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Annals of Oncology
Reed-Sternberg cells. This redirected immune response leads to potent tumor cell
killing. RECRUIT TandAbs are tetravalent and bispecific, and address key
deficiencies of monoclonal antibodies such as (i) differential binding to V/F allotypes
of CD16A receptor and (ii) non-selective binding to activating CD16A and
non-signalling CD16B receptors. Furthermore, RECRUIT-TandAbs have significant
advantages over other antibody fragment technologies such as (i) bivalent binding to
the targets and, (ii) longer half-life.
AFM13 binds with high affinity to both CD30 and CD16A and is able to rapidly
induce lysis of CD30+ cells at picomolar concentrations in the presence of PBMCs.
Intensive in vitro characterization demonstrated that AFM13 is specific for the
CD16A receptor, which becomes activated only in the presence of tumor cells: there
is no systemic activation of NK-cells in the absence of target cells. A robust GMP
production process in mammalian cells and a lyophilized formulation with excellent
stability have been established. Toxicology testing in Cynomolgus monkeys did not
reveal any toxicity. Currently, AFM13 is being investigated in a single arm phase I
dose escalation trial for patients with relapsed and/or refractory Hodgkin Lymphoma
(HL). Patients receive a single cycle of 4 weekly doses, which are escalated in cohorts
of 3 patients at the dose levels of 0.01, 0.04, 0.15, 0.5, 1.5, 4.5 and 7.0 mg/kg. Study
objectives are the assessment of safety and tolerability, PK, immunogenicity,
antitumor activity, as well as the determination of the maximum tolerated dose
(MTD) or the optimal biological dose (OBD). The safety of the MTD or OBD will
be confirmed in further patients receiving 2 cycles of AFM13.
AM13 was shown to be safe and well tolerated by highly pre-treated Hodgkin
Lymphoma patients in weekly doses of up to 7.0 mg/kg. Adverse events were
generally mild, with the most frequent drug-related event being fever. An objective
response was achieved on the dose level 1.5mg/kg. Nine cases of stable disease/minor
response were also observed. In ex vivo assays AFM13 restored impaired cytotoxic
activity of NK cells from HL patients. Preclinical and interim clinical data will be
presented, showing that AFM13 may become a safe and effective targeted therapy for
CD30 positive malignancies.
Disclosures: E. Zhukovsky: The author is the employee of Affimed Therapeutics and
the member of the Management Board, M. Ravic: A consultant to Affimed
Therapeutics and a Chief Medical Officer, M. Topp: Consultant to Affimed, S.
Knackmuss: The coauthor is an employee of the company. U. Reusch: The coauthor
is an employee of the company. E. Rajkovic: The coauthor is an employee of the
company. C. Hucke: The co-author is a former employee of Affimed Therapeutics
and currently is a clinical development consultantM. Little: The co-author is a
consultant to Affimed Therapeutics and owns the warrants of the company.
1073P CONSOLIDATION TREATMENT WITH Y90-IBRITUMOMAB
TIUXETAN AFTER R-CHOP INDUCTION IN HIGH-RISK
PATIENTS WITH FOLLICULAR LYMPHOMA (FL)
(GOTEL-FL1LC): A MULTICENTRIC, PROSPECTIVE STUDY
M. Provencio Pulla 1 , M.A. Cruz Mora 2 , J. Gomez Codina 3 , C. Quero 4 ,
M. Llanos 5 , F.R. Garcia Arroyo 6 , L. De La Cruz 7 , J. Guma 8 , J.R. Delgado 9 ,
A. Rueda 10
1 Medical Oncology, Hospital Universitario Puerta de Hierro Majadahond,
Majadahonda, SPAIN, 2 Medical Oncology, Hospital Virgen de la Salud, Toledo,
SPAIN, 3 Medical Oncology, Hospital Universitari i Polit, Valencia, SPAIN,
4 Radiotherapy, Hospital Universitario Virgen de la Victoria, Malaga, SPAIN,
5 Medical Oncology, Hospital Universitario de Canarias, Tenerife, SPAIN, 6 Medical
Oncology, Complejo Hospitalario de Pontevedra, Pontevedra, SPAIN, 7 Medical
Oncology, Hospital Universitario Virgen Macarena, Sevilla, SPAIN, 8 Medical
Oncology, Hospital Universitario San Juan de Reus, Reus, SPAIN, 9 Medical
Oncology, Hospital Universitario Virgen de las Nieves, Granada, SPAIN,
10 Medical Oncology, Hospital Costa del Sol, Marbella, SPAIN
Relapse is the main cause of therapeutic failure in FL, which makes it necessary to
investigate strategies that aim to eradicate minimal residual disease. This is why we
set out to evaluate the role of consolidation with Y90-Ibritumomab Tiuxetan (RIT)
in high-risk FL patients. As we possessed data making us suspect that prior
treatment with Rituximab could reduce the efficacy of RIT, we designed a study with
RIT after 4 cycles of CHOP-R and 2 CHOP, but without R.
Material and Patients: Between April 2008 and April 2010, 30 patients were
included in this trial: 17 male (56.7%) and 13 female (43.3%). Their median age was
54.8 (range, 34-76). 20 (69%) patients had ECOG 0. There were no delays or
reductions in RIT doses.
Results: The objective rate of clinical response was 92.1% (CR + CRi + PR), [CI 95%:
83-100%]. Of the 18 patients who presented with partial remission to the induction
treatment, 11 (61.1%) had complete CR or remission after the consolidation
treatment. There was only one exitus, due to H1N1 viral pneumonia. The most
important G 3/4 toxicity was hematological, with 46% thrombopenia and 56%
neutropenia. None of the patients in the trial died because of Lymphoma. With
median follow-up of 26 months (12-37), the means for disease-free survival or
overall survival were not reached.
Conclusion: The induction procedure with 4 CHOP-R + 2 CHOP prior to consolidation
with RIT gives good response rates and RIT improves CR. This combination is safe and
shows a high activity in both, induction and consolidation procedures.
Disclosure: All authors have declared no conflicts of interest.
1074P A RETROSPECTIVE SINGLE CENTRE ANALYSIS OF SAFETY,
TOXICITY AND EFFICACY OF RITUXIMAB (ORIGINAL) AND
ITS BIOSIMILAR IN DIFFUSE LARGE B-CELL LYMPHOMA
PATIENTS TREATED WITH CHEMO-IMMUNOTHERAPY
P.S. Roy 1 , M. Sengar 1 , H. Menon 1 , B. Bagal 1 , N. Khattry 1 , E. Shridhar 2 ,
S. Gujral 2 , S. Laskar 3 , V. Rangarajan, 4 , R. Nair 5
1 Medical Oncology, Tata Memorial Hospital, Mumbai, INDIA, 2 Pathology, Tata
Memorial Hospital, Mumbai, INDIA, 3 Radiation Oncology, Tata Memorial
Hospital, Mumbai, INDIA, 4 Radiology, Tata Memorial Hospital, Mumbai, INDIA,
5 Medical Oncology, Tata Memorial Hospital Centre, Mumbai, INDIA
Background: Rituximab with chemotherapy (CHOP regimen) has been the standard
of care for diffuse large B-cell lymphoma (DLBCL). Mabthera® is being used in India
since early 2000. Reditux®, a biosimilar molecule of Rituximab, was developed in
India & approved for use since March 2007. This retrospective audit aims to
compare the safety, toxicity and efficacy of Mabthera® with Reditux®.
Methods: Two hundred twenty-three patients aged ≥ 18 years who underwent
treatment from January 2004 to June 2010 were included. All patients received 4-8
cycles of R-CHOP. CT scan of chest & abdomen was done at baseline and within 4
weeks of completion of treatment. Grade 3-4 hematological and non-hematological
toxicities according to CTC version 3.0 were recorded. Response rates [complete
response (CR), partial response (PR)] in both groups were evaluated as per Cheson’s
criteria & compared by Chi-Square test. Overall survival (OS) and progression-free
survival (PFS) were estimated by Kaplan-Meier method & compared by two-sided
log rank test.
Results: One hundred one patients received Mabthera®, 72 received Reditux®. In 17
patients, the brand used was unknown and 33 patients received both. Baseline
characteristics such as, age, gender, performance status, stage of disease & revised IPI
score at presentation were similar in both groups. Median number of treatment cycle
received was 6 in each group. Overall response rate (CR + PR) was 88% (Mabthera®)
and 90% (Reditux®). OS at 5 years was 85% (Mabthera®) and 93% (Reditux®); P = 0.13.
PFS at 5 years was 76% (Mabthera®) and 84% (Reditux®); P = 0.44. At a median
follow-up of 35 months (18 to 58 months) treatment related death was seen in 3 in
Mabthera® and 2 in Reditux® group. Grade 3-4 febrile neutropenia was observed in 23%
(Mabthera®) & 20% (Reditux®); grade 3-4 oral mucositis and diarrhea was seen in 25%
(Mabthera®) & 10% (Reditux®). No difference in infusional reactions were observed.
Conclusion: Reditux® is as efficacious as Mabthera® in terms of response rates, OS &
PFS with comparable toxicity. However, randomized prospective trial is needed to
validate these results.
Disclosure: All authors have declared no conflicts of interest.
1075P DETECTION OF CAGA EXPRESSION IN GASTRIC
MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA—
BIOLOGIC SIGNIFICANCE AND CLINICAL IMPLICATION
S. Kuo 1 , L. Chen 2 , C. Lin 3 ,M.Wu 4 , P. Hsu 4 , Y. Tzeng 1 , H. Tsai 2 , H. Wang 4 ,
K. Yeh 1 , A. Cheng 1
1 Departments of Oncology, National Taiwan University Hospital, Taipei, TAIWAN,
2 National Institute of Cancer Research, National Health Research Institutes,
Tainan, TAIWAN, 3 Departments of Pathology, National Taiwan University
Hospital, Taipei, TAIWAN, 4 Departments of Internal Medicine, National Taiwan
University Hospital, Taipei, TAIWAN
Background: We recently reported that a direct contact of Helicobacter pylori (HP)
with B cells resulted in CagA translocation into the cells (Cancer Res
2010;70:5740-8). The translocated CagA further activates extracellular
signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK),
and up-regulates the expressions of Bcl-2 and Bcl-xL. In this study, we sought to
verify if CagA exists in the malignant B cells of gastric mucosa-associated lymphoid
tissue (MALT) lymphoma.
Methods: Expression of CagA protein, phospho-SHP-2, phospho-ERK,
phospho-p38MAPK, Bcl-2 and Bcl-xL in a series of 26 gastric MALT lymphoma was
determined by immunohistochemistry. Western blot analysis was done to confirm
immunohistochemical detection of CagA and biopsies from non-gastric MALT
lymphoma served as negative controls. The association of CagA expression and the
tumor response to HP-eradication (HPE) therapy was evaluated in 77 stage IE/IIE1
low-grade gastric MALT lymphoma patients.
Results: The expression of CagA was detected in 35 (45.5%) of 77 patients. CagA
expression was closely associated with the expression phospho-SHP-2 (P = .016),
phospho-ERK (P < .001), phospho-p38MAPK (P = 0.014), Bcl-2 (P = 0.009), and
Bcl-xL (P = 0.008). CagA expression was detected in 30 (69.8%) of 43 HP-dependent
cases, and in 5 (14.7%) of 34 HP-independent cases (P < 0.001). Furthermore,
patients with CagA expression responded to HPE more rapidly than those without
(median time to complete remission, 3.0 months versus 7.0 months, P = 0.032).
Conclusion: CagA protein can be translocated into malignant B cells of MALT
lymphoma. The expression of CagA in lymphoma cells appears to be biologically and
clinically significant.
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds403 | ix351