Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive after Rituximab
ABSTRACT 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.
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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
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ABSTRACT: Leukaemia is the single most common childhood malignancy. With modern treatment regimens, survival in acute lymphoblastic leukaemia (ALL) approaches 90%. Only about 70% of children with acute myeloid leukaemia (AML) achieve long term survival. Patients who relapse have a dismal prognosis. Novel therapeutic approaches are needed to improve treatment outcomes in newly-diagnosed patients with a poor prognosis and for patients with relapsed/refractory disease that have limited treatment options. One promising approach in treating haematological malignancies has been the use of monoclonal antibodies to target cell surface antigens expressed on malignant cells. Most success with monoclonal antibody therapy in the treatment of haematological malignancies has come in the setting of adult B-cell non-Hodgkin lymphoma with the addition of the anti-CD20 monoclonal antibody rituximab to standard treatment regimens. In order to further advance treatment of haematological malignancies, novel monoclonal antibodies continue to be developed that target a variety of cell surface antigens. Several antibodies continue to be investigated in childhood leukaemias. This review will discuss the development of monoclonal antibodies that target a variety of cell surface antigens for the treatment of childhood ALL and the use of the anti-CD33 antibody gemtuzumab ozogamicin in the treatment of childhood AML.British Journal of Haematology 08/2012; 159(1):3-17. DOI:10.1111/bjh.12002
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ABSTRACT: The activity of radio-immuno conjugate in Non-Hodgkin Lymphoma (NHL) has resulted in FDA approval of two antibodies, Y(90) Ibritumomab tiuxetan and I(131) tositumomab. Both these agents target CD20, a receptor widely expressed in B-Cell NHL. These immunoconjugates deliver their radioactive payload to the malignant clone in the bone marrow and lymph node. Their use has been associated with modest improvement in survival end points among several lymphoma histologies. The promising effect on disease control as well as their efficacy in disease relapse is encouraging in low grade lymphoma. Radioimmunotherapy (RIT) is increasingly being explored in the setting of consolidation as well as conditioning regimens prior to stem cell transplantation. Here, we summarize the clinical use, complications and future applications of RIT in NHL.01/2012; 2(2):86-97.