News in Brief

The first monoclonal antibody for the treatment of cancer, rituximab, was approved 5 years ago and has had a remarkable impact on the treatment of non-Hodgkin's lymphomas. Additionally, it sparked a renewed interest in antibodies in general that has revitalized this field of research. Multiple antibodies for a variety of malignant and nonmalignant indications are being evaluated. Some are now approved for anticancer indications (rituximab, ibritumomab, trastuzumab, gemtuzumab, alemtuzumab) and others are completing the review process at US (FDA) and European (EMEA) regulatory agencies. The impact of antiCD20 antibodies, particularly rituximab and ibritumomab, is evident in the way treatment strategies and outcomes have changed for the lymphoma patient. Other unconjugated antibodies (including Hu1D10, epratuzumab and alemtuzumab) and conjugated antibodies (including radiolabeled tositumomab) are under evaluation.     

Epratuzumab in the therapy of oncological and immunological diseases

B cells play an important role in the pathogenesis of certain lymphomas and leukemias, as well as many autoimmune diseases. Antagonistic B-cell antibodies are thus gaining an increasing role in the management of these diseases. The first antibody target in this regard was CD20, with the development and introduction of rituximab in the management of B-cell malignancies, as well as rheumatoid arthritis. A second candidate target is CD22. The first antagonistic antibody to this B-cell marker, epratuzumab, appears to function, in contrast to CD20 antibodies, more by modulation of B cells rather than by their high depletion in circulation. Originally developed for the treatment of non-Hodgkin’s lymphoma, epratuzumab has now been found to be effective, with a very good safety profile, in two prototype autoimmune diseases: systemic lupus erythematosus and primary Sjögren’s syndrome. Recent studies have demonstrated the activity and safety of epratuzumab in non-Hodgkin’s lymphoma patients who have relapsed or are refractive to conventional therapy, including rituximab, and has also shown good activity in follicular and diffuse large B-cell lymphoma in combination with rituximab. As such, this new investigative antibody may have a significant market potential owing to the multitude of diseases and patients who may benefit from a CD22, B-cell antibody immunotherapy that is complementary to the known effects and role of CD20 antibodies, but can usually be administered within 1 h and depletes approximately 50% of circulating B cells.     

Radioimmunotherapy and stem-cell transplantation in the treatment of aggressive B-cell lymphoma

High-dose chemotherapy and autologous stem-cell transplantation (ASCT) have an established therapeutic role in the treatment of chemo-sensitive relapsed aggressive lymphoma, but has limited success in chemo-refractory disease or in heavily pretreated, multiple relapsed patients. Recurrent disease is the major cause of treatment failure in all patient subsets and the majority is not cured. Methods for better eradication of underlying lymphoma are needed to improve outcome. Radioimmunotherapy (RIT) combines radiation delivered by radio-isotopes with the targeting effect of monoclonal antibodies. Two radioimmunoconjugates are currently approved for relapsed/resistant low-grade or transformed lymphoma: iodine-131 tositumomab and yttrium-90 ibritumomab tiuxetan. These agents are also effective in aggressive lymphoma. Radio-labeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. Their major toxicity is myelosuppression, which is easily reversed by ASCT and they can target disease sites with almost no added toxicity to normal tissues. RIT has been used in escalated doses as the sole treatment prior to ASCT or in standard or escalated doses combined with standard high-dose chemotherapy regimens. RIT was also combined with reduced-intensity conditioning and allogeneic SCT. Preliminary results are promising and suggest improved disease control with no added toxicity; however randomized studies are needed to confirm these initial observations.     

Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell transplantation for malignant lymphoma

High-dose therapy followed by autologous hematopoietic stem-cell transplantation is the preferred therapy for relapsed chemotherapy-sensitive aggressive non-Hodgkin lymphoma, and may play a role in the treatment of high-risk first-remission aggressive lymphomas, mantle-cell lymphomas and relapsed follicular lymphomas. The primary cause of failure of this approach is disease recurrence despite initial responses. Traditional high-dose regimens have relied upon myeloablative combinations of chemotherapy with or without total body irradiation. In the Western world, over 90% of lymphomas are of B-cell origin, and the vast majority of those that come to transplant remain CD20-positive. The development of radioimmunotherapeutic approaches targeting this antigen allows for either dose escalation with stem-cell support, or the addition of targeted therapy to conditioning regimens either as a replacement for total body irradiation or in addition to myeloablative chemotherapy regimens. Results to date with yttrium-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) suggest that the addition of radioimmunoconjugate therapy to conventional conditioning regimens results in a toxicity profile similar to that seen with chemotherapy conditioning alone. Demonstration of improved disease control will ultimately require phase-III studies, though preliminary results are promising.     

EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with <Superscript>90</Superscript>Y-radiolabelled ibritumomab tiuxetan (Zevalin)

Background In January 2004, EMEA approved ⁹⁰Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin’s lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine. Purpose The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease.     

Zevalin and BEAM (Z‐BEAM) versus rituximab and BEAM (R‐BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma

Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high‐dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty‐five patients had rituximab and BEAM (R‐BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium‐90 labeled CD20 targeting antibody, prior to BEAM (Z‐BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5‐year overall survival (OS) in the R‐BEAM and Z‐BEAM groups was 55% and 71% (p = 0.288), and the 4‐year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z‐BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R‐BEAM. Copyright © 2015 John Wiley & Sons, Ltd.