Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ)

Zinzani, Pier Luigi; Tani, Monica; Pulsoni, Alessandro; Gobbi, Marco; Perotti, Alessio; Luca, Stefano De; Fabbri, Alberto; Zaccaria, Alfonso; Voso, Maria Teresa; Fattori, Pierpaolo; Guardigni, Luciano; Ronconi, Sonia; Cabras, Maria Giuseppina; Rigacci, Luigi; Renzo, Amalia De; Marchi, Enrica; Stefoni, Vittorio; Fina, Mariapaola; Pellegrini, Cinzia; Musuraca, Gerardo; Derenzini, Enrico; Pileri, Stefano; Fanti, Stefano; Piccaluga, Pier Paolo; Baccarani, Michele

doi:10.1016/s1470-2045(08)70039-1

Cited by 79 publications

(47 citation statements)

References 26 publications

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“…241 The NCCN Guidelines also include radioimmunotherapy and alkylating agent-based chemotherapy (cyclophosphamide or chlorambucil) with or without rituximab as alternative options for elderly or infirm patients. First-Line Consolidation or Extended Dosing: Chemotherapy Followed by Radioimmunotherapy: Firstline chemotherapy followed by radioimmunotherapy with either 131 I-tositumumab [242][243][244][245] or 90 Y-ibritumom-ab [246][247][248][249] has been evaluated in several phase II studies. In the SWOG S9911 trial, CHOP followed by 131 I-tositumomab resulted in an overall response rate of 91%, including a 69% complete remission rate in patients with previously untreated FL.…”

Section: Nccn Recommendations For Stage II (Bulky Disease) and Stage mentioning

confidence: 99%

Non-Hodgkin's Lymphomas

Zelenetz

Abramson

Advani

et al. 2011

J Natl Compr Canc Netw

164

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OverviewNon-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B-, T-, or natural killer (NK) lymphocytes. In the United States, B-cell lymphomas represent 80% to 85% of the cases, with 15% to 20% being Tcell lymphomas; NK lymphomas are rare. In 2010, an estimated 65,540 new cases of NHL were diagnosed and 20,210 patients died of the disease.1 NHL is the sixth leading site of new cancer diagnoses among men and women, accounting for 4% of new cancer cases and 4% of cancer-related deaths.

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Section: Nccn Recommendations For Stage II (Bulky Disease) and Stage mentioning

confidence: 99%

Non-Hodgkin's Lymphomas

Zelenetz

Abramson

Advani

et al. 2011

J Natl Compr Canc Netw

164

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“…Retrospective analyses have indicated that the use of 90 Y-ibritumomab tiuxetan does not compromise the efficacy or safety of subsequent therapy (4). 90 Y-ibritumomab tiuxetan consolidation therapy was initially investigated in phase 2 trials that have shown promising results in terms of conversion from PR to CR and progression-free survival (PFS) (10,11). Recently, results of the phase 3, randomized first-line indolent trial showed that in patients with advanced FL who achieved at least a PR to different induction therapies, consolidation therapy with a single dose of 90 Y-ibritumomab tiuxetan significantly prolonged PFS by 2 y, compared with no further treatment (12).…”

Section: Fol Licular Lymphoma (Fl) Is the Most Common Form Of Indolenmentioning

confidence: 99%

Dosimetry of ⁹⁰Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial

Delaloye¹,

Antonescu²,

Louton³

et al. 2009

J Nucl Med

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The objective of this analysis was to assess the radiation exposure associated with 90 Y-ibritumomab tiuxetan when used as consolidation therapy in adults with low or minimal tumor burden after first-line therapy of advanced follicular lymphoma (FL). Methods:The patients who were enrolled in the phase 3 firstline indolent trial were 18 y or older, with CD20 1 grade 1 or 2 stage III or IV FL, and a partial response, complete response, or unconfirmed complete response to first-line chemotherapy. The patients were allocated randomly to receive a single infusion of unlabeled rituximab 250 mg/m 2 on day 27 and consolidation on day 0 with a single dose of 90 Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after unlabeled rituximab, 250 mg/m 2 , or no further treatment. On day 27, a subset of patients received an injection of 185 MBq of 111 In-ibritumomab tiuxetan immediately after unlabeled rituximab, 250 mg/m 2 , for central dosimetry analysis. Correlations were assessed between organ radiation absorbed dose and toxicity, body weight, body mass index, and progression-free survival. Results: Central dosimetry evaluations were available from 57 of 70 patients. Median radiation absorbed doses were 100 cGy (range, 28-327 cGy) for the red marrow and 72 cGy (range, 46-106 cGy) for the whole body. Radiation absorbed doses did not differ significantly between patients who had a partial response or complete response to initial therapy. Progression-free survival correlated significantly with the whole-body (r 5 0.4401; P 5 0.0006) and bone marrow (r 5 0.2976; P 5 0.0246) radiation dose. Body weight was significantly negatively correlated with whole-body radiation dose (r 5 20.4971; P , 0.0001). Neither the whole-body radiation dose nor the bone marrow radiation dose correlated with hematologic toxicity. Conclusion: In patients with low or minimal residual tumor burden after first-line chemotherapy of advanced FL, wholebody and bone marrow exposure after 90 Y-ibritumomab tiuxetan consolidation showed a significant positive correlation with progression-free survival, whereas dosimetric data could not predict hematologic toxicity.

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“…2 Today, 2 radiolabeled anti-CD20 IgG antibodies, 90 Y-ibritumomab tiuxetan (Zevalin; Cell Therapeutics, Seattle, WA; Bayer Schering Healthcare, Berlin, Germany) and 131 Itositumomab (Bexxar; GlaxoSmithKline, Philadelphia, PA), are approved for treatment of patients with follicular and transformed non-Hodgkin lymphoma (NHL) who failed or relapsed from prior therapies, including rituximab and standard chemotherapy. 3,4 Although results from ongoing clinical studies support the use of such radioimmunoconjugates in various front-line and salvage treatment settings, [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] important issues remain regarding how these agents are administered, yet also suggest some potential new treatment paradigms. 20 …”

Section: Introductionmentioning

confidence: 99%

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

Sharkey

Press

Goldenberg

2009

Blood

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Antibody-based therapies, both unconjugated antibodies and radioimmunotherapy, have had a significant impact on the treatment of non-Hodgkin lymphoma. Single-agent rituximab is an effective therapy, but it is being increasingly used with combination chemotherapy to improve the objective response and its duration. The approved anti-CD20 radioimmunoconjugates ( 90 Y-ibritumomab tiuxetan or 131 I-tositumomab) have had encouraging results, with trials now seeking to incorporate a radioimmunoconjugate in various settings. However, new preclinical data raise important questions concerning current radioimmunoconjugate treatment regimens and ways to improve them. In radioconjugate therapy, nearly 900 mg of the unlabeled anti-CD20 IgG antibody is predosed to the patient before the anti-CD20 antibody conjugated to either 90 Y or 131 I is given. Combining an unconjugated anti-CD20 antibody therapy with a radioimmunoconjugate binding to a noncompeting antigen might improve responses by allowing optimal uptake of each agent. Preclinical models have indicated that careful consideration should be given to predosing when using competing antibodies, but that consolidation anti-CD20 therapy enhances the efficacy of radioimmunoconjugate therapy. New technologies, such as pretargeted radioimmunotherapy, also hold promise by reducing toxicity without sacrificing efficacy, and consideration should be given to fractionating or giving multiple radioimmunoconjugate treatments. This perspective discusses how these issues could affect current and future clinical trials. IntroductionTargeting cancer with radiolabeled antibodies, first demonstrated by diagnostic imaging 1 and subsequently developed into radioimmunotherapy (RAIT), has remained an active field of study for more than 30 years. 2 Today, 2 radiolabeled anti-CD20 IgG antibodies, 90 Y-ibritumomab tiuxetan (Zevalin; Cell Therapeutics, Seattle, WA; Bayer Schering Healthcare, Berlin, Germany) and 131 Itositumomab (Bexxar; GlaxoSmithKline, Philadelphia, PA), are approved for treatment of patients with follicular and transformed non-Hodgkin lymphoma (NHL) who failed or relapsed from prior therapies, including rituximab and standard chemotherapy. 3,4 Although results from ongoing clinical studies support the use of such radioimmunoconjugates in various front-line and salvage treatment settings, 5-19 important issues remain regarding how these agents are administered, yet also suggest some potential new treatment paradigms. 20 Current radioimmunoconjugate therapy of NHL: development and practiceWe believe a major issue is the role and dose of unconjugated anti-CD20 antibody given prior to the radioimmunoconjugate in both products. In the United States, patients first receive 250 mg/m 2 of rituximab a few hours before receiving 111 In-ibritumomab; 2 to 3 days later, an imaging study then establishes a "normal" biodistribution pattern, and then another 250 mg/m 2 predose of rituximab is given before 90 Y-ibritumomab within 1 week of the first dose. In Europe, the 111 In imaging study is n...

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Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ)

Cited by 79 publications

References 26 publications

Non-Hodgkin's Lymphomas

Non-Hodgkin's Lymphomas

Dosimetry of ⁹⁰Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

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Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ)

Cited by 79 publications

References 26 publications

Non-Hodgkin's Lymphomas

Non-Hodgkin's Lymphomas

Dosimetry of 90Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

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Product

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Dosimetry of ⁹⁰Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial