ASH Clinical News Focus on Myeloid Malignancies | Page 25

treatment arms, though there was a slightly higher rate of AEs
in the vorinostat-treated group, which Dr. Garcia-Manero noted
“was to be expected,” given its known toxicities.
“The good news is that the response rates and the survival
rates [in the IA and IA+V arms] were acceptable, but we were not
able to demonstrate superiority of these approaches to 7+3,” he
concluded. “For now, based on this study, a 7+3 approach is still
the standard of care for patients with AML.”
Future studies, he added, should compare the 7+3 regimen
with combination treatments that include nucleoside analogues,
monoclonal antibodies, or targeted agents.
Earlier AlloHCT Should Be a New Standard
As a secondary aim of the SWOG S1203 trial, researchers sought
to transplant all cytogenetically determined high-risk patients
during first CR (CR1), to determine if proceeding to transplant
before a relapse could improve patients’ survival. 2
“Although prior studies suggest a better outcome in high-risk
AML patients in CR1 who undergo alloHCT, compared with con-
solidation chemotherapy, only 40 percent of such patients actually
proceed to transplant,” lead author John M. Pagel, MD, PhD, of
the Swedish Medical Center in Seattle, Washington, said during
his presentation of the results. “This study showed we can get
significantly more high-risk AML patients to a stem cell transplant
before their cancer recurs by simply working hard to identify an
appropriate donor and proceeding to transplantation as soon as
possible. … This process may establish a new standard of care.”
Using the same SWOG S1203 population analyzed in the study
by Dr. Garcia-Manero and colleagues, Dr. Pagel and researchers
conducted expedited human leukocyte antigen-typing in the 159
patients with high-risk cytogenetics (22% of the total population).
Patients were also encouraged to be referred for consultation with a
transplant team with the goal of conducting an alloHCT during CR1.
Overall, 107 high-risk patients achieved CR/CR with incom-
plete blood count recovery (CRi) (67%). AlloHCT was performed
in 43 percent of the entire SWOG S1203 population, and 68 (64%)
of the high-risk patients (significantly higher than the historical
rate of 40%; p<0.001). Of the high-risk population:
• 25 patients had a matched related donor (37%)
• 31 had a matched unrelated donor (45%)
• 3 had a mismatched related donor (4%)
• 8 had a mismatched unrelated donor (12%)
• 1 received an umbilical cord blood transplant (1%)
Of the 66 high-risk patients transplanted in CR/CRi with
detailed data available, the median time to alloHCT from CR1
was 76 days (range = 20-365 days). Fifty-seven patients (86%)
received a myeloablative regimen and nine (14%) received
reduced-intensity conditioning. The reasons for not proceeding
to alloHCT were varied: Relapse (n=6), death (n=6), physician
decision (n=3), patient decision (n=3), co-morbidities (n=1),
no insurance (n=1), no donor (n=1), other (n=10), or unknown
(n=8).
AlloHCT during CR1 appeared to increase the median OS by
6 months, compared with high-risk patients who did not receive
alloHCT: 18 (range = 3-33 months) versus. 12 months (range =
3-33 months).
The 2-year RFS estimate in the entire high-risk cohort is 32
percent, which the authors found was significantly higher than the
22 percent historical rate (p=0.05). Median RFS in the high-risk
CR1 cohort (n=107) was 10 months (range = 1-32 months), and
1-year estimates of RFS and OS were similar regardless of type of
donor (matched related = 40% and 56%, respectively; matched
unrelated = 52% and 56%, respectively).
“Cytogenetic testing with an organized effort to identify
a suitable donor led to a high CR1 transplant rate, which in
turn led to a significant improvement in RFS over historical
controls,” the authors concluded. “Better outcomes in poor
prognosis AML patients may be achieved simply by rapidly
finding unrelated donors and performing alloHCT in CR1 as
soon as possible.”
References
1. Garcia-Manero G, Othus M, Pagel JM, et al. SWOG S1203: a randomized p hase III study
of standard cytarabine plus daunorubicin (7+3) therapy versus idarubicin with high dose
cytarabine (IA) with or without vorinostat (IA+V) in younger patients with previously
untreated acute myeloid leukemia (AML). Abstract #901. Presented at the 2016 ASH
Annual Meeting, December 5, 2016; San Diego, California.
2. Pagel JM, Othus M, Garcia-Manero G, et al. Feasibility of allogeneic hematopoietic cell
transplantation among high-risk AML patients in first complete remission: results
of the transplant objective from the SWOG (S1203) randomized phase III study of
induction therapy using standard 7+3 therapy or idarubicin with high-dose cytarabine
(IA) versus IA plus vorinostat. Abstract #1166. Presented at the 2016 ASH Annual
Meeting, December 5, 2016; San Diego, California.
More Mutations, More
Problems? Assessing
Mutation Burden and
Response to HMAs in MDS
Previous research has suggested that the presence of a TET2
mutation can predict which patients with myelodysplastic
syndromes (MDS) are more likely to have a favorable
response to hypomethylating agents (HMA; the standard
of care for higher-risk MDS). However, a study presented by
Guillermo Montalban-Bravo, MD, from the Department of
Leukemia at the University of Texas MD Anderson Cancer
Center in Houston, at the 2016 ASH Annual Meeting did not
find that the presence of a TET2 mutation was significantly
associated with an increased response rate to HMA.
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May 2017
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