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

524s Lymphoma and Plasma Cell Disorders
8057 General Poster Session (Board #33F), Mon, 1:15 PM-5:15 PM
Phase I study cohort evaluating an optimized administration schedule of
SAR3419, an anti-CD19 DM4-loaded antibody drug conjugate (ADC), in
patients (pts) with CD19 positive relapsed/refractory b-cell non-Hodgkin’s
lymphoma (NCT00796731). Presenting Author: Bertrand Coiffier, Hospices
Civils de Lyon Sud, Pierre-Bénite, France
Background: The recommended dose (RD) of SAR3419 administered
intravenously every 3 weeks (q3w) for 6 cycles is 160 mg/m2 and is 55
mg/m2 when administered weekly (q1w) for 8-12 doses. Reversible corneal
deposits were dose limiting (DLT) in the q3w schedule. The q1w schedule
was well tolerated and active. However, based on the occurrence of
late/cumulative adverse events (AE) at the RD supported by pharmacokinetic
(PK) analyses showing ADC plasma accumulation after 4 weekly
doses, an optimized schedule consisting of 4 weekly doses followed by 4
bi-weekly doses at the RD was tested. Methods: The q1w study was
extended to treat 25 pts with the optimized schedule for 8 to 12 doses.
Results: Twenty-one pts were evaluable. Main histologies were diffuse large
B-cell (DLBCL) (9; 43%) and follicular (6; 29%). Median number of prior
regimens was 2 [1-8], 6 pts received prior autologous transplantation and
95% of pts were Ann Arbor stage III-IV at study entry. Median number of
doses received was 8 as planned with a median relative dose intensity of
1.0 [0.8-1.0]. Most frequent AEs were asthenia (1 pt with grade 3) and
gastrointestinal disorders in 7 pts each. No AE fulfilled the defined DLT
criteria. Reversible grade 1 blurred vision/corneal event occurred in 1 pt.
Grade 3-4 haematological toxicities were minor consisting of non complicated
neutropenia in 4 pts, thrombocytopenia in 2 pts and anemia in 1 pt
with no transfusion support. Six (29%) pts, among them 3 with DLBCL,
achieved an objective response including 3 CRu (1 in a pt refractory to last
regimen). In addition, 9 (43%) pts had stable disease. Response duration
was [8-35�] weeks, 5 pts still responding at the cut-off date. Conclusions:
The optimized administration schedule shows an improved safety profile
compared to prior tested schedules. The clinical efficacy is preserved
essentially in aggressive lymphoma. The optimized schedule is being
assessed in 2 phase II studies evaluating SAR3419 either as a single agent
or in combination with rituximab in pts with DLBCL histology.
8059 General Poster Session (Board #33H), Mon, 1:15 PM-5:15 PM
High affinity CD3 RECRUIT TandAb for T cell-mediated lysis of CD19� tumor B cells. Presenting Author: Eugene Zhukovsky, Affimed Therapeutics
AG, Heidelberg, Germany
Background: CD19 is expressed from early B cell development to the
differentiation into plasma cells and is an attractive target for B cell
malignancies either lacking CD20 expression or refractory to anti-CD20
antibody therapies. T cells are potent tumor killing effector cells that are
not recruited by native antibodies. The CD3 RECRUIT-TandAb AFM11, a
human bispecific tetravalent antibody with two binding sites for both CD3
and CD19, is a novel therapeutic for the treatment of NHL that harnesses
the cytotoxic nature of T cells. Methods: A bispecific anti-CD19/anti-CD3
tetravalent TandAb with humanized and affinity matured variable domains
was constructed. The TandAb’s binding, T-cell mediated cytotoxic activity,
and cytokine release were characterized in a panel of in vitro assays. In vivo
efficacy was evaluated in a murine NOD/scid xenograft model reconstituted
with human PBMC. Results: AFM11 mediates highly potent target tumor
cell lysis in cytotoxicity assays: EC 50 values are low to sub-picomolar range
in a panel of CD19 � cell lines and primary B-CLL tumor cells. The cytotoxic
activity of tetravalent AFM11 is superior to that of alternative bivalent
antibody formats possessing only a single binding site for both CD19 and
CD3. High affinity binding of AFM11 to CD19, and more so to CD3 (low to
sub-nanomolar Kd), is essential for efficacious T cell recruitment. The high
affinity bivalent binding of AFM11 to CD3 does not trigger T cell activation
in the absence of CD19 � target cells in functional in vitro assays. AFM11
activates T cells only in the presence of its targets and mediates lysis while
sparing antigen-negative bystanders. AFM11 induces down-modulation of
the CD3/TCR complex in the absence of target cells and at high concentrations.
Also, AFM11-treated T cells can be re-engaged for target cell lysis.
These features of AFM11-induced T cell activation may contribute additional
safety with no compromise of efficacy. Finally, AFM11 demonstrates
a robust dose-dependent inhibition of subcutaneous Raji tumors in mice.
Conclusions: AFM11 is a novel highly efficacious drug candidate for the
treatment of B cell malignancies with an advantageous safety profile.
8058 General Poster Session (Board #33G), Mon, 1:15 PM-5:15 PM
Hodgkin’s disease and HIV infection (HD-HIV): Prognostic factors in 596
patients (pts) within the group of European Cooperation on AIDS and
Tumors (GECAT). Presenting Author: Michele Spina, National Cancer
Institute, Aviano, Italy
Background: Hodgkin’s disease (HD) is the most common non-AIDS
defining tumour diagnosed in HIV setting. The introduction of highly active
antiretroviral therapy (HAART) has opened a new prospective in the
treatment of pts with HD-HIV as the better control of the underlying HIV
infection allows the use of more aggressive chemotherapy regimens,
including high dose chemotherapy. However, up to now prognostic factors
on overall survival (OS) or time to treatment failure (TTF) have not yet been
identified. Methods: In order to identify prognostic factors, we analyzed data
on 596 pts with HD-HIV diagnosed and treated in 90 different Institution of
6 European countries from October 1983 to March 2010. All factors were
analyzed for OS and TTF. Results: 86% of pts were male and the median
CD4 cell count was 224/dl (range 3-1274); 52% of pts had mixed
cellularity subtype, stages III-IV were diagnosed in 72% of cases and 55%
of pts had extranodal involvement (bone marrow 35%, spleen 21%, liver
14%). The table summarizes the results of multivariate analysis.
Conclusions: We identified a new “European Score” for HD-HIV able to
predict different outcomes in these patients. This score should be considered
for future prospective studies.
Factors Overall survival Time to treatment failure
IPS < 2 1 1
IPS > 2 2.33 (1.61-3.39) p�0.0001 1.57 (1.09-2.26) p�0.02
CD4 > 200 1 1
CD4 < 200 1.63 (1.16-2.29) p�0.005 1.43 (1.02-2.01) p�0.04
European Score
0 1 1
1 2.06 (1.40 - 3.02) 1.64 (1.17 - 2.30)
2 3.08 (2.13 - 4.45) p�0.001 2.31 (1.66 - 3.20) p�0.001
8060 General Poster Session (Board #34A), Mon, 1:15 PM-5:15 PM
Characteristics and outcomes of extranodal NK/t-cell lymphoma (ENKL): A
North American (NA) multi-institutional experience. Presenting Author:
Lauren Shizue Maeda, Stanford University Medical Center, Stanford, CA
Background: ENKL is a rare and aggressive subtype of peripheral T-cell
lymphoma. Due to its geographic predilection there is a paucity of data on
clinical experiences from non-Asian countries. The purpose of this study
was to analyze characteristics and outcomes of patients (pts) with ENKL
identified from major academic centers in NA. Methods: Pts with newly
diagnosed CD56� ENKL were retrospectively identified. Analyses included
disease characteristics, ethnicity, therapy, and outcomes. Results: 115 pts
(63.5% Caucasian, 20% Asian, 16.5% other) were identified across 10
centers diagnosed between 5/1990-5/2011 (Era 1: pre-2000, n�16; Era
2: 2000-2005, n�45; Era 3: post-2005, n�54). Median age was 52 years
(19-88). 75 (65%) had stage I/II disease and were treated with combined
modality therapy (CMT) n�48, chemotherapy (CT) n�14 or radiotherapy
(RT) n�14. 40 pts had stage III/IV disease and were treated with CT
(n�23), CMT (n�12) or RT (n�5). CT regimens used alone or in CMT were
either anthracycline-based (n�68) or other (n�29). 63% of stage I/II pts
and 40% with stage III/IV achieved complete remission (CR). 30 pts
underwent a stem cell transplant (SCT); 14 in first CR and 16 at
progression/relapse (autologous, n�21; allogeneic, n�9). Pts with stage
I/II disease had a better progression-free survival (PFS) and overall survival
(OS) compared with stage III/IV (12 vs 5.2 months (p�0.003) and 41.5 vs
8.9 months (p�0.0001), respectively). For all stages, treatment with CMT
compared with CT or RT alone was also associated with better PFS and OS,
18.0 vs 3.9 months (p�0.0001), and 41.5 vs 10.2 months (p�0.002)
respectively. Non-anthracycline-based regimens were associated with better
PFS (p�0.001) and OS (p�0.045). No survival differences were seen
between Asian and non-Asian pts. Conclusions: This series represents one
of the largest experiences of ENKL in NA. Our data are consistent with
Asian studies in: 1) majority of pts present with early stage disease; 2)
overall poor outcome; 3) superiority of CMT and non-anthracycline regimens.
Advances in understanding biology and international collaborative
efforts are required to improve outcome in this rare entity.
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