HCT)
• Intensity/Toxicity of the conditioning regimen
• Donor availability
• Selection of suitable candidates for transplant
• Patient characteristics (age, functional status, co‐morbid conditions)
• Disease characteristics (chemoresistance, sensitivity to GVL)
• Timing of transplant (in the era of “novel” agents)
• Relapse after HCT (prevention, monitoring, treatment)
• Infections after HCT (prevention, monitoring, treatment)
• Graft vs Host Disease (prevention, monitoring, treatment)
• Access and financial burden of transplant
Conditioning Regimen Intensity
Gyurkocza1 B and Sandmaier BM. Blood: 124 (3): 344 - 353
Tumor killing +
Buying time for
GVL = Less
Relapse
Toxicity +
GVHD = Higher
Non‐relapse
mortality
GVL sensitivity
vs
Host fitness
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Timing of Transplant: Myeloma
Is autologous transplant still
needed for myeloma in the
era of novel agents?
Timing of transplant
Autologous Transplantation for Multiple Myeloma in the Era of New Drugs: A Phase III
Study of the Intergroupe Francophone Du Myelome (IFM/DFCI 2009 Trial) a391
• ASCT was found to improve PFS (stratified
p value for log‐rank test < 0.0002; HR=
1.5). 3‐year PFS 61% vs 48% in the RVD
arm.
• PFS benefit observed in the transplant
arm was uniform across age, cytogenetics
risk, and response after the 3 first cycles
of RVD (complete response or not).
• The 3‐year OS (88%) and similar between
the 2 study groups
• ASCT should remain standard of care in
myeloma
Attal M al. Abstract 391
Timing of transplant
A Salvage Autologous Stem Cell Transplant (ASCT2) Induces Superior Overall Survival
Following Bortezomib‐Containing Re‐Induction Therapy for Relapsed Multiple Myeloma
(MM): Results from the Myeloma X (Intensive) Trial a394
• PFS benefit observed in the ASCT arm; 67 m vs 31/39 m
• OS benefit at 4y: 69 vs 50%
• A second ASCT should be considered early in patients
with myeloma relapsing after first ASCT
Cook G al. Abstract 394
Relapsed myeloma after ASCT
Bortezomib‐Doxorubicin‐Dex (4 cycles)
Response (SD or better)
PBSC mobilization CY + G‐CSF
Randomization=174
ASCT CY weekly x 12 cycles
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Haploidentical transplants –post‐transplant
cyclophosphamide (PTCY)
• Markedly expands donor
availability especially for
minorities
• Shortens time to find a suitable
donor
• Major financial benefit – relevance
to underdeveloped countries
• Expansion of PTCY application
other HLA‐mismatched transplants
and other conditioning platforms
Luznik et al. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50.
Haploidentical transplants –post‐transplant
cyclophosphamide (PTCY)
• Two recent large CIBMTR analysis show similar outcomes to HLA
matched donors
• Uniformly lower incidence chronic GVHD with haplo‐HCT
• For AML, 3y OS was 45/46% haplo‐HCT vs 50/44% MUD (MA/RIC)
• For lymphomas, 3y OS was 61% vs. 62% MRD (with RIC)
• No difference in PFS or cumulative incidence of relapse with Haplo‐HCT
• No difference in TRM with Haplo‐HCT
Ciurea et al. Blood. 2015 Aug 20;126(8):1033-40
Ghosh et al Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors (2016) in press
Haploidentical transplants –PTCY
Survival after T‐Cell Replete Haploidentical Related Donor Transplant Using Post‐
Transplant Cyclophosphamide Compared with Matched Unrelated Donor (MUD)
Transplant for Lymphoid Malignancies a194
• Retrospective comparison of 917
adult pts with HL/NHL from CIBMTR
• cGVHD rates were 13% vs 51/33%
for MUD ‐/+ ATG (p<0.001)
• 3 y OS was 60%, 62% and 50%
• No difference in relapse rate, PFS,
or NRM
Mussetti A et al. Abstract 194
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Haploidentical transplants –PTCY‐ASH 2015 data (118 abstracts)
• China: RCT of 186 pts with Ph‐ ALL: 3 year OS 68% vs 64% (p=0.56) (Wang et
al a62)
• China: 514 pts with acute leukemias; 2y DFS >70% with extensive cGVHD 18%
(Zhao et al a3224)
• Mexico: 25 children/adolescents with hematological malignancies outpatient
transplants: 1‐year OS of 52% (Gonzalez‐Llano et al a4389)
• UK: 16 pediatric pts with hemoglobinopthies 15/16 achieved 90% donor
chimerism by T+180 (de la Fuente et al a4317)
• Italy: 31 pts with hematologic malignancies, RIC PBSC, 1 y OS of 55%, cGVHD
11% (Pastano et al a1924)
PTCY‐ Beyond Haploidentical transplants
Results of a Two‐Arm Phase II Clinical Trial Using Post‐Transplantation
Cyclophosphamide for Prevention of Graft‐Versus‐Host Disease in Haploidentical and
Mismatched Unrelated Donors Hematopoietic Stem‐Cell Transplantation a152
Gaballa S et al. Abstract 152
Haploidentical transplants –expanding donor availability
• Historically less than 50% of pts who needed an allogenic transplant
would have an HLA 8/8 fully matched donor
• Donor availability/eligibility remains a limitation in haploidentical donors
• Body weight limits umbilical blood (UCB) grafts as an option
• Report from MSKCC: 15% pts has no UCB graft options and 20% had no
haplo graft options (compromised donor availability was common in
minority patients) Ksouri at al. ASH 2015 a2027
• Potential for HLA‐mismatched URD with PTCY remains to be explored
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PTCY‐ HLA‐mismatched MUDs = Everyone has a donor!!
Nonmyeloablative (NMA), HLA‐Mismatched Unrelated Donor (mMUD) BMT with
High‐Dose Posttransplantation Cyclophosphamide (PTCy) Has Outcomes Similar
to Matched BMT a2002
Kasamon YL at al. Abstract 2002
Prevention of GVHD
Randomized Trial on GvHD Prophylaxis with or without Anti‐Human T‐
Lymphocyte Immunoglobulin ATG‐Fresenius (ATG‐F) in Allogeneic Hematopoietic
Cell Transplantation from Matched Unrelated Donors: Final Long‐Term Results
after 8.6 Years Median Follow‐up a853
• Incidence of extensive chronic GvHD after 8 years was 13.5% in the
ATG‐F group vs 51.8% in the control group (p<0.0001).
• The 8‐year rates: NRM 20.5% vs 34.0% (p=0.15), relapse 35.2% vs
29.9% (p=0.54), relapse mortality 30.8% vs 28.8% (p=0.90), DFS 44.3%
vs 36.1% (p=0.60), and OS 48.7% vs 36.8% (p=0.31)
• Support results from a Canadian RCT in 203 pts (13% vs 29% severe
cGVHD) (Walker et al. Lancet Oncol Dec 2015)
Finke J at al. Abstract 853
Prevention of Relapse after HCT
Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with
Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin
Lymphoma Patients at High Risk of Relapse a3172
Sweetenham at al. a3172
Moskowitz, at al. Lancet 2015. 385: 1853-62
PFS BV Placebo
2 y 65% 45%
3 y 61% 43%
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Too old for transplant ??‐ASH 2015
• CIBMTR analysis: Outcome of patients 65 years and older (n=699) with MDS
receiving Allo‐HCT similar to patients 55‐64 years of age (n=592) Attalah, at al.
a193
• Université de Montréal: 90 pts ≥ 60 y received auto‐HCT for lymphoma. Age
≥65 year was not associated with an increase TRM. Estimated 5 y OS is 62%
and PFS is 40%. TRM only 1% at 100 days and 2% at 1 y Lemieux, at al. a3171
• Germany: 187 pts with AML/MDS ≥ 60 y. OS at 3 y 35%. NRM and relapse at 1
y were 37% and 22%. Disease status and ECOG PS but not age were predictors
of poor outcomes Pohlen at al. a2025
• EBMT: 345 pts had allo‐HCT for MDS/sAML. 3y OS 33%. Only Karnofsy PS and
CMV positivity influenced survival Heidenreich, at al. a4390
“Surveillance imaging” doesn’t improve survival in lymphoma
after auto‐HCT‐ASH 2015
• Retrospective analysis of
194 of DLBCL patients after
auto‐HCT: radiographic vs
clinical relapse PFS/OS
218/643 vs 402/615 d
(p=NS) Epperla, at al. a4360
• Retrospective analysis of
148 of HL patients after
auto‐HCT: radiographic vs
clinical relapse PFS/OS
426/1270 vs 318/931 d
(p=NS) Kapke, at al. a3169
What is the upper age limit for marrow or
peripheral blood stem cell transplant?
A. 60
B. 70
C. 75
D. 90
E. Probably not 90, but I don’t
know!
A. B. C. D. E.
0% 0% 0%0%0%
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In 2016, how many % patients in the U.S. would
have an available donor for allogeneic stem cell
transplant?
A. 30%
B. 40%
C. 50%
D. 70%
E. >80%
A. B. C. D. E.
0% 0% 0%0%0%
Patients with myeloma should be referred to
transplant:
A. Upon diagnosis
B. Upon progression
C. Upon diagnosis and
progression
D. Only if ≤ 65 years
old
E. After starting
treatment A. B. C. D. E.
0% 0% 0%0%0%
HCT Take‐home messages‐ASH 2015
• Autologous stem cell transplantation should be considered in all patients with
myeloma; upfront and on progression
• Advanced age is no longer a contraindication for transplant
• Allogeneic transplant are becoming safer – less toxic regimens and better
GVHD prophylaxis (evolving role of HaploHCT and PTCY)
• More than 80% of patients now has a donor available for allogeneic transplant
• Transplant should be considered early in relapsed lymphoma and or high‐risk
lymphomas (myc or “double hit”, mantle, peripheral T‐cell lymphomas)
• Brentuximab maintenance should be considered in relapsed Hodgkin’s
lymphoma after autologous transplant