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

6568 General Poster Session (Board #18C), Mon, 1:15 PM-5:15 PM
Incidence of second and secondary malignancies in patients with CLL: A
single institution experience. Presenting Author: Samir Dalia, H. Lee
Moffitt Cancer Center & Research Institute, Tampa, FL
Background: Patients with chronic lymphocytic leukemia (CLL) have a
higher incidence of second malignancies than the general population with
one study showing the risk at 2.2 times the general popualtion. The
increased incidence is thought to be due to immunosupression which
results in decreased cell surveillance and proliferation of malignant cells.
Our study aims to present the rate of second malignancies by cancer type in
patients with CLL at our institution. Methods: The Moffitt Cancer Center
Total Cancer Care (TCC) database was used to identify patients who had a
diagnosis of CLL between January 1993-December 2009. Individual
charts were reviewed to confirm the diagnosis of CLL, collect demographic
data, and to assess for the presence of a second malignancy under an IRB
approved protocol. A second malignancy was defined as another malignancy
or transformation of CLL reported in the medical record. Second
malignancy data was placed in three categories; skin cancers, solid tumor
malignancy, and hematologic malignancy. Results: 546 CLL patients were
included in the study. Median age was 62.5 years. 84 (43%) were Stage 0
and 62 (32%) were Stage 1 RAI at diagnosis indicating earlier disease. 266
(49%) patients had a second or secondary malignancy. A total of 304
cancers were identified. 14% of patients had more than one malignancy.
Melanoma was identified in 44 (16.5%) patients and non-melanoma skin
cancer was identified in 54 (20%). Lung cancer was identified as the most
frequent solid tumor malignancy with 36 (13.5%) cases, followed by
prostate (35), breast (21), colorectal (15), and bladder (14). 10 patients
had a Richter’s transformation of their CLL. 26 patients developed either
myelodysplastic syndrome or acute myelogenous leukemia. Conclusions:
Second malignancies are frequent in CLL patients. Immunosupression,
increased UV light exposure, longer life expectancy in low risk CLL, and
tertiary cancer center referral bias are likely reasons for these increased
rates. Further research is needed to identify the precise mechanism which
cause patients with CLL to have higher rates of second malignancies and to
identify if there is an increased risk of a specific type of malignancy in
patients with CLL.
6570 General Poster Session (Board #18E), Mon, 1:15 PM-5:15 PM
Phase II study of AZD2171 for the treatment of patients with myelodysplastic
syndromes. Presenting Author: Shannon Eileen O’Mahar, University of
Wisconsin, Madison, WI
Background: Inhibition of vascular endothelial growth factor receptors
(VEGFR) can block growth and trigger apoptosis in neoplastic cells.
AZD2171 (cediranib) is a highly potent, orally bioavailable, VEGFR-1/2
inhibitor. We conducted a phase II study of the efficacy of AZD2171 for the
treatment of MDS. Methods: Adults with MDS (IPSS Int-2 or High) were
eligible if they exhibited adequate organ function and ECOG 0-2. The
primary endpoint was proportion of responses according to the IWG criteria
assessed at one and every 3 months. Prior investigation of cediranib at 45
mg daily in patients with acute leukemia demonstrated toxicity concerns
and therefore, the starting dose of this study was lowered to 30 mg daily.
Results: A total of 16 pts with MDS (median age 73 years) were enrolled at a
30 mg starting dose, and all were evaluable. Median baseline marrow blasts
were 12.0 % (range 2-18); 3 pts (18.8 %) had low, 6 (37.5 %)
intermediate, and 7 (43.8 %) had high risk cytogenetics. Prior therapy
included azacitidine (n�7), decitabine (n�2), cytarabine (n�2), erythropoietin-stimulating
agents (ESAs) (n�2), lenalidomide (n�1), or none
(n�6). Patients were treated for a median of two 28-day cycles (range 1 to
11). There were no confirmed responses. Patients with baseline blasts �
5% showed no significant reduction in the blast count at 4 and 12 weeks.
Median OS was 4.7 mo (95% CI: 2.6 – 11.6). Median TTP was 3.8 mo
(95% CI: 1.7 – 10.8). Grade 4 hematological adverse events at least
possibly related to cediranib were neutropenia (n�2) and thrombocytopenia
(n�4). Grade 3 hematological adverse events at least possibly related to
study treatment included: neutropenia (n�3), thrombocytopenia (n�2),
and anemia (n�2). Grade 3 non-hematological adverse events included
fatigue (n�4), dyspnea (n�3), dehydration (n�2), diarrhea (n�2), nausea
(n�2), asthenia (n�1), and hypertension (n�1). Hypertension and proteinuria
was uncommon with the 30 mg/day dose. Conclusions: With no
confirmed response from 16 patients, cediranib was determined to be
ineffective at a dose of 30 mg daily in our patient population. Supported by
NCI N01-CM62205, NCI P30-CA014520 and the UW Carbone Comprehensive
Cancer Center.
Leukemia, Myelodysplasia, and Transplantation
433s
6569 General Poster Session (Board #18D), Mon, 1:15 PM-5:15 PM
Induction chemotherapy with high-dose cytarabine and mitoxantrone in
elderly acute myeloid leukemia (AML) patients. Presenting Author: Muthalagu
Ramanathan, UMass Memorial Medical Center and UMass Medical
School, Worcester, MA
Background: Induction chemotherapy is often not used in elderly patients
with AML due to poor prognosis and inferior outcomes. We present here our
experience in treating 20 patients age�70yrs with an induction regimen
consisting of high dose cytarabine and mitoxantrone (HiDAC/MITO).
Methods: We analyzed all patients age � 70 years who underwent induction
with HiDAC/MITO at our institution from January 2009 to December 2011.
20 patients received HiDAC at 3 g/m2 daily on days 1-5 and mitoxantrone
80mg/m2* once on day 2(*one patient received 60mg/m2). The end points
analyzed were complete remission (CR) and induction mortality at day 30,
overall survival and progression free survival. Results: Median age was 75
years (70-83). 11 (55%) patients were male and 9 (45%) patients were
female. Median duration of follow up of 10 (50%) patients who are still
alive at the time of this analysis is 439 days (38-1095). High risk
cytogenetics was noted in 11 (55%) patients including two patients with
FLT3 mutated cytogenetics. Intermediate risk cytogenetics was noted in 9
(45%) patients including 2 patients with NPM1 mutated FLT 3 WT AML.
12 (60%) patients had secondary AML. The age unadjusted charlson
comorbidity index (CCI) was 3 (2-9). 15 (75%) patients attained CR and 3
(15%) patients attained a CR with incomplete platelet recovery (CRp). CR
�CRp rate was 90%. Two (10%) patients were refractory to induction and
5 (25%) patients relapsed at a later time point after induction. Median
duration of hospital stay was 28 days (22-60). Median time to ANC �1K
was 23.5 days (18-29), excluding 2 patients who had refractory disease.
Median time to platelet recovery �100K was 25 days (20-44), excluding 2
patients with refractory disease and 3 patients with CRp. Regimen related
toxicity included cardiac toxicity in 4 patients and bacteremia in 11
patients. Five (25%) patients were consolidated with stem cell transplant.
Median overall survival (OS) was 151 days (38-1095) and progression free
survival (PFS) was 131 days (38-1049). Conclusions: HiDAC/MITO induction
is well tolerated by elderly patients with AML and demonstrates an
overall response (CR�CRp) rate of 90% coupled with no induction deaths.
6571 General Poster Session (Board #18F), Mon, 1:15 PM-5:15 PM
Overall and cancer-specific survival of breast, colon, and lung cancer in
patients with and without chronic lymphocytic leukemia: A SEER populationbased
study of over 1 million patients. Presenting Author: Benjamin M.
Solomon, Mayo Clinic, Rochester, MN
Background: Chronic lymphocytic leukemia (CLL) is associated with an
increased risk of developing second cancers. However, it is unknown
whether CLL alters the natural history of these cancers once they occur.
Methods: All patients with breast (n�583,838), colon (n�412,932),
prostate (n�632,922), lung (n�489,290), kidney (n�95,902), pancreas
(n�82,121) and ovarian (n�61,958) cancer reported to the Surveillance,
Epidemiology, and End Results (SEER) Program from 1990 to 2007 were
identified. Overall survival (OS; death due to any cause) and cancer-specific
survival (death due to cancer site of interest) were examined, comparing
patients with or without pre-existing CLL. Age- and sex-adjusted hazard
ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL
was inferior for patients with breast (HR�1.61; p�0.001), colon
(HR�1.65; p�0.001), kidney (HR�1.41; p�0.001), prostate (HR�1.75;
p�0.001), and lung (HR�1.22; p�0.001) cancer after adjusting for age
and sex. After excluding CLL-related deaths, OS remained shorter among
patients with breast (p�0.001), colon (p�0.001), kidney (p�0.03),
prostate (p�0.001), and lung (p�0.001) cancer. Cancer-specific survival
was inferior for patients with breast (HR�1.29; p�0.03), colon (HR�1.75;
p�0.001), and lung cancer (HR�1.17; p�0.001) who had pre-existing
CLL after adjusting for age and sex. Conclusions: Several common cancers,
including breast, colon, and lung, have inferior overall and cancer-specific
survival when there is coexistent CLL.
HRs for OS by cancer type.
OS, including CLL deaths OS, excluding CLL deaths
Cancer HR 95% C.I. p value HR 95% C.I. p value
Breast 1.61 1.44-1.80 �0.001 1.38 1.21-1.57 �0.001
Colon 1.65 1.52-1.78 �0.001 1.59 1.46-1.74 �0.001
Kidney 1.41 1.19-1.68 �0.001 1.25 1.02-1.52 0.03
Lung 1.22 1.15-1.29 �0.001 1.20 1.12-1.28 �0.001
Ovary 1.13 0.86-1.49 0.38 0.98 0.73-1.33 0.91
Pancreas 1.00 0.84-1.19 1.00 0.98 0.82-1.17 0.83
Prostate 1.75 1.62-1.90 �0.001 1.35 1.22-1.50 �0.001
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