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anthracyclines in vitro. A favorable impact on the dismal clinical course of acute
myeloid leukemia (AML) was suggested (Schlenk et al. ASH 2008). Recently, a phase
I/II trial assessing the efficacy and safety of two schedules of Bel in patients unfit for
intensive induction therapy has shown anti-leukemic effect both of Bel alone and in
combination with idarubicin (ClinicalTrials.gov ID: NCT00878722).
We evaluated the role of cytogenetic aberrations on response to Bel therapy in 41
patients (pts), of whom cases with intermediate risk cytogenetics in trend responded
better to Bel than patients with high risk cytogenetics (p = 0.14). Five complete
remissions (CR) and 2 partial remissions (PR) were observed in 25 pts (28%) AML
cases with low/intermediate risk cytogenetic aberrations, whereas no CR and 2 PR
were seen in 16 pts (13%) high risk AML cases.
Gene expression profiling based on 13 pts (4 CR + PR and 9 PD) revealed a strong
gene expression pattern associated with the response to Bel. MLL, a gene well known
to be involved in epigenetic deregulation, was among the top 20 strongest
correlations. Furthermore, differential expression of TP53 was also of special interest
as histone deacetylases have been shown to modulate p53 transcriptional activity. In
accordance, gene ontology class comparison analysis showed a significant enrichment
of categories associated with epigenetic regulation such as “histone methyltransferase
activity” and “histone deacetylase activity”. In addition, the respective gene
expression pattern harbored predictive information as based on an in vitro cell line
derived predictor and a blinded Bel response prediction was feasible.
A trend indicating the potential association of Bel response and intermediate risk
cytogenetics AML has been found. High risk AML cases might also benefit from an
epigenetic treatment approach with a HDACi. Further randomized studies are
warranted to explore the benefit of Bel in pts with AML.
Disclosure: S. Knudsen: MPI EmployeeJ. Tjørnelund: Employment Topotarget. All
other authors have declared no conflicts of interest.
1069PD PREDICTING RESPONSE RATES OF HIGH GRADE NON
HODGKIN’S LYMPHOMA: A COMPARATIVE STUDY OF
INTERNATIONAL PROGNOSTIC INDEX (IPI) WITH
SUBJECTIVE GLOBAL ASSESSMENT (SGA)
V.S. Ostwal 1 , P. Bagayatkar 2 , P. Pawaskar 1 , R. Thippeswamy 1 , M. Sengar 1 ,
H. Menon 1 , N. Khattry 1 , B. Bagal 1 , R. Nair 1 , M.K. Mallath 3
1 Medical Oncology, Tata Memorial Hospital Centre, Mumbai, INDIA, 2 Medical
Oncology, Tata Memorial Hospital, Mumbai, INDIA, 3 Digestive Diseases, Tata
Memorial Hospital Centre, Mumbai, INDIA
Introduction: Malnutrition is common in patients with cancer and no study has corelated
the effect of malnutrition on outcomes of non Hodgkins Lymphoma (NHL)
from India. Besides, there are no studies validating the international prognostic index
(IPI) from India. This study was done to compare the prognostic abilities of IPI and
subjective global assessment (SGA) for early outcomes in NHL.
Methods: This is a prospective observational study set in the lymphoma clinic of
Tata Memorial Hospital, Mumbai between January to December 2010. All patients
were screened for malnutrition at entry using a modified SGA tool. Baseline clinical
factors of prognostic importance including IPI scores were recorded. Univariate and
multivariate comparison were made using SPSS or EpiInfo 2000 software.
Results: There were 401 patients with high grade NHL. The analysis of 389 patients
with all information available showed that the IPI scores were low risk, low
intermediate risk, intermediate high risk, high risk in 133 (34.3%), 95 (24.4 %), 91
(23.4%) and 70 (17.9 %) patients respectively. The SGA scores were A, B, and C in
188 (48.6%), 129 (33.2%) and 72 (18.2 %) patients respectively. Early outcomes
included CR in 241 (62.6 %), EFS in 73% and overall survival in 81% patients at
1-year. Univariate analysis revealed that the SGA scores were significantly associated
with the IPI variables - age, serum LDH, performance status (ECOG), stage (Ann
Arbor), extranodal sites as well as hemoglobin, response rates, one year survival and
disease progression. Multivariate analysis revealed that SGA was a highly significant
independent predictor of all early outcome parameters. Some IPI scores lost
significance in the multivariate model.
Conclusions: The SGA is a highly significant and independent predictive biomarker
(for CR) and a prognostic biomarker (for 1-year OS and PFS) with good
discriminative function in patients with NHL.
Disclosure: All authors have declared no conflicts of interest.
1070PD RELATIONSHIP BETWEEN PROGRESSION-FREE SURVIVAL
AND OVERALL SURVIVAL IN CHRONIC LYMPHOCYTIC
LEUKEMIA
C. Beauchemin 1 , J.B. Johnston 2 , M. Lapierre 1 , F. Aissa 3 , J. Lachaine 1
1 Faculty of Pharmacy, University of Montreal, Montreal, QC, CANADA, 2 Cancer
Research, Manitoba Institute of Cell Biology, Winnipeg, MB, CANADA, 3 Market
Access and Health Outcome Department, Lundbeck Canada Inc., Montreal, QC,
CANADA
Objectives: Overall survival (OS) represents a universally recognized measure to
evaluate clinical benefits for a new anti-cancer drug. Due to the limitations of this
measure of survival, surrogate endpoints are frequently used, such as progression-free
Annals of Oncology
survival (PFS) and time-to-progression (TTP). However, the surrogacy of these
endpoints for OS is not validated in all cancer settings. The main objective was to
evaluate the relationship between median PFS/TTP and median OS in the context of
chronic lymphocytic leukemia (CLL) using a trial-based approach.
Methods: A systematic review of the literature was conducted using the PICO method:
Population consisted of patients with CLL; Interventions and Comparators (when
applicable) were standard therapies for CLL and Outcomes were median PFS/TTP and
median OS. Two independent reviewers screened titles, abstracts, and full papers for
eligibility, and then extracted data from selected studies. Correlation coefficient was
calculated to assess the relationship between median PFS/TTP and median OS.
Subgroup correlation analyses were also conducted according to characteristics of
selected studies such as line of treatment and type of treatment under investigation.
Results: Among the 1,263 potentially relevant studies identified by the literature
search, 23 articles were included. The mean number of patients included in these
studies was 118 patients (min: 30, max: 724). The median age was 63.0 years and the
median follow-up period was 33.7 months. On average, median PFS/TTP was 14.0
months (sd =12.4) and median OS was 35.0 months (sd = 31.2). The results of the
correlation analysis demonstrated that median PFS/TTP is highly correlated with
median OS, with a Spearman’s correlation coefficient of 0.813 (p ≤ 0.001). A
significant correlation between median PFS/TTP and median OS was observed in the
second-line and subsequent-line therapy, but not in the first-line setting.
Conclusion: The present results demonstrate a very strong correlation between
median PFS/TTP and median OS in the context of CLL, which reinforce the
hypothesis that PFS/TTP would be adequate surrogate endpoints for OS in this
cancer setting. These findings would strongly support the use of PFS/TTP in the
appreciation of the clinical efficacy of new drugs in CLL.
Disclosure: All authors have declared no conflicts of interest.
1071P 3D TELOMERE SIGNATURES OF HODGKIN-CELLS AT
DIAGNOSIS IDENTIFY PATIENTS WITH POOR RESPONSE
TO CONVENTIONAL CHEMOTHERAPY
H. Knecht 1 , N. Kongruttanachok 2 ,B.Sawan 3 , J. Brossard 4 , S. Prévost 5 ,
É. Turcotte 5 , Z. Lichtensztejn 2 , D. Lichtensztejn 2 , S. Mai 2
1 Haematology, CHUS, Sherbrooke, QC, CANADA, 2 MICB, Unversity of
Manitoba, Winnipeg, MB, CANADA, 3 Pathology, CHUS, Sherbrooke, QC,
CANADA, 4 Pediatrics, CHUS, Sherbrooke, QC, CANADA, 5 Medical Imaging,
CHUS, Sherbrooke, QC, CANADA
In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and
multinuclear Reed-Sternberg (RS) cells are characterized by a distinct 3D nuclear
telomere organization with shortening of the telomere length and the formation of
telomeric aggregates. We asked if the severity of these telomere changes correlates
with clinical behaviour of the disease. We evaluated (mainly prospectively) the 3D
telomere organization by quantitative fluorescent in situ hybridization (Q-FISH) on
diagnostic biopsies from 20 patients who were good responders and compared them
with 20 diagnostic biopsies of 11 patients with refractory or relapsing HL (11 initial
biopsies, five confirming progressions and four confirming relapses). The H-cells from
patients with refractory/relapsing disease contained a significantly higher percentage
of very small telomeres (p < 0.05) and telomere aggregates (p < 0.05) compared with
H-cells of patients entering rapid remission. In order to eliminate therapy related
changes of the 3D nuclear telomere organization we compared (prior to any
treatment) 10 initial diagnostic biopsies of refractory/relapsing HL with diagnostic
biopsies of 10 patients with ongoing long lasting remission (mean 51 months).
Importantly, the differences between both groups were highly significant (p < 0.005)
for very small telomeres and for aggregates (p < 0.02). Since both groups were treated
with standard ABVD chemotherapy, long lasting remission or progression/relapse are
independent of the choice of chemotherapy and have to rely on intrinsic factors of the
tumour cells. Thus, H-cells of refractory/relapsing HL are characterized by a specific
3D telomere signature, i.e. abundant very small telomeres. 3D telomere Q-FISH
identifies these highly aggressive mononuclear H-cells at the first diagnostic biopsy
and thus may offer a novel molecular tool to optimize initial treatment.
Disclosure: All authors have declared no conflicts of interest.
1072P RECRUIT-TANDAB AFM13 - OVERCOMING LIMITATIONS OF
MONOCLONAL ANTIBODIES IN HODGKIN LYMPHOMA
E. Zhukovsky 1 , M. Ravic 2 , A. Rothe 3 , M. Topp 4 , A. Younes 5 , S. Knackmuss 6 ,
U. Reusch 6 , E. Rajkovic 6 ,C.Hucke 2 , M. Little 6
1 Affimed Therapeutics AG, Heidelberg, GERMANY, 2 Clinical Department, Affimed
Therapeutics AG, Heidelberg, GERMANY, 3 Klinikum D.Universität zu Köln Klinik
f. Innere Medizin I, University of Cologne, Cologne, GERMANY, 4 GSLS,
University of Wuerzburg, Med. Klinik und Poliklinik II Immun- und Gentherapie,
Wuerzburg, GERMANY, 5 Department of Lymphoma/Myeloma, University of
Texas M.D. Anderson Cancer Centre, Houston, TX, UNITED STATES OF
AMERICA, 6 Research, Affimed Therapeutics AG, Heidelberg, GERMANY
AFM13 is a RECRUIT-TandAb (CD30xCD16A) for treating Hodgkin Lymphoma by
recruiting NK-cells and macrophages to the specific CD30 surface antigen on
ix350 | Abstracts Volume 23 | Supplement 9 | September 2012