Annual Meeting Proceedings Part 1 - American Society of Clinical ...

6576 General Poster Session (Board #19C), Mon, 1:15 PM-5:15 PM
AML patients with IDH1 or IDH2 mutations treated with hypomethylating
agents: A case series. Presenting Author: Christopher Brent Benton,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations play a
significant role in acute myeloid leukemia (AML), yet optimal treatment for
AML patients with IDH mutations remains unclear. IDH mutations have
been associated with a globally hypermethylated genomic state, as the
result of increased levels of 2-HG, a regulator of histone methylation. We
sought to retrospectively determine responses of patients with IDHmutated
AML to treatment with hypomethylating agents. Methods: We
reviewed clinical data for AML patients treated at The University of Texas
M. D. Anderson Cancer Center from June 2001 to December 2011 whose
stored leukemia samples from bone marrow aspirateshad been tested
retrospectively for IDH1 and IDH2 mutations. We searched three databases
that contained records for 407 AML patients. We selected patients who had
been treated with the hypomethylating agents 5-azacitidine or decitabine,
alone or in conjunction with other therapeutics. We retrospectively reviewed
the patients’ medical records to obtain demographic, laboratory,
treatment, and clinical data. We evaluated response measured by remission
status, reduction in bone marrow blasts and peripheral blood blasts,
and time to relapse. Results: We identified 104 patients (25.6%) who had
either an IDH1 or IDH2 mutation, and of these, 8 patients had also been
treated with hypomethylating agents. A ninth AML patient, who is IDH2mutant,
is currently undergoing treatment with decitabine alone. Of these 9
patients, three had a durable complete remission without recovery of blood
counts (CRp), three had a partial response (PR), with or without blood
count recovery, and three had no response. All 9 patients did have an initial
decrease in the percentage of bone marrow blasts, peripheral blood blasts,
or both. Conclusions: This series of patients demonstrates the possibility
that AML patients with IDH1 or IDH2 mutations benefit from the use of
hypomethylating agents, and suggests it is worthwhile to prospectively
investigate treatment of patients with IDH-mutated AML using hypomethylating
agents.
6578 General Poster Session (Board #19E), Mon, 1:15 PM-5:15 PM
Analysis of outcomes of patients (pts) with blastic plasmacytoid dendritic
cell neoplasm (BPDCN). Presenting Author: Naveen Pemmaraju, University
of Texas M. D. Anderson Cancer Center, Houston, TX
Background: BPDCN, formerly known as CD4 � CD56 � hematodermic
tumor or blastic NK cell lymphoma, is a rare and aggressive hematologic
malignancy. Little is known about outcomes of pts with BPDCN. Methods:
We conducted a retrospective review of pts meeting following criteria:
pathological diagnosis of BPDCN confirmed by an experienced hematopathologist
and age � 18. Results: 13 pts, diagnosed October 1998-July
2011, were identified. Median (med) age: 62 years (range 20-86 years), 12
(92%) were male. Bone marrow (BM) involved in 9 (69%), skin 8 (62%),
lymph nodes 5 (38%), brain 1 and uterine/ovarian 1 pt. Immunophenotype
by flow cytometry: CD4� (11/11 pts), CD56� (10/11 pts), TCL-1� (4/4
pts). Karyotype (8 pts): del(12) (1pt), complex (2), and diploid (5). Med
CBC: WBC 5.8 x 109 /L (1.7-76.5), Hb 12.3 g/dL (8.3-17.0), platelet 107 x
109 /L (44-255). Med BM blasts: 22% (0-77). 10 pts received first-line
therapy with Hyper-CVAD alternating with high-dose methotrexate(MTX)
and cytarabine (HCVAD) (in 1 pt following one cycle of CHOP), CHOP (2),
oral MTX (1). Med follow-up time: 9 months (mo) (2-14 mo). Med number
chemotherapy regimens: 1 (1-5). Complete remission (CR) in 10 pts. Med
CR1: 19 mo (4-39 mo). Med overall survival (OS) 29 mo (1-44 mo). 9 pts
have died, unknown cause (3), multi-organ failure (6). 10 pts received
HCVAD as part of first line therapy: med OS: 29 mo (1-44 mo), med CR1:
21 mo (4-39 mo), 9/10 (90%) pts achieved CR1; 1 pt did not achieve CR1
(died, pneumonia, day 15). 9 pts (69%) had BM involvement (7 with other
organs involved besides BM). 4 (31%) pts had no BM involvement; all 4 of
these pts had skin involvement only. Med OS, med CR1 of pts with BM
involvement: 23 mo (1-44mo), 22 mo (4-39mo), respectively. Med OS,
med CR1 of skin only pts: 29 mo (2-31 mo), 7 mo (6-19 mo), respectively,
p�not significant. 4 pts received stem cell transplant (SCT) (2 allogeneic
,2 autologous). Med OS for pts receiving SCT (n�4) was 31 mo(8-31 mo)
versus med OS for non-SCT group (n�9) of 29 mo (1-44), p�not
significant. Conclusions: Despite intensive multi-agent chemotherapy and
SCT, response rates are low and survival is short. Better understanding of
the biologic basis of this disease and novel treatment approaches for
treatment of BPCDN are crucial.
Leukemia, Myelodysplasia, and Transplantation
435s
6577 General Poster Session (Board #19D), Mon, 1:15 PM-5:15 PM
Phase I dose escalation study of TG02 in patients with advanced hematologic
malignancies. Presenting Author: Gail J. Roboz, Weill Medical College
of Cornell University, New York, NY
Background: TG02 is a novel multikinase inhibitor with a unique spectrum
of activity, targeting both the cell cycle regulatory cyclin-dependent kinases
(CDKs) 1 and 2 and the transcriptional regulators CDKs 7 and 9. TG02 also
inhibits the emerging oncogenic MAPK ERK5 and the DNA damage
response mediator CDK5. TG02 kills primary blasts from a variety of
hematologic cancers and is curative in the MV4-11 model of FLT3-mutant
AML. Methods: This is a first-in-man,single arm, open label, phase I dose
escalation trial. The primary endpoints are dose-limiting toxicity (DLT),
maximally tolerated dose (MTD ) and recommended phase 2 dose (RP2D).
Patients (pts) � 18 years with advanced hematological malignancies or
newly diagnosed AML pts � 65 years unfit for intensive therapy were
enrolled onto daily (A) and intermittent (B, 5 days on 2 days off X 2 weeks)
schedules. Pts had acceptable organ function and ECOG PS 1-2. Definition
of DLT was G3-4 AST or ALT �7 days, G4 AST or ALT, G4 hyperbilirubinemia,
any other NCI CTC G3-4 events not due to underlying disease.
Dose levels on arm A were 10mg to 70mg and 15mg-150 mg on arm B.
Results: Forty-five pts have received at least one dose of study drug. Median
age was 66 years (range, 37-87) and 80% were ECOG 0-1. Disease types
enrolled included: AML (80%), high-risk MDS (22%), and CML-BC (3%).
The median number of previous regimens was 3 (range, 1-12). The MTD on
arm A was defined at 50 mg daily based on 2 DLTs at the 70mg dose level
(G4 hyperbilirubinemia, G4 fatigue). Enrollment to arm B has competed
dose levels 15 (N�3), 30 (N�3), 50 (N�3), 70 (N�3), 100mg (N�3),
and enrollment at 150mg is ongoing without DLT to date. Common drug
related adverse events were nausea (42%), vomiting (23%), fatigue (18%),
decreased appetite (15%), constipation and diarrhea (13% each). Preliminary
PK demonstrated dose proportional increases in exposure and a T1/2 ,
supporting once daily dosing. Conclusions: The MTD for TG02 has been
determined for the daily schedule at 50mg. Enrollment continues on the
intermittent schedule. Schedules of every other day and week on/week off
dosing will also be evaluated.
6579 General Poster Session (Board #19F), Mon, 1:15 PM-5:15 PM
Outcome of acute myeloid leukemia in patients with a history of autoimmune
disease. Presenting Author: Courtney Denton Dinardo, Hospital of
the University of Pennsylvania, Philadelphia, PA
Background: Increased risks of solid and lymphoid malignancies are
described in patients with autoimmune (AI) disease. The association
between AI disease, AI treatment (particularly anti-TNF therapy), and AML
is less established. Moreover, the pathologic characteristics of AML in this
population have not been evaluated. Here we describe our AML experience
in patients with prior AI disease. Methods: Patients with AML from 1992 to
2011 were identified from our database, and AI disorder was verified
through chart review. Patients were included if they had an AI disorder that
required systemic treatment, and diagnosed � 1 year prior to AML.
Patients were excluded if details including the year of AI diagnosis or
treatment(s) received were not documented. A total of 22 patients were
included for analysis. Results: Median age at AML diagnosis was 59 years
(range 32 – 78), 4 (18%) were men. 10 (48%) had received an anti-TNF
agent, for a median duration of 30 months (range 2 – 120). Median latency
from AI diagnosis to AML was 9.4 yrs. All FAB subtypes were represented
except M0 and M6, 9 (41%) had M4 or M5 disease. 10/21 patients (45%)
had normal cytogenetics, and 5 had favorable cytogenetics (2 with acute
promyelocytic leukemia (APML)). Standard induction was given to 19
patients, and APML-directed therapy for those with APML. One patient
received an autologous transplant in CR1, and 5 an allogeneic transplant (1
in CR1, 4 in CR2). 9 patients are alive in CR1. 13 relapsed, and 4 (31%)
are alive in CR2 or CR3 (3 following allogeneic transplant in later CR).
Median OS was 68.1 months. In univariate analysis, factors associated
with OS were cytogenetics, FAB subtype, and gender. Anti-TNF therapy
may be associated with poorer prognosis; this was not statistically significant.
Median OS was 14.1 months for poor, 68.1 months for intermediate,
and not reached for favorable risk cytogenetics. Conclusions: Median OS
was higher (� 5 years) than expected. Younger age and an increased
incidence of favorable risk AML may account for this finding: whether this
is a meaningful biologic association or stochastic event can only be verified
with larger studies. Our observations do not support a label of “secondary
leukemia” or therapy-related neoplasm in this population.
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