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

8077 General Poster Session (Board #36B), Mon, 1:15 PM-5:15 PM
Dual-point FDG-PET: A novel scanning technique in Hodgkin lymphoma
with bulky disease. Presenting Author: Andrea Gallamini, Hematology
Department, S. Croce General Hospital, Cuneo, Italy
Background: Interim 18F-FDG-PET (iPET) is the most important prognosticator
in advanced-stage ABVD-treated Hodgkin Lymphoma (HL), but in early
stage w/ or w/o bulky lesion a low PPV of iPET was reported. Dual-point PET
scan (2P-PET) has been used to discriminate unspecific inflammatory from
neoplastic FDG uptake. At the Tx end, with a single FDG-avid mass (SFAM),
the specificity of PET in Tx response evaluation was sub-optimal. We report
here preliminary results from a cohort of HL patients (p) presenting with
bulky lesions, scanned with 2P-PET with the aim to increase specificity and
PPV. Methods: From 12.2008 till 01.2012 24 HL bulky p from Italian,
French and Polish centers underwent 2P-PET at baseline (2P-PET-0), after
2 ABVD (2P-PET-2) and at Tx end (2P-PET-end). 2P-PET scanning
technique consisted in 2 consecutive image acquisitions �60’ (EaS) and
�120’(LaS) after single, standard-dose FDG injection. Tx was ABVD (x4 or
x6) � consolidation RxT. No Tx change was done based on iPET results.
Scans were reviewed by 2 expert readers in a consensus session. Standardized-Uptake
Value (SUV) MAX was calculated both in EaS and LaS using
Volume of Interest Regions (VOIs) in sites of residual FDG uptake already
recorded in PET-0. �SUVMAX and FDG retention index (RI) were calculated
from SUVs in the same VOIs of both scans. Results: In 24 p (1 stage I,12 II,
4 III, 7 IV), 34 2P-PET were done.10 p underwent 2P-PET-0: in 10/10
SUVMAX increased from EaS to LaS (�SUVMAX 1-4.3). 15 p had a
2P-PET-2: 12 with a mean-follow-up of 18.36 months were evaluable, 3
too short ( �1, �5, �6 months). 7/12 p showed a RI reduction of 55%
(200-14): all are in continuous CR (CCR). 5/12 p. showed a 20% (11-26)
RI increase: all progressed �1 to�9 months after Tx end. Overall 3/12
cases (1 false �, 2 false- with a Deauville score 4 and 2,3 respectively)
were correctly classified after 2P-PET. 9 p with a SFAM had a 2P-PET-end:
in the 5/9 with an increased RI of 23% (9-43) a biopsy proved HL relapse.
In 4/9 a reduced RI of -29% (9-45) was found: in 2 biopsy disclosed
presence of residual thymic along with inflammatory tissue and 2 were in
CCR �2 to�8 after Tx end. Conclusions: DSUV Max increased at baseline
and in all relapsing patients, and decreased in patients in CCR. The PPV
and a PNV of 2P-PET were 100%.
8080 General Poster Session (Board #36E), Mon, 1:15 PM-5:15 PM
The incorporation of rituximab (R) and liposomal doxorubicin (LD) into
CODOX-m/IVAC for untreated Burkitt lymphoma (BL): Final results of a
prospective multicenter phase II study. Presenting Author: Andrew M.
Evens, The University of Massachusetts Medical School, Worcester, MA
Background: Two-year survival rates remain �65-70% for adult BL.
Further, there is a paucity of data examining the addition of R with
CODOX-M/IVAC. Methods: 25 patients (pts) with classic BL enrolled onto
this phase II study (3/07-4/11). Pts were classified as low risk (LR) or high
risk (HR); LR received 3 CODOX-M, while HR had 4 alternating CODOX-M/
IVAC (Mead et al, Blood 2008). LD (40 mg/m2 ) was used in lieu of
doxorubicin, while intravenous R (500 mg/m2 ) was given days 0 � 8of
CODOX-M and days 0 � 6 of IVAC cycles. Ejection fraction (EF) was
assessed at baseline, s/p 2 cycles and completion. Results: Median age was
44 years (yrs) (23-70). There were 20 HR and 5 LR pts; 3 HR and 1 LR pt
were HIV�. 15% of HR pts had � CNS disease. In addition, 35% of HR pts
had bulk �10 cm and 40% had bone marrow involvement. 24/25 pts were
evaluable for toxicity and response. Therapy was completed at a median of
13 weeks (11-20) for HR pts and 10 weeks for LR (9-12). Myelosuppression
(62% grade 4 thrombocytopenia, 4% grade 4 anemia) and mucositis
(33% grade 3, 13% grade 4) appeared comparable with prior CODOX-M/
IVAC data. Other grade 3 toxicities were infection (38%), neutropenic fever
(29%), transaminitis (33%), diarrhea (8%), creatinine (8%), seizure (4%),
vomiting (4%). Notably, there was no grade 3 or 4 neuropathy. Two grade 2
and three grade 3 cardiac events occurred (all depressed EF, no clinical
CHF). Two of the three grade 3 cardiac events occurred in pts age �65 yrs.
Among all pts, the median change in EF at baseline vs study end was -2%
(-22% to �11%). The overall response rate (modified Cheson with
FDG-PET) after 2 cycles was 100% with a 67% complete remission rate. At
a median follow-up of 2.3 yrs, 2-year PFS and OS rates for all pts were 86%
and 86%, respectively (LR 2-yr PFS and OS: both 100%; HR 2-yr PFS and
OS: both 82%). Furthermore, 2-yr PFS and OS for HR, HIV-negative BL
were 91% and 91%, respectively (disease-specific survival: 100%).
Conclusions: The integration of R and LD into CODOX-M/IVAC for adult BL
is feasible and associated with similar tolerability compared with prior
reports. Moreover, this regimen was associated with excellent survival
rates, especially for HIV-negative BL.
Lymphoma and Plasma Cell Disorders
529s
8078 General Poster Session (Board #36C), Mon, 1:15 PM-5:15 PM
Association of tumor-associated macrophages of M2 subtype with outcome
in follicular lymphoma. Presenting Author: Clarinda Wei Ling Chua,
National Cancer Centre Singapore, Singapore, Singapore
Background: Current methods used to prognosticate patients with follicular
lymphoma (FL) include the Follicular Lymphoma International Prognostic
Index (FLIPI) and tumor grade. However, they do not provide information on
the biological and molecular features of FL. Recent data suggest that high
tumor-associated macrophages (TAM) content may be an adverse prognostic
factor in FL. However, TAM consists of two main subtypes, M1 and M2,
with the former related to pro-inflammatory properties while the latter,
anti-inflammatory functions. Currently, the prognostic impact of each
individual subtype has not been elucidated and this may be more important
than looking at TAM alone. Methods: Tumor specimens of 98 patients with
FL diagnosed between 2005 and 2009 were investigated using immunohistochemistry
and fluorescence in-situ hybridization (FISH) using breakapart
FISH probes targeting BCL2, BCL6, MYC and IgH genes. Tumor
specimens expressing a higher proportion of CD68�/CD163- in one high
power field were defined as M1 subtype and those that expressed a greater
proportion of CD68�/CD163� were denoted as M2 subtype. Results:
Amongst the 98 patients, 60 (61%) were of the M2 subtype, 59%
presented with advanced disease, 47% were grade 3 and the median age
was 59 years (21 – 88 years). Baseline characteristics including grade,
stage and recurrent translocations did not significantly differ between the
M1 and M2 groups. Similarly, there was also no difference in terms of
treatment received (both Rituximab and chemotherapy) between the two
groups. Despite these similarities, with a median follow-up of 3.2 years, the
3-year overall survival (OS) was significantly different (M1, 100% vs M2,
85%; p � 0.01). All 11 patients who died were of the M2 subtype
(p�0.009). Conclusions: Our findings show that despite similar patient
characteristics and treatment, there was, however, a statistically significant
difference in OS, with the M2 subtype demonstrating an inferior outcome.
The M2 TAM subtype rather than TAM alone may be a more important
prognostic marker in FL, which could possibly be explained by its known
biological anti-inflammatory function.
8081 General Poster Session (Board #36F), Mon, 1:15 PM-5:15 PM
Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma
patients refractory to prior rituximab. Presenting Author: Jennifer L. Wayne,
Mentrik Biotech, LLC, Dallas, TX
Background: Ocaratzumab, previously known as AME-133v, is a humanized
next-generation anti-CD20 monoclonal antibody. It has been optimized
with a 13 to 20-fold increase in binding affinity to CD20 and improved
binding to the low-affinity (F/F and F/V) polymorphisms of Fc�RIIIa (CD16),
which are thought to predict lower response rates and shorter duration of
responses to rituximab. Methods: In a phase I dose escalation study in
relapsed follicular lymphoma (FL) patients, ocaratuzumab was welltolerated
at doses up to 375 mg/m2 (Forero-Torres et al. CCR 2012). In a
follow-on phase II trial, 44 patients with relapsed FL following prior
rituximab and the low-affinity Fc�RIIIa polymorphism (F-carriers) received
375 mg/m2 of ocaratuzumab weekly for 4 doses. In this study, overall
response rate (ORR) was 36% and median progression free survival (PFS)
was 91 weeks (Ganjoo et al. Haematologica 2011). Results: Amongst the
56 patients receiving 100 and 375 mg/m2 of ocaratuzumab, 8 patients had
a previous time to progression of � 180 days following their last rituximab
treatment. These patients had a median of 2 prior rituximab treatments,
(range 1-6 treatments), and median PFS following last treatment of 159
days. Five of the 8 patients showed a longer PFS after ocaratuzumab
administration, compared with last rituximab treatment. All 5 patients
expressed the homozygous low-affinity genotype of Fc�RIIIa (F/F). At the
time of study closure, 3 of the patients were still in remission (indicated by
* in the table). Conclusions: This retrospective analysis suggests that
ocaratuzumab may be non-cross-resistant to rituximab in patients with the
low-affinity Fc�RIIIa polymorphism. Prolonged PFS in selected patients
following ocaratuzumab suggests that the increased binding affinity to
CD16 and improved antibody-dependent cell-mediated cytotoxicity (ADCC)
of this antibody is clinically relevant. As a single agent, ocaratuzumab may
provide prolonged clinical benefit in relapsed FL patients and a clinical trial
comparing ocaratuzumab to rituximab is in preparation.
No. of prior RTX treatments PFS after RTX (days) PFS after ocaratuzumab (days)
1 172 826*
2 159 636
1 97 434*
2 163 357*
3 103 257
6 180 168
2 116 119
2 176 91
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