Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

Shimoni, Avichai; Zwas, S. Tzila; Oksman, Yakov; Hardan, Izhar; Shem‐Tov, Noga; Rand, Avital; Yerushalmi, Ronit; Avigdor, Abraham; Ben-Bassat, I; Nagler, Arnon

doi:10.1038/sj.bmt.1705919

Cited by 44 publications

(26 citation statements)

References 40 publications

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“…Shimoni et al also observed a high incidence of severe gastrointestinal GVHD in their study of RIT combined with RIC. 28 Whether this is influenced by the use of RIT in the conditioning remains unclear. However, our rates of acute grade 2-4 and extensive chronic GVHD are BLOOD, 9 SEPTEMBER 2010 ⅐ VOLUME 116, NUMBER 10 For personal use only.…”

Section: Discussionmentioning

confidence: 99%

“…23 In allogeneic HCT, so far only 1 small phase 1 or 2 study and 1 case report evaluated the combined approach of RIT with RIC. 28,29 Shimoni et al reported 12 patients with low-and high-grade NHL RIT using 90 Y-ibritumomab tiuxetan followed by RIC with fludarabine/busulphan/melphalan. 28 Fietz et al reported 2 additional patients combining 90 Y-ibritumomab tiuxetan with RIC using fludarabine/cyclophosphamide.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Shimoni et al reported 12 patients with low-and high-grade NHL RIT using 90 Y-ibritumomab tiuxetan followed by RIC with fludarabine/busulphan/melphalan. 28 Fietz et al reported 2 additional patients combining 90 Y-ibritumomab tiuxetan with RIC using fludarabine/cyclophosphamide. 29 Moderate toxicity of this approach was observed, with main toxicities related to RIC and allogeneic HCT but not attributable specifically to RIT.…”

Section: Discussionmentioning

confidence: 99%

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Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study

Bethge

Lange

Meisner

et al. 2010

Blood

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Forty patients were enrolled in this phase 2 study combining radioimmunotherapy (RIT) using yttrium-90-ibritumomab-tiuxetan (15 MBq [0.4 mCi]/kg) with reduced-intensity conditioning (RIC) using fludarabine (90 mg/m 2 ) and 2 Gy total body irradiation followed by allogeneic hematopoietic cell transplantation (HCT) from related (n ‫؍‬ 13) or unrelated (n ‫؍‬ 27) donors for the treatment of advanced non-Hodgkin lymphoma. Diagnoses were follicular lymphoma (n ‫؍‬ 17), chronic lymphocytic leukemia (n ‫؍‬ 13), mantle cell lymphoma (n ‫؍‬ 8), marginal zone lymphoma (n ‫؍‬ 1), and lymphoplasmacytic lymphoma (n ‫؍‬ 1). Median age was 55 years (range, 34-68 years). All patients were high risk with refractory disease or relapse after preceding autologous HCT. No additional toxicities attributable to RIT were observed. Engraftment was rapid and sustained. Incidences of acute graft-versus-host disease 2-4 and chronic graft-versus-host disease were 43% and 53%, respectively. Kaplan-Meierestimated nonrelapse mortality was 45% at 2 years. Twenty-two of 40 patients (55%) are alive, resulting in a KaplanMeier-estimated 2-year survival of 51% for all, 67% for follicular lymphoma, 49% for chronic lymphocytic leukemia, and 37% for mantle cell lymphoma patients. The combined use of RIT with RIC is feasible with acceptable toxicity, even in elderly and heavily pretreated patients. This study is registered at www.clinicaltrials.gov as #NCT00302757. (Blood. 2010;116(10): 1795-1802)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study

Bethge

Lange

Meisner

et al. 2010

Blood

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“…Eighty-three percent of patients achieved a CR or a PR, and, at a median follow-up of 21 months, the 2-year PFS rate was 33% and the 2-year response rate was relatively low (25%). Toxicity was similar to that observed with similar regimens not containing 90 Y-ibritumomab, once again indicating that adding RIT to chemotherapy does not increase toxicity [55]. The low incidence of relapse reported in this study will encourage further evaluation of 90 Y-ibritumomab tiuxetan RIC and alloSCT in refractory NHL.…”

Section: Does Rit Have a Role In Nonmyeloablative Conditioning In Allmentioning

confidence: 58%

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

et al. 2009

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High-dose chemotherapy (HDC) conditioning given in association with autologous stem cell transplantation (ASCT) or reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (alloSCT) are established treatment approaches for patients with chemotherapy-sensitive, relapsed, aggressive, or low-grade non-Hodgkin's lymphoma (NHL). These approaches have been shown to be the only curative option for patients with relapsed NHL. Despite data suggesting that prolonged event-free survival can be achieved with SCT combined with HDC, there are problems that may limit the utility of this approach for a broad patient population. For example, older patients, who make up the majority of the NHL population, may not be able to withstand the toxicities associated with this intensive regimen, and this therapy combination, especially when it includes the use of total-body irradiation, has been associated with a greater risk for secondary malignancies. Furthermore, relapse is the most common cause of treatment failure after HDC with ASCT and there is a poor success rate for those patients with either chemotherapy-refractory or heavily pretreated, multiple-relapsed disease. Consequently, there is an urgent need for other effective and well-tolerated approaches that will eradicate the residual disease that may persist before SCT, thus improving outcomes for patients with this life-threatening disease. In addition, approaches with better safety profiles would allow older patients to benefit from this therapeutic option. Because lymphomas are highly sensitive to radiation, radioimmunotherapy (RIT) has been used with great success in consolidation therapy and, as a result, there is great interest in exploring the use of RIT, either as a single agent or as augmentation of HDC, as part of a conditioning regimen for ASCT. The flexibility of including RIT as part of conditioning therapy also allows it to be combined with RIC to reduce the toxic effects of HDC. This treatment option replaces any concomitant loss of chemotherapy efficacy with a gain in RIT efficacy. The data so far suggest that the use of RIT in the au-

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“…Shimoni and colleagues 56,57 have also investigated 90 Yibritumomab tiuxetan as part of an RIC regimen using either fludarabine/melphalan or fludarabine/busulphan prior to allogeneic SCT in patients with chemorefractory aggressive NHL (Table 4). Patients were eligible for inclusion if they did not achieve a CR with prior chemotherapy (either as initial treatment or after relapse) and had active lymphoma by PET-CT scan, or if they had relapsed after a prior autologous SCT.…”

Section: The Role Of Radiolabelled Immunotherapy In Allogeneic Sctmentioning

confidence: 99%

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

Gisselbrecht

Bethge

Duarte

et al. 2007

Bone Marrow Transplant

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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.

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Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

Cited by 44 publications

References 40 publications

Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study

Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study

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

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

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