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

6600 General Poster Session (Board #22C), Mon, 1:15 PM-5:15 PM
Real-world study of imatinib treatment patterns and outcomes among
veteran patients with chronic myeloid leukemia. Presenting Author: Lizheng
Shi, Tulane University, New Orleans, LA
Background: Imatinib (IM) is the most commonly used drug in the treatment
of chronic myeloid leukemia-chronic phase (CML-CP) patients (pts). This
study investigated the treatment patterns and outcomes for veteran
CML-CP pts initiated on IM. Methods: Pts (age �18 yrs) with �1 CML
diagnosis codes documented (ICD-9 CM: 205.1x) between 1/1/2000 and
12/31/2010 were identified from the VISN 16 data warehouse. Pts were
required to have initiated IM as the first-line therapy in CML-CP. Accelerated
and blastic phases (A/BP) were identified based on WHO classification
using CBC information. IM dose adjustments were assessed as dose
increase from �400 mg to �600mg or from 400-600mg to �800 mg
daily. Rates of IM discontinuation (no use of IM for �60 days) and
switching to other drug therapy (dasatinib/nilotinib (DS/NL), hydroxyurea,
and interferon-alpha) were estimated. Time to discontinuation, progression
to A/BP, and survival were assessed using Kaplan-Meier analysis (K-M).
Overall survival was measured from IM initiation while survival among pts
with disease progression was measured from the date of progression.
Results: Among the 137 pts selected, average age was 64.8 yrs and
follow-up time was 4.0 yrs. 16.8% of pts had dose increase from �400mg
to �600mg and 21.7% of these pts switched to other therapy after dose
increase. 13.1% of pts had dose increase from 400-600mg to �800 mg
with 22.2% of these pts switching to other therapy later. During the study,
83.8% of the 74 pts who discontinued IM did not use other drug therapies;
and 16.2% (12 pts) switched, among which 9 pts took DS/NL. K-M showed
that 25.6% and 42.4% pts discontinued IM treatment by year 1 and 2 and
8.1% and 16.0% pts experienced disease progression by year 1 and 2,
respectively. Among the 28 patients who had disease progression, 32.1%
continued IM use after progression and only 7.1% switched to other
therapies (50% switching to DS/NL). The mortality rates were 3.0% and
9.5% by year 1 and 2 after IM initiation, and 21.7% and 42.7% by year 1
and 2 after disease progression, respectively. Conclusions: The majority of
IM-treated patients, including patients with disease progression, discontinued
IM use without switching to other effective therapies.
6602 General Poster Session (Board #22E), Mon, 1:15 PM-5:15 PM
A phase II study of clofarabine and daunorubicin in patients age 60 or older
with newly diagnosed adult acute myeloid leukemia. Presenting Author:
Carlos Enrique Vigil, Roswell Park Cancer Institute, Buffalo, NY
Background: The outcome of acute myeloid leukemia (AML) patients (pts)
�60 years (yrs) old remains poor, with a median overall survival of a few
months. Neither the addition of other drugs during induction of the
traditional 7�3 regimen nor an increase of cytarabine or daunorubicin
doses has improved their overall survival. We have therefore designed a
combination of clofarabine and daunorubicin. Aims: Determine the safety
and efficacy of clofarabine and daunorubicin in pts � 60 yrs of age.
Methods: Induction-clofarabine 20 mg/m2 /d in a 1-hour IV for 5 days
followed 3 hrs later by daunorubicin 50 mg/m2 IV over 5 minutes on days 1,
3, and 5. Pts who did not achieve complete remission (CR) or CR without
platelet recovery (CRp) were eligible for a second round of induction as
above. Consolidation - 2 cycles of clofarabine 20mg/m2 /d for 3 days and
daunorubicin 50 mg/m2 /day on days 1 and 3. Results: Twenty-one pts were
enrolled. The median age was 69 (range 60-85) yrs. Seven pts (34%) had
secondary AML and 52% had complex karyotype. Twenty-one pts completed
one induction cycle, one pt received a second induction due to
residual disease and 6 pts underwent consolidation therapy. The principal
toxicity was grade �3 infections and prolonged thrombocytopenia and
neutropenia, which occurred in 18% and 21% of pts, respectively. Three
deaths were documented from treatment complications (sepsis and fungal
infections). Eight (38.1%) pts achieved either a CR or CRp. Responses
were observed in 5/11 (45.5%) pts with high risk features (complex
karyotype and/or presence of FLT3). The median disease free-survival was
1.9 (range, 0.9-8) months and the median overall survival was 6.5 (range,
4.2-14.2) months. The 1-yr overall survival was 35%. Conclusions: These
preliminary results suggest that clofarabine in combination with daunorubicin
is safe, well-tolerated with minimal toxicity, and active for the upfront
treatment of �60 yrs old AML pts, including those with adverse features.
Future trials will explore additional modifications to this regimen in order to
optimize therapy for this group of pts with high risk features and frequent
treatment failure.
Leukemia, Myelodysplasia, and Transplantation
441s
6601 General Poster Session (Board #22D), Mon, 1:15 PM-5:15 PM
A comparison of CR versus CRi response following CPX-351 treatment of
newly diagnosed AML in elderly patients (pts). Presenting Author: Jeffrey E.
Lancet, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Background: A Phase 2b study randomized untreated elderly AML pts to
CPX-351 or 7�3. CPX-351 improved leukemia clearance (88% v 71%,
�5% marrow blasts), CR�CRi rate (67% v 51%), and was particularly
effective in pts with adverse karyotype and antecedent hematologic
disorders (sAML). Survival following CRi is usually inferior compared to CR.
CPX-351 markedly prolongs plasma drug levels and maintains the 5:1
molar ratio for optimal leukemic cell killing potentially delaying hematologic
recovery among CRi patients. Consequently, we compared the
characteristics and outcomes of pts achieving CR v CRi. Methods: Untreated
AML pts, aged 60-75, PS� 0-2, SCr � 2.0 mg/dL, total bilirubin
�2.0 mg/dL, ALT/AST �3 x ULN, and LVEF �50% were eligible. Pts were
randomized 2:1 to receive up to 2 inductions and 2 consolidations with
CPX-351 (100 u/m2 ; D 1, 3, 5; 90 min infusion) or 7�3 (cytarabine�100
mg/m 2
and daunorubicin�60 mg/m2 ). Consolidation with stem cell transplantation
(SCT) was permitted. The 1o endpoint was CR�CRi rate. The
7�3 control arm had only a single CRi among 21 responders. The CPX-351
arm had 15 CRi (27%) and 41 CR (73%) allowing a CR v CRi comparison to
be made. Results: CR and CRi pts were balanced by age, race, and PS. The
CRi group had more males (87% v 51%), more baseline WBC�20K (27% v
15%), and more adverse karyotype (40% v 27%) and sAML (47% v 29%).
A smaller proportion of CRi pts received post-remission chemotherapy
(47% v 73%) but had similar rates of SCT (13% v 20%). Most CRi pts had
delayed platelet recovery (80%). By 1-year more CRi pts had relapsed
(54% v 39%) and more had died (54% v 34%). Contributing causes
included: relapsed AML (7 CRi v 10 CR pts), complications post SCT (1 CRi
v 1 CR pt), chemotherapy complications (0 CRi v2CRpts) and unknown
causes (0 CRiv1CRpt). The survival curves were not significantly different
(p�0.39). Conclusions: More CRi patients had adverse karyotype and sAML
and most (53%) received no post remission chemotherapy. Survival was
not significantly different compared to CR patients but was markedly better
than that of non-responders. These data suggest that CRi following
CPX-351 provides clinically meaningful benefit, a finding that needs to be
confirmed in a larger randomized study.
6603 General Poster Session (Board #22F), Mon, 1:15 PM-5:15 PM
Factors associated with outcome of secondary MDS and AML: Review of
2,182 patients at MDACC. Presenting Author: Francesco Paolo Tambaro,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Secondary acute myeloid leukemia (sAML) and myelodysplastic
syndromes (sMDS) have been associated with prior treatment for other
malignancies, particularly chemotherapy, and associated with high-risk
features and poor clinical outcomes. Methods: We identified 2,182 patients
(pts) (57% male) diagnosed with AML (n�1,073; all FAB/WHO represented)
or MDS (n�1,109; 984 MDS, 125 MDS/MPD, all WHO represented)
and who had 1 (n�1,907), 2 (n�239), or 3 (n�36) prior
malignancies (PM). Pt characteristics and outcomes were analyzed. Results:
The median age was 67 yrs. Prior hematological neoplasms (25%), breast
(16%), prostate (16%), skin (9%) were most common. The prior malignancy
reflected prior treatment, 1,252 pts underwent surgery, 939
received radiation, and 1,211 received chemotherapy alone or in combination;
124 were untreated. Types of prior malignancy and prior treatment
associated with AML and MDS will be presented. Median time to AML/MDS
was 64 months (mo) and 46 mo (p�0.000) for pts with 1 or �1 PM,
respectively, and correlated with type of PM (p�0.000) and previous
monotherapy (surgery vs RT vs chemo) (p�0.020). For both AML and MDS,
the incidence of poor-risk cytogenetics was nearly twice for pts who
received prior chemotherapy compared to those who underwent surgery or
radiation alone. Factors associated with survival in secondary AML and
MDS are reported in the table. Conclusions: In conclusion, outcomes for pts
with secondary AML and MDS are poor, especially for pts treated with prior
chemotherapy. Type of prior malignancy and treatment are correlated with
outcomes. Furthermore, greater number of prior malignancies correlates
with inferior outcomes.
AML MDS
Variable
Survival (mo) p Survival (mo) p
#PM 1vs�1 8.6 vs 5 0.004 13.5 vs 10.3 .012
Type prior malignancy Kidney vs lung 12 vs 4 0.00 19.2 vs 9.8 .000
Prior treatment Surgery vs RT vs Chemo 11.7 vs 5 vs 3.5 0.000 19 vs 18 vs 12 .003
Prior treatment Chemo vs No Chemo 10.1 vs 6.7 0.002 18.3 vs 11 .000
Karyotype Bad vs Int vs Good 4.7 vs 12 vs 58.6 0.000 8.9 vs 21 vs 26
Prior hematologic
malignancy
No vs Yes 8.6 vs 6.8 0.08 13.6 vs 11.1 .03
FAB M3 vs M1 61 vs 4 0.000 NA
IPSS High vs Int-1 vs Int-2 vs Low NA NA 7.6 vs 18 vs 9.7 vs 34.7 .000
# cytopenias 0 vs 1 vs 2 vs 3 NA NA 15 vs 16.7 vs 9.6 vs 6.2 .000
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