Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma

Ernst J. Postema, John M M Raemaekers, Wim J G Oyen, Otto C. Boerman, Caroline M P W Mandigers, David M. Goldenberg, Guus A M S Van Dongen, Frans H M Corstens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of 186Re-epratuzumab in patients with NHL. Experimental Design: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received 99mTc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with 186Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m2. Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m2; otherwise three additional patients were included on that dose level. Results: A total of 18 patients received a diagnostic dose of 99mTc-epratuzumab. Fifteen patients were actually treated with 186Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m2. During or after infusion of 186Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m2 dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m2, no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. Conclusions: 186Re-epratuzumab at a dose of 2.0 GBq/m2 is well tolerated without major toxicity. A single dose of 186Re-epratuzumab led to objective responses in 5 of 15 treated patients.

Original languageEnglish
JournalClinical Cancer Research
Volume9
Issue number10 II
Publication statusPublished - 1 Oct 2003

Cite this

Postema, E. J., Raemaekers, J. M. M., Oyen, W. J. G., Boerman, O. C., Mandigers, C. M. P. W., Goldenberg, D. M., ... Corstens, F. H. M. (2003). Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. Clinical Cancer Research, 9(10 II).
Postema, Ernst J. ; Raemaekers, John M M ; Oyen, Wim J G ; Boerman, Otto C. ; Mandigers, Caroline M P W ; Goldenberg, David M. ; Van Dongen, Guus A M S ; Corstens, Frans H M. / Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 10 II.
@article{1258acae11de4518840dbece882b51a1,
title = "Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma",
abstract = "Purpose: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of 186Re-epratuzumab in patients with NHL. Experimental Design: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received 99mTc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with 186Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m2. Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m2; otherwise three additional patients were included on that dose level. Results: A total of 18 patients received a diagnostic dose of 99mTc-epratuzumab. Fifteen patients were actually treated with 186Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m2. During or after infusion of 186Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m2 dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m2, no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. Conclusions: 186Re-epratuzumab at a dose of 2.0 GBq/m2 is well tolerated without major toxicity. A single dose of 186Re-epratuzumab led to objective responses in 5 of 15 treated patients.",
author = "Postema, {Ernst J.} and Raemaekers, {John M M} and Oyen, {Wim J G} and Boerman, {Otto C.} and Mandigers, {Caroline M P W} and Goldenberg, {David M.} and {Van Dongen}, {Guus A M S} and Corstens, {Frans H M}",
year = "2003",
month = "10",
day = "1",
language = "English",
volume = "9",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10 II",

}

Postema, EJ, Raemaekers, JMM, Oyen, WJG, Boerman, OC, Mandigers, CMPW, Goldenberg, DM, Van Dongen, GAMS & Corstens, FHM 2003, 'Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma' Clinical Cancer Research, vol. 9, no. 10 II.

Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. / Postema, Ernst J.; Raemaekers, John M M; Oyen, Wim J G; Boerman, Otto C.; Mandigers, Caroline M P W; Goldenberg, David M.; Van Dongen, Guus A M S; Corstens, Frans H M.

In: Clinical Cancer Research, Vol. 9, No. 10 II, 01.10.2003.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma

AU - Postema, Ernst J.

AU - Raemaekers, John M M

AU - Oyen, Wim J G

AU - Boerman, Otto C.

AU - Mandigers, Caroline M P W

AU - Goldenberg, David M.

AU - Van Dongen, Guus A M S

AU - Corstens, Frans H M

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Purpose: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of 186Re-epratuzumab in patients with NHL. Experimental Design: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received 99mTc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with 186Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m2. Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m2; otherwise three additional patients were included on that dose level. Results: A total of 18 patients received a diagnostic dose of 99mTc-epratuzumab. Fifteen patients were actually treated with 186Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m2. During or after infusion of 186Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m2 dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m2, no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. Conclusions: 186Re-epratuzumab at a dose of 2.0 GBq/m2 is well tolerated without major toxicity. A single dose of 186Re-epratuzumab led to objective responses in 5 of 15 treated patients.

AB - Purpose: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of 186Re-epratuzumab in patients with NHL. Experimental Design: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received 99mTc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with 186Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m2. Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m2; otherwise three additional patients were included on that dose level. Results: A total of 18 patients received a diagnostic dose of 99mTc-epratuzumab. Fifteen patients were actually treated with 186Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m2. During or after infusion of 186Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m2 dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m2, no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. Conclusions: 186Re-epratuzumab at a dose of 2.0 GBq/m2 is well tolerated without major toxicity. A single dose of 186Re-epratuzumab led to objective responses in 5 of 15 treated patients.

UR - http://www.scopus.com/inward/record.url?scp=0141568082&partnerID=8YFLogxK

M3 - Article

VL - 9

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10 II

ER -

Postema EJ, Raemaekers JMM, Oyen WJG, Boerman OC, Mandigers CMPW, Goldenberg DM et al. Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. Clinical Cancer Research. 2003 Oct 1;9(10 II).