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

6592 General Poster Session (Board #21C), Mon, 1:15 PM-5:15 PM
Phase II study of omacetaxine (OM) and low-dose AraC (LDAC) in older
patients with acute myelogenous leukemia (AML) and high-risk myelodysplastic
syndrome (MDS). Presenting Author: Tapan M. Kadia, University of
Texas M. D. Anderson Cancer Center, Houston, TX
Background: Treatment of AML in patients (pts) � 70 yrs of age with
intensive chemotherapy is associated with high rates of early mortality and
little benefit. Newer, lower-intensity approaches with novel mechanisms
are needed. OM is a semisynthetic plant alkaloid which has demonstrated
activity in AML as a single agent and with chemotherapy. Methods: We
studied a low intensity program combining subcutaneous (SQ) OM with SQ
LDAC in pts �/� 60 yrs, with AML or MDS, a performance status (PS) of
�/�2, and adequate organ function. Initially, 6 pts were enrolled at the
following doses: OM 1.25 mg/m2 SQ Q12 hrs x 3 days with AraC 20 mg SQ
Q12 hrs x 7 days on a 4 week cycle. If safety is confirmed, the phase II
portion would commence at the safe dose levels. Up to 12 courses can be
given. The primary endpoint was to determine the complete remission (CR)
rate. Secondary endpoints were: CR duration, DFS, OS, safety, and early
mortality. Results: 17 pts were enrolled on study so far. The median age was
74 yrs (range, 64-81); the median PS was 1 (0-1). The karyotypes in these
pts were: diploid in 6 (35%), complex with chromosome (chr) 5 and/or 7
abnormality (abnl) in 4 (24%), complex without chr 5 and/or 7 abnl in 2
(12%), 11q abnl in 1 (6%), poor metaphases in 1 (6%), and other in 3
(18%). Four pts with prior MDS were treated with a median of 2 prior
therapies (1-3). Median bone marrow blast % at the start of therapy was 40
(15-87). The median WBC, hemoglobin, and platelets were 2.1 (0.4–
24.8), 8.9 (7.7–10.7), and 45 (14–104), respectively. These pts have
received a median of 1 (1-3) cycle of therapy. Of the 11 pts evaluable for
response, there were 2(18%) CR, 1(9%) CRp, 1(9%) PR for an ORR of
4/11 (36%). Five pts had no response and were taken off study. Two pts
died on study: 1 on day 6 and 1 on day 27. Both pts were 74 yrs with a
complex karyotype. One died of pneumonia and multi-organ failure and the
2nd died from cardiac arrest. Other than the deaths, serious adverse events
included grade 3 transaminitis in 1 and grade 3 heart failure in 1.
Conclusions: OM and LDAC appears to be tolerable in older pts with AML.
The combination appears to have activity. Stopping boundaries for futility
and safety have not been breached. Enrollment is ongoing.
6594 General Poster Session (Board #21E), Mon, 1:15 PM-5:15 PM
Monitoring and switching patterns in chronic myelogenous leukemia (CML)
pts treated with imatinib (IM): A chart review analysis. Presenting Author:
Lei L. Chen, Novartis Pharmaceuticals, East Hanover, NJ
Background: The objective of this study is to evaluate compliance to
National Comprehensive Cancer Network (NCCN) and European LeukemiaNet
(ELN) guidelines regarding monitoring frequency and switching
practices in CML patients (pts) treated with IM in community practices.
Methods: Physicians treating CML pts were selected from 28 community
practices throughout the USA. Each physician reviewed and extracted up to
15 pt charts of CML pts in chronic phase not previously enrolled in clinical
trials. Pts were required to have initiated 1st-line IM between 1/2006 -
10/2010. Data on 1st-line IM treatment response monitoring frequency
and outcomes, and corresponding therapy switching patterns were extracted.
Results: Information was collected on treatment monitoring and
response from a total of 297 pt charts. Median IM duration was 320 days.
Percentages of pts monitored according to both guidelines are reported. In
addition, the proportion of pts who missed milestones and the proportion of
pts who did not switch to a 2nd-line tyrosine kinase inhibitor (TKI) when
they missed milestones are reported. Conclusions: There is considerable
undermonitoring of CML pts receiving IM, which is likely to result in a
significant portion of pts with suboptimal response left undetected. The
switching rate to 2nd-line TKI among pts with suboptimal response to IM is
much lower than recommended by either NCCN or ELN guidelines.
Milestone
Mos Response % Monitored
% Missed the
milestone (among
monitored pts)
% Switched to
2nd-line TKI
(among pts who
missed milestone)
0-3 CHR †‡ 4-6 PCyR
(N�297) 98.7 10.2 16.7
†‡ 7-12 CCyR
(N�285) 60.4 11.6 5.0
†‡ 13-18 CCyR
(N�284) 61.3 29.9 17.3
† Pts previously achieved CCyR (N�145) 39.3 1.8 0.0
Pts did not achieve CCyR* (N�119) 38.7 32.6 33.3
19-24 Pts previously achieved CCyR (N�172) 36.6 3.2 0.0
Pts did not achieve CCyR* (N�73) 13.7 30.0 33.3
25-30 Pts previously achieved CCyR (N�156) 23.7 2.7 100.0
Pts did not achieve CCyR* (N�83) 7.2 50.0 66.7
31-36 Pts previously achieved CCyR (N�158) 22.8 2.8 100.0
0-12 MMR
Pts did not achieve CCyR* (N�77) 5.2 25.0 0.0
‡ (N�297) 71.7 28.6 9.8
13-18 (N�264) 72.7 13.0 12.0
19-36 (N�245) 71.8 9.7 23.5
† NCCN; ‡ ELN; * Did not achieve CCyR/not previously monitored.
Leukemia, Myelodysplasia, and Transplantation
439s
6593 General Poster Session (Board #21D), Mon, 1:15 PM-5:15 PM
Prognostic and predictive significance of smudge cell percentage on
routine blood smear in chronic lymphocytic leukemia patients: A single
center study from northern India. Presenting Author: Ajay Gogia, AIIMS,
New Delhi, India
Background: Smudge cells are ruptured lymphocytes seen on routine blood
smears of chronic lymphocytic leukemia (CLL) patients. We evaluated
prognostic and predictive significance of smudge cells percentage on a
blood smear in CLL patients. Methods: We calculated smudge cell percentages
(ratio of smudged to intact cells plus smudged lymphocyte) on
archived blood smears of 185 untreated CLL patients registered at I.R.C.H,
AIIMS, New Delhi over a period of 11 years. Results: There were 135 males
and 50 females. The median age was 60 years (28-89). Median absolute
lymphocyte count was 42 X109 /L. Clinical Rai stage distribution was: stage
0 - 10%, stage I - 15%, stage II - 40%, stage III -15 % and stage IV - 20%.
The median smudge cells percentage was 27% (4% to 76%). There was no
correlation of proportion of smudge cells with age, sex, lymphocyte count,
organomegaly, ZAP 70 � or CD 38 � CLL patients, but there was
significant correlation with stage of disease. Median smudge cell percentage
in stage 0 & I -33% (12-76), stage II- 31% (12-61) and stage
III&IV-21% (4-51) [ p��0.001]. One third of early stage (0, I &II) patients
required treatment during follow up, at the end of 5 years of follow up 55%
required treatment with smudge cell � 30%, against 24% patients
requiring treatment with smudge cells � 30% [p�0.01]. The percentage of
smudge cells as a continuous variable correlated with OS [HR 0.96, p�
0.001]. The 5-year survival rate was 51% for patients with 30% or less
smudge cells compared with 81% for patients with more than 30% of
smudge cells. Thirty percent of patients died during follow up. Median OS
was 5 years with median follow up period of 3.9 years. Smudge cells
percentage (�30% vs. �30%) had significant association with OS [HR
0.47, 95%CI (0.32-0.71), p�0.001)]. Conclusions: Simple and inexpensive
detection of smudge cells on blood smears on routine diagnostic test
useful in predicting progression free and OS in CLL patients and may be
beneficial in countries with limited recourses.
6595 General Poster Session (Board #21F), Mon, 1:15 PM-5:15 PM
Treatment outcome of acute myeloid leukemia (AML) in HIV� patients.
Presenting Author: Irene Ang Dy, Leukemia Program, Continuum Cancer
Centers of New York, New York, NY
Background: AML is diagnosed more frequently in HIV� patients than
previously. The results with standard AML treatment in such patients have
not been evaluated. We evaluated whether the results justify standard
aggressive treatment of AML in HIV� patients. Methods: We identified 5
HIV� patients at our institution who were subsequently diagnosed with
AML and 68 previously reported HIV� patients with AML through PubMed
from 1986-2011. The median age at the time of AML diagnosis was 40
years (range 7-70 years). Of the 26 patients with known karyotype, 7 had
favorable, 7 intermediate and 12 had unfavorable cytogenetics. The
majority of treated patients received standard intensive induction therapy
and complete responders (CR) received consolidation therapy. HIV was
pre-, post-, and concurrently diagnosed in 47, 2 and 19 AML patients
respectively. The Kaplan-Meier method examined whether CD4 count, AML
treatment and CR attainment affected overall survival. Cox proportional
hazard modeling, adjusted for age and CD4 count determined whether AML
treatment and CR attainment were associated with death from AML.
Results: The final analysis included pre- and concurrently HIV diagnosed
AML patients (n�66). HIV infection occurred at a median of 5 years (range
0.25-28 years) prior to the diagnosis of AML in 47 patients. The most
common FAB types were M4 (22.6%) and M2 (22.6%). CR was achieved in
71.7% (n�33/46) of treated patients and 51.5% (n�17/33) of them
relapsed with a median CR duration of 9.2 months. Median survival of
patients with CD4 count � 200 and � 200 was 7 vs. 13.4 months
(p�0.03); median survival of untreated and treated patients was 1.0
vs.13.2 months (p � 0.001) and median survival of treated patients who
did and did not achieve CR was 2 vs. 21 months respectively (p � 0.001).
All treated patients and those who achieved CR were less likely to die from
AML than untreated patients and those who failed to respond (H.R�0.05;
95% CI, 0.01-0.17 and H.R. � 0.11; 95% C.I, 0.04-0.35, respectively).
Conclusions: Standard AML treatment and CR were associated with longer
survival in HIV� patients regardless of CD4 count. More than half of
patients studied achieved CR. HIV� AML patients should be offered
standard AML therapy.
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