To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab ((131)I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.
From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response > or = 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of (131)I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.
Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors < or = 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.
(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.
"Rituximab is a chimeric IgG1 kappa anti-CD20 antibody that mediates complement- and antibody-dependent cytotoxicity in vitro. In fact, the introduction of rituximab has truly revolutionized the management of patients with B-cell NHL . In addition to serving as a single agent as standard therapy for relapsed or refractory indolent NHL, rituximab has also been used in combination with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) in treatment of both indolent and aggressive NHLs. "
[Show abstract][Hide abstract] ABSTRACT: Nuclear medicine imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have played a prominent role in lymphoma management. PET with [(18)F]Fluoro-2-deoxy-D-glucose (FDG) is the most commonly used tool for lymphoma imaging. However, FDG-PET has several limitations that give the false positive or false negative diagnosis of lymphoma. Therefore, development of new radiotracers with higher sensitivity, specificity, and different uptake mechanism is in great demand in the management of lymphoma. This paper reviews non-FDG radiopharmaceuticals that have been applied for PET and SPECT imaging in patients with different types of lymphoma, with attention to diagnosis, staging, therapy response assessment, and surveillance for disease relapse. In addition, we introduce three radiolabeled anti-CD20 antibodies for radioimmunotherapy, which is another important arm for lymphoma treatment and management. Finally, the relatively promising radiotracers that are currently under preclinical development are also discussed in this paper.
"To our knowledge, safety data from registration trials of B have not been pooled in a separate publication and can only be extrapolated from the official product insert . A number of adverse reaction to the infusion were reported, including fever, chills, sweating, hypotension, nausea, bronchospasm     . All these events were transient and manageable. "
[Show abstract][Hide abstract] ABSTRACT: During the past decades, several radio-labelled monoclonal antibodies (mAb) have been tested in preclinical and clinical settings for radioimmunotherapy (RIT) of non-Hodgkin's Lymphomas (NHL). The only compounds that have been registered for RIT of relapsed/refractory NHL are 131 I-tositumomab (Bexxar ®) and 90 Y-ibritumomab-tiuxetan (Zevalin ®), both directed against CD20, indicating the favorable immunological characteristics of such antigen expressed by B-cell surface. The presence of a high-energy β -emitting radioactive source offers the unique chance to enhance the therapeutic effect of the antibody itself. Indeed, the proposed ―cross-fire effect‖ seems to overcome some of the mechanisms underlying resistance to mAb, allowing for killing neighboring cancer cells not expressing the CD20 antigen. The present chapter will summarize the clinical results of both Zevalin ® and Bexxar ® in the treatment of relapsed/refractory B-cell NHL. Efficacy in first line and consolidation therapy will be also discussed, as well as the inclusion of RIT in myeloablative chemo-regimens.
Rituximab: Pharmacology, Clinical Uses and Health Effects, Edited by Gerond V. Lake-Bakaar, 01/2013: chapter Rituximab-Like Radiolabelled Antibodies for the Treatment of Non-Hodgkin's Lymphomas: pages 103-123; Nova Science Publishers., ISBN: 978-1-62257-533-6
"Ibritumomab tiuxetan (Zevalin) is a CD20 mAb coupled with the radioactive isotope yttrium-90 or indium-111. I-131 Tositumumab (Bexxar) is a iodine-131-labeled CD20 mAb, based on the mouse CD20 mAb B1 and is used to treat follicular lymphoma (FL) patients  . This review will focus on the mechanisms of action of unconjugated CD20 mAbs. "
[Show abstract][Hide abstract] ABSTRACT: Therapeutic monoclonal antibodies (mAbs) that target the CD20 antigen on B cells are successfully used in the clinic for the depletion of B cells to treat various forms of cancer and autoimmune diseases. The first CD20 mAb, approved by the FDA in 1998, was rituximab (RTX) and since then it has been widely used to treat more than one million patients thus far. The success of RTX has led to a general interest in the mechanism of action of CD20 mAbs. CD20 mAbs can induce tumor killing via various mechanisms, such as direct induction of apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent lysis (CDC). Although we now understand these mechanisms better, it is still unclear which of these mechanisms is the most important for in vivo RTX action. Not every patient respond to RTX treatment and eventually the overwhelming majority will experience a relapse. Therefore, there is an urgent need to improve the efficacy of CD20 mAbs. This review aims to summarize our current understanding on the mechanism of action of CD20 mAbs.
American Journal of Cancer Research 12/2012; 2(6):676-90. · 4.17 Impact Factor
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