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

434s Leukemia, Myelodysplasia, and Transplantation
6572 General Poster Session (Board #18G), Mon, 1:15 PM-5:15 PM
Treatment outcomes in patients older than age 60 with acute myeloid
leukemia (AML) in the nonclinical trial setting. Presenting Author: Steven
Duffy, SUNY Upstate Medical University, Syracuse, NY
Background: Optimal treatment of older adults with AML remains challenging.
While AML tends to be a disease of older adults, this population
experiences greater treatment-related toxicity and worse overall survival
than younger patients. Only fit older adults enter clinical trials and thus the
results may not apply to the entire population. Methods: We conducted a
retrospective analysis of patients � 60 years with AML (APL excluded)
diagnosed prior to 2008 with IRB approval. The association of clinical
factors (age, sex, comorbidities, prior chemotherapy), leukemia (prior
myelodysplastic syndrome or myeloproliferative neoplasm, cytogenetics,
WBC count), and therapy (induction chemotherapy, palliative chemotherapy,
and best supportive care) as they relate to overall survival was
evaluated using bivariate and multivariate regression analyses. Results: Of
87 patients (median age 73), 45% were male, 58% had high risk
cytogenetics, 38% had prior MDS/MPD, 92% were chemotherapy naive,
and 21% were in the high/very high Charlson risk class. The majority (67%)
received standard dose induction chemotherapy (IC), 9% received (palliative
intent) low-dose chemotherapy (LDC), and 24% received best supportive
care (BSC). The median overall survival (OS) of the entire cohort was 2.5
months. On bivariate analysis high WBC (�50,000 at presentation) was
negatively associated (1.0 vs 2.7 months p �0.01) with survival. OS for IC,
LDC, and BSC were 3.1, 2.8, and 0.7 months, respectively (p�0.001). On
multivariable analysis, IC conferred longer survival when compared to LDC
and BSC combined (OR 0.33 CI 0.2-0.6, p�0.001). High WBC was
associated with a decreased survival time (OR 2.96 CI 1.6-5.5, p�0.02).
Mortality during induction or consolidation chemotherapy was 38%. At
5-year follow-up, only 4 patients were alive. Conclusions: In a non-clinical
trial setting, OS of older adults with AML remains dismal. While IC offers a
chance of longer survival, mortality with IC is unacceptably high. Further
studies are required to identify and validate tools for risk stratification in
older adults with AML as well as to utilize therapies with an improved
toxicity profile.
6574 General Poster Session (Board #19A), Mon, 1:15 PM-5:15 PM
Evaluation of combination therapies with MOR00208, an Fc-enhanced
humanized CD19 antibody, in models of lymphoma. Presenting Author:
Mark Winderlich, MorphoSys AG, Martinsried/Planegg, Germany
Background: MOR00208 (formerly XmAb5574) is a Fc-engineered humanized
anti-CD19 antibody with superior cytotoxicity in a number of in vitro
and in vivo models of lymphoma and leukemia, currently being evaluated in
patients with relapsed/refractory CLL. Bendamustine (BEN), an alkylating
agent, fludarabine (FLU), a purine analogue, and the CD20 antibodies
rituximab (RTX) and ofatumumab (OFA) were evaluated for their ability to
enhance the cytotoxicity of MOR00208. Methods: Utilizing CD19/CD20�
MEC-1 CLL cells, cytotoxicity was assessed in vitro by flow cytometry.
MOR00208 was tested alone and in combination with BEN, FLU, RTX and
OFA using peripheral blood mononuclear cells as effector cells. Median
survival (MS) was evaluated in a murine model of disseminated lymphoma,
using i.v.-administered RAMOS cells (CD19�) and treatment with
MOR00208 alone and in combination with FLU. Combinatorial effects
were classified according to Chou-Talalay (Pharmacol Rev. 2006 Sep;58(3):
621-81). Results: MOR00208-mediated in vitro cytotoxicity was synergistically
enhanced by BEN, FLU and the CD20 antibodies irrespective of their
different modes of action (Combination Index � 1). In vivo, FLU alone at
doses up to the maximum tolerated dose (MTD) did not prolong MS,
whereas MOR00208 at 3 mg/kg increased MS by 26% compared to the
isotype control. Co-administration of MOR00208 with 125 mg/kg FLU
significantly enhanced MS by 65%. Despite its lack of single agent activity,
FLU thus significantly enhanced the cytotoxicity of MOR00208. Conclusions:
The cytotoxic in vitro activity of MOR00208 on CD19� B cells was
synergistically enhanced by all studied drugs irrespective of their effector
mechanisms. In vivo, the activity of MOR00208 in an aggressive lymphoma
model was potentiated in combination with FLU. These results provide a
mechanistic rationale for MOR00208 drug combinations which warrant
further evaluation in clinical trials.
6573 General Poster Session (Board #18H), Mon, 1:15 PM-5:15 PM
A simple but effective model to decrease early deaths in acute promyelocytic
leukemia (APL). Presenting Author: Anand P. Jillella, Department of
Medicine, Division of Hematology/Oncology, Georgia Health Sciences
University, Augusta, GA
Background: Recent reports suggest that approximately 30% of patients
with APL die during induction. This has been confirmed in large populationbased
studies in Sweden and the US. A recent analysis of SEER data from
13 population-based cancer registries with 1400 APL patients in the US
showed that 17% of all patients and 24% of patients greater than 55 years
of age die within one month of diagnosis. The most common causes of
death are bleeding, infection, differentiation syndrome and multi-organ
failure. Patients who survive induction have an excellent cure rate with few
late relapses. Hence, decreasing early deaths is a high priority both at
experienced as well as smaller centers with limited leukemia treatment
experience in this highly curable disease. Methods: At Georgia Health
Sciences University, between 7/2005 and 6/2009, 19 patients were
diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during
induction resulting in an unusually high mortality rate of 37%. All patients
who survived induction are still in remission at present. The high early
death rate prompted us to develop a simple, 2 page treatment algorithm
that focuses on quick diagnosis, prompt initiation of therapy, and proactive
and aggressive management of all the major causes of death during
induction. We also made our treatment protocol available to smaller
treatment centers and helped the treating oncologists manage the patient
during the first few days after diagnosis. Results: From 11/2010 to
12/2011, we treated 4 patients at GHSU and helped manage 4 patients at
2 outreach sites. The age range was 30 to 60; two patients were high-risk, 5
intermediate- and one low-risk. There were no deaths during induction and
all eight patients proceeded to consolidation treatment. Conclusions: While
we recognize that this is a small cohort, our own experience and a similar
approach pioneered by investigators in Brazil clearly shows this to be an
effective intervention to decrease early deaths in APL. We believe our
experience warrants large scale implementation of our protocol in an
attempt to reduce early APL mortality.
6575 General Poster Session (Board #19B), Mon, 1:15 PM-5:15 PM
Cancer testicular antigens as a prognostic markers of chronic lymphocytic
leukemia. Presenting Author: Julio C. Chavez, H. Lee Moffitt Cancer Center
& Research Institute, Tampa, FL
Background: CLL is the most common leukemia in adults and has a variable
course and prognosis. Clinical staging systems and the use of biomarkers
such as cytogenetics and the IGVH mutational status remain the gold
standard for stratification. Cancer testis antigens (CTAs) expression analyses
have shown prognostic impact in other hematological malignancies
such as acute leukemias and multiple myeloma. With the analysis of CTAs
we aim to discover additional molecular markers that can help us predict
the clinical course and outcome in CLL patients. Methods: We analyzed the
expression by RT-PCR of 39 known CTAs including members of the MAGE,
GAGE, MAD-CT and SSX CTAs families in a group of 59 CLL patients seen
at our institution. The Moffitt Cancer Center Total Cancer Care (TCC)
database was used to correlated these findings with relevant clinical and
molecular markers such as Rai stage, demographic data, initial WBC count,
IGVH mutational status, CD38 expression, cytogenetics by FISH analysis
and treatment outcomes. Overall survival (OS) and progression free survival
(PFS) were calculated using Kaplan Meier curves with a SPSS statistical
software Results: Deletion 13q was the most common gene abnormality in
35/59 (59.3%). 29/59 (49.1%) required at least one line of treatment.
MAGE family CTAs were present in 53/59 (83.9%), MAD-CT in 24/59
(40.7%), SSX in 14/59 (23.7%) and GAGE in 12/59(20.3%). 35/59
(59.3%) CLL patients expressed 2 or more MAGE family CTAs. No
differences were noted in the Rai staging, initial white blood cell count, B
symptoms, extranodal disease, presence of CD38, or unmutated IVGH. The
OS was not significantly different among all CTAs families with a tendency
towards a better OS those expressing the SSX family (p�0.63). Additionally,
CLL patients with single expression of MAD-CT1 (p�0.05) and
MAGE-B2 (p�0.038) antigens correlated with improved survival.
Conclusions: Patients with SSX family have a trend towards improved
survival. When analyzed by individual antigen, MAD-CT1 and MAGE-B2
expression was associated with improved survival. Further studies with a
larger number of patients are needed to assess the real value of the
expression of CTAs in CLL.
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