ASH Clinical News Focus on Myeloid Malignancies | Page 21

were neutropenia, thrombocytopenia, and anemia ( TABLE 2 ).
Nausea was the most common treatment-related AE (Reg 1A
= 62%; Reg 1B = 60%; Reg 2A = 40%; Reg 2C = 42%), and
neutropenia and thrombocytopenia were dose-limiting in
four patients.
TABLE 2. Most Common Grade 3/4 Adverse Events
Reg 1A Reg 1B
Reg 2A
Reg 2C
Neutropenia 23% 25% 15% 5%
Thrombocytopenia 23% 10% 20% 11%
Anemia 12% 0% 20% 16%
Reg = regimen
Again, the authors concluded that “HDM201 demonstrat-
ed a manageable safety profile and clinical activity in a heavily
pretreated population.” A planned dose-expansion study will
use Reg 1B because patients treated under this dosing schedule
had the lowest incidence of grade 3/4 thrombocytopenia while
achieving therapeutically relevant exposures.
There are limitations to both studies, including the small
patient populations and the high rates of thrombocytopenia.
In future studies, Dr. Hyman and researchers noted, HDM201
will be combined with eltrombopag to try to mitigate
thrombocytopenia.
References
1. Hyman D, Chatterjee M, de Vos F, et al. CT150 - Optimizing the therapeutic
index of HDM2 inhibition: Results from a dose- and regimen-finding Phase
I study of NVP-HDM201 in pts with TP53 wt advanced tumors. Presentation
#12356. Presented at the American Association for Cancer Research 2017
Annual Meeting, April 4, 2017; Washington, DC.
2. Stein E, Chromik J, DeAngelo D, et al. CT152 - Phase I dose- and regimen-
finding study of NVP-HDM201 in pts with advanced TP53 wt acute leukemias.
Presentation #12358. Presented at the American Association for Cancer
Research 2017 Annual Meeting, April 4, 2017; Washington, DC.
Nature of Prior Myeloid Neoplasm Influences
Outcome of Secondary AML
In an analysis of data from the European Society of Blood
and Marrow Transplantation (EBMT) registry, researchers
found that patients with secondary (transformed) acute
myeloid leukemia (AML) have varying outcomes dependent
on the myeloid neoplasm they had prior to progressing to
AML – myelodysplastic syndromes (MDS), myeloproliferative
neoplasms (MPN), or chronic myelomonocytic leukemia
(CMML) – and other risk factors. The investigators, led by
Nicolaus Kröger, MD, from the University Medical Center
Hamburg-Eppendorf in Hamburg, Germany, compared
3-year survival outcomes in patients with transformed AML
who received allogeneic hematopoietic cell transplantation
(alloHCT) between 2000 and 2014.
The study evaluated outcomes in 4,214 patients (39% female;
61% male) according to antecedent disease:
• MDS (n=3,541)
• CMML (n=251)
• MPN (n=422)
The median age at alloHCT was 58 years (range = 18-79 years),
and 59 percent of patients received a reduced-intensity (RIC)
conditioning regimen. The majority of patients received stem
cells from an unrelated donor (62%), and 50 percent were in
complete remission (CR) at the time of alloHCT.
Within the different primary disease subgroups, patients
with a primary diagnosis of MDS were more often in CR (53%)
at the time of transplant, compared with patients with under-
lying diagnoses of CMML (47%) or MPN (43%). RIC was also
more frequently used in MDS patients (65%) than in CMML
(64%) and MPN patients (58%; p values not provided).
After a median follow-up of 46.5 months, the estimated
3-year relapse-free survival (RFS) and overall survival (OS)
rates for the entire group were 36 percent (95% CI 34-38) and
40 percent (95% CI 33-42), respectively. The cumulative inci-
dences of relapse and non-relapse mortality were 37 percent
(95% CI 35-39) and 27 percent (95% CI 26-29), respectively.
In a univariate analysis, patients with MDS had a signifi-
cantly better 3-year OS and RFS than patients with CMML
(41% vs. 36% and 37% vs. 30%) and MPN (41% vs. 32% and
37% vs. 25%; p<0.001 for both). The survival benefit resulted
primarily from a lower incidence of relapse at 3 years (35% vs.
43% vs. 50%, p<0.001).
This study is limited by its retroactive registry design, and
molecular data were not routinely available from patients.
Reference
Kröger N, Eikema D, de Wreede L, et al. Different outcome of allogeneic stem
cell transplantation for transformed acute myeloid leukemia derived from MDS,
CMML or MPN. A retrospective study of the Chronic Malignancies Working
Party (CMWP) of EBMT. Oral abstract presented at the 43rd Annual Meeting of
the European Society for Blood and Marrow Transplantation, March 28, 2017;
Marseilles, France.
May 2017
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