Current status and future perspectives for yttrium-90 (90Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin's lymphoma

Abstract

Haematopoietic SCT is currently considered a therapeutic option mainly in relapsed or refractory non-Hodgkin's lymphoma (NHL) owing to high post-transplantation relapse rates and significant toxicity of conventional myeloablative conditioning for allogeneic SCT. Radiolabelled immunotherapy combines the benefits of monoclonal antibody targeting with therapeutic doses of radiation, and is a promising advance in the treatment of malignant lymphomas. It is now under investigation as a component of conditioning prior to SCT, with the aim of improving outcomes following SCT without increasing the toxicity of high-dose chemotherapy pretransplant conditioning. An expert panel met at a European workshop in November 2006 to review the latest data on radiolabelled immunotherapy in the transplant setting, and its potential future directions, with a focus on 90 Y-ibritumomab tiuxetan. They reviewed data on the combination of standard/high/escalating dose 90 Yibritumomab tiuxetan with high-dose chemotherapy, and high/escalating dose 90 Y-ibritumomab tiuxetan as the sole myeloablative agent, prior to autologous SCT, and also 90 Y-ibritumomab tiuxetan as a component of reduced intensity conditioning prior to allogeneic SCT. The preliminary data are highly promising in terms of conditioning tolerability and patient outcomes following transplant; further phase II studies are now needed to consolidate these data and to investigate specific patient populations and NHL subtypes.

Second-line treatment paradigms for diffuse large B-cell lymphomas

“…More phase 2 and subsequent phase 3 studies are needed to evaluate the role of 90 Y-ibritumomab tiuxetan in combination with HDT (eg, Z-BEAM vs BEAM) or alone before ASCT. These studies should investigate different patient subgroups and analyze outcomes according to histology [23,24].…”

“…Several independent studies in the transplant setting showed that 90 Y-ibritumomab tiuxetan has a promising role in conditioning regimens, not only as an adjunct to standard chemotherapy (immunotherapyenhanced conditioning) but also as the sole conditioning agent, extending the option of transplantation to a wider range of patients [21][22][23][24][25]. In ASCT, the use of 90 Y-ibritumomab tiuxetan combined with HDT has no effect on the speed of engraftment and has a toxicity profi le similar to that of conventional conditioning regimens [22,26].…”

Mantle cell lymphoma: Are current therapies changing the course of disease?

“…The European MCL Network trials are now comparing classical total-body irradiation (TBI) at 12 Gy plus cyclophosphamide at 120 mg/kg (CTX) with TAM (TBI, 10 Gy; cytarabine, 6 g/m 2 ; and melphalan, 140 mg/m 2 ) [23]. The high radiosensitivity of MCL, however, is now exploited in the form of radioimmunotherapy targeting CD20, with two agents presently available-yttrium 90 ( 90 Y)-ibritumomab tiuxetan (Zevalin; Cell Therapeutics, Inc., Seattle, WA) and iodine 131 ( 131 I)-tositumomab (Bexxar; GlaxoSmithKline, Philadelphia, PA, and Biogen Idec, San Diego, CA)-both with documented effi cacy in MCL (reviewed by Gisselbrecht et al [34] and Park and Press [35]). Followed by stem cell support, radioimmunotherapy as part of the preparatory regimen appears to be an effective and well-tolerated alternative to TBI [36].…”

Radioimmunotherapy for Stem Cell Transplantation in Non-Hodgkin’s Lymphoma: In Pursuit of a Complete Response

“…This is especially pertinent because the majority of patients with relapsed or refractory B-cell NHL are Ͼ60 years old, and yet are often denied potentially curative HDC and/or TBI and ASCT because of the risk for excessive treatmentrelated morbidity and mortality [20,21]. In contrast to TBI, and by virtue of its targeted activity, RIT (conventional and high dose) can be used in elderly patients with comorbidities undergoing SCT, making it appropriate as a pretransplant regimen for a wider patient population [19]; as such, a dramatic decrease in TBI-containing regimens has been observed in data from the European Group for Blood and Marrow Transplantation registry since 2000 [22,23]. In two studies, 90 Yibritumomab tiuxetan was used to treat patients with NHL who were not eligible for HDC-and/or TBI-containing therapies prior to ASCT.…”