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

6608 General Poster Session (Board #23C), Mon, 1:15 PM-5:15 PM
Impact of immunoglobulin heavy chain variable region mutational status on
the outcome of patients with chronic lymphocytic leukemia harboring
isolated 13q deletion. Presenting Author: Gelenis C. Domingo, H. Lee
Moffitt Cancer Canter & Research Institute, Tampa, FL
Background: Several prognostic factors can predict the course of chronic
lymphocytic leukemia (CLL). Among them, the IGVH mutational status and
the presence of cytogenetic abnormalities are the strongest predictors of
outcome. Mutated IGVH and deletion 13q independently confer a survival
advantage. CLL patients with mutated IGVH in combination with deletion
13q have a better prognosis when compared to their unmutated IGVH
counterparts. However, there is limited data on the outcome of patients
harboring favorable deletion 13q and the unfavorable unmutated IGVH.
This study aimed at identifying patients with these two indicators in order
to obtain important prognostic information. Methods: We used the Moffitt
Cancer Center Total Cancer Care (TCC) database to find patients with a
diagnosis of CLL between January 1993 and December 2009. Individual
charts were reviewed for demographic data and CLL cytogenetics, including
IGVH mutation status and presence of deletion 13q. We analyzed the
impact of having deletion 13q in combination with an unmutated IGVH on
the overall survival (OS) for this subset of CLL patients using Kaplan Meier
curves with SPSS statistical software. Results: 546 patients were identified
during the aforementioned time period with a diagnosis of CLL. Median age
was 62.5 years. 144 (26.4%) of these patients had IGVH and cytogenetic
analysis available. 53 patients had 13q deletion as their sole genetic
abnormality. Patients with unmutated IGVH and positive for deletion 13q
were 19/53 (35.8%). Patients with mutated IGVH and positive for deletion
13q were 34/53 (64.2%). Patients with mutated IGVH and positive for
deletion 13q had an OS of 17 years. While patients with unmutated IGVH
and positive deletion 13q had a lower median OS of 12 years (91.2% vs
78.9%, p�0.05). Hazard ratio for patients with IGVH mutated and positive
deletion 13q was 0.4, p�0.05. Conclusions: Mutated IGVH appears to be
associated with improved OS in patients with isolated 13q deletion when
compared to patients with unmutated IGVH and isolated 13q deletion.
Further research is needed to assess these mutations in relation to other
cytogenetic abnormalities in CLL.
6610 General Poster Session (Board #23E), Mon, 1:15 PM-5:15 PM
Assessment of age as its own risk factor in AML. Presenting Author: Thomas
Buchner, University of Muenster, Muenster, Germany
Background: Patients’ age is an important issue in treatment decisions for
AML, while its role in this disease remains poorly explained. Methods: In the
AMLCG 1999 trial 1223 patients (pts) were 16-59y and 1470 pts were
60-85y of age. Their treatment was randomized between TAD-HAM vs
HAM-HAM induction (TAD, standard dose thioguanine, cytarabine, daunorubicin
60mg/m² x 3; HAM, high-dose cytarabine 3g/m² x 6, mitoxantrone
10mg/m² x 3), TAD consolidation and monthly maintenance vs autologous
SCT, any chemotherapy � vs - G-CSF priming. All randomization was done
upfront. Pts of �60y received routine double induction and full dose HAM
while pts of 60�y preferentially received only one course induction and
HAM at 1g instead of 3g cytarabine /m² x6.Results: With little differences
according randomizations, pts �60y and 60�y achieved a complete
remission rate (CR) of 70.2% and 53.5% (p�.001), overall survival (OS) at
5y of 41.3% and 12.9% (p�.001) and a relapse rate (RR) of 49.0 and
72.0% (p�.001). We also focussed on pts around 60y of age and
compared the 172 pts of 57-59y with the 261 pts of 60-62y excluding pts
undergoing allogeneic stem cell transplantation. According to their similar
age the two groups showed similar baseline characteristics. In contrast and
due to the cut-off point for age adaption at 60y they differed considerably in
treatment. Expressed by the cumulative dosage of cytarabine, the difference
between the two groups was by factor 2.9. This difference, however,
did not translate into a different outcome being 62% vs 60% CR, 28% vs
21% 5y OS (p�0.25), and 73% vs 73% RR at 5y. A multivariable analysis
in all pts between 16 and 85y of age identified cytogenetik/ molecular risk
and age as a continuous variable, to be risk factors predicting CR, OS, as
well as RR. In pts of 16-60y those below and above the median age of 47y
differed in their CR rate by 75% vs 66% (p�.001), their OS by 49% vs
35% (p�.001) and in their RR by 45% vs 53% (p�.007). In pts of 60-85y
those below and above the median age of 67y differed in their CR rate by
57% vs 51% (p�.023), and their OS by 16% vs 11% (p�.001), while their
RR was similarly 71%. Conclusions: The outcome in pts with AML is
substantially determined by patients’ age as its own risk factor, and not by
treatment intensity.
Leukemia, Myelodysplasia, and Transplantation
443s
6609 General Poster Session (Board #23D), Mon, 1:15 PM-5:15 PM
A new paradigm in CLL: Minimizing toxicity by using the minimum effective
dose (MED) of lenalidomide for older patients with CLL. Presenting Author:
Nicole Lamanna, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: While CIT has proven active for younger patients with CLL;
studies from Germany and MDACC with fludarabine or fludarabine- based
regimens did not benefit the patient over the age of 65 or 70. As the median
age of diagnosis is 72, the development of safe, active therapies for older
patients is an unmet need in CLL. Lenalidomide is an active drug in CLL.
The current clinical trial was designed to assess whether low-dose continuous
lenalidomide therapy can provide long-term disease control with
minimum toxicity in patients older than 65. Methods: Patients initiate
lenalidomide at 2.5mg daily (28-day cycle) and only dose escalate for
progressive disease (POD). Results: 18 patients have been enrolled: 12 men
and 6 women, med age 70 (range 65-84) with Rai-intermediate (7 pts) or
high-risk (11 pts; 61%) disease; med WBC 50.5 (6.7-326.3), HGB 10.3
(8.9-13.9), PLT 121 (44-215), �-2 microglobulin 4.9 (3.0-10.2). 16
(89%) patients had chromosomal abnormalities: 3 with 13q, 6 with tris 12,
3 with 11q, and 4 with 17p. 13 (72%) patients have unmutated IGHV. 5
(28%) patients were previously untreated; 13 (72%) had prior therapy
(range 1-5; med 2). Median dose of lenalidomide is 2.5mg (range
2.5mg-10mg); median no. cycles is 7 (range 1-28). 11 patients (61%) are
still on therapy (7 previously treated): 6 at 2.5mg; 4 at 5mg, and 1 at
10mg. 7 have discontinued therapy: 1 for ITP; 3 for POD including one with
Richter’s, 2 for desquamating rash; and 1 withdrew consent. Only 2
patients had tumor lysis and 10 had tumor flare (8 given steroids briefly). In
these older patients on long-term continuous treatment, therapy has been
generally well tolerated. There have been no deaths on study. Pneumonia
developed in 4 patients (3 of these had prior therapy). 1 patient with history
of atrial fibrillation developed DVT/PE. Main hematologic toxicity is
neutropenia seen in 11 patients but transient. Grade 3/4 thrombocytopenia
and anemia was seen in 5 and 0 patients, respectively. Conclusions:
Low-dose continuous lenalidomide therapy iappears to be well-tolerated
and may offer long term disease control in some patients with CLL.
Additional accrual and longer follow-up will be required to further assess
the utility of this strategy.
6611 General Poster Session (Board #23F), Mon, 1:15 PM-5:15 PM
Disease response and survival outcomes in acute myeloid leukemia (AML)
patients unfit for chemotherapy treated with 10-day decitabine as initial
therapy. Presenting Author: Theodore Stewart Gourdin, University of
Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD
Background: AML is primarily a disease of older adults, with a median age of
67 years at diagnosis. Many patients are considered unfit for chemotherapy
due to poor performance status and/or comorbidities, prompting investigation
of less intensive approaches. A clinical trial in which 10-day courses of
decitabine 20mg/m2 were given every 28 days as initial therapy demonstrated
a promising complete remission (CR) rate and disease-free survival
(DFS). We used this regimen to treat AML patients unfit for chemotherapy
outside of a clinical trial. Methods: Charts of 32 newly diagnosed AML
patients treated with 10-day courses of decitabine 20mg/m2 as initial
therapy at the University of Maryland Greenebaum Cancer Center between
September 2010 and November 2011 were retrospectively reviewed. If
patients attained bone marrow blasts �5%, 5-day courses were administered
subsequently and were continued until disease progression. Results:
Median age at diagnosis was 74 years (range, 52-86). 18 patients were
male and 14 female. 23 were Caucasian, 7 African-American and 1
Hispanic. 10 patients (31%) had performance status � 2. All had
significant cardiac, pulmonary and/or renal disease. Karyotype risk group
was unfavorable in 17 patients, intermediate in 14 and unknown in one.
There were 9 CRs and 1 partial remission, for an overall response rate of
31%, following a median of 2 (range, 1 to 4) courses. 21 patients did not
respond to treatment following 1 to 6 courses, and one died within 29 days
of treatment initiation. 21 patients (65%) were hospitalized at least once
for fever or infection during treatment. Of the 9 patients who achieved CR,
5 had normal, 3 complex and 1 unknown karyotypes. Median DFS was 390
days (range, 87�-468�) and median OS 180 days (range, 15-623�).
Six-month OS was 37.5% and 1-year OS 16.5%. Conclusions: AML
patients unfit for chemotherapy treated with 10-day decitabine 20mg/m2
outside of a clinical trial had a higher response rate than reported for 5-day
decitabine, but a lower response rate than in the reported clinical trial of
the 10-day regimen. Additional novel treatment approaches are needed for
these patients.
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