Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia

Robert J. Kreitman, Maryalice Stetler-Stevenson, Inger Margulies, Pierre Noel, David J.P. FitzGerald, Wyndham H. Wilson, Ira Pastan

Research output: Contribution to journalArticle

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Abstract

Purpose: To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL. Patients and Methods: Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts. Patients were stratified into three groups: response to cladribine less than 1 year, those with a response lasting 1 to 4 years, or no response and uncontrolled infection. Patients received BL22 40 μg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils ≥ 1,500/mm3, hemoglobin ≥ 11 g/dL, and platelets ≥ 100,000/mm3, were observed. Patients without HR were re-treated at 30 μg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1. Results: Thirty-six patients were enrolled including 26, nine, and one in groups 1 to 3. The response after one cycle (CR, 25%; PR, 25%) improved when 56% were re-treated (CR, 47%; PR, 25%). CR rate was similar in groups 1 and 2 (P = .7). Twenty-two with baseline spleen height lower than 200 mm had higher CR (64% v 21%; P = .019) and OR rates (95% v 36%; P = .0002) compared to 14 with spleens either absent or higher than 200 mm. The only serious toxicity was reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in two patients (6%). High neutralizing antibodies were observed in four patients (11%) and prevented re-treatment. Conclusion: BL22 activity in HCL is confirmed. Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy.

Original languageEnglish (US)
Pages (from-to)2983-2990
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number18
DOIs
StatePublished - Jun 20 2009
Externally publishedYes

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Hairy Cell Leukemia
Cladribine
Spleen
RFB4(dsFv)-PE38 recombinant immunotoxin
Immunotoxins
Hemolytic-Uremic Syndrome
Plasmapheresis
Splenomegaly
Splenectomy
Neutralizing Antibodies
Hemoglobins
Neutrophils
Blood Platelets

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kreitman, R. J., Stetler-Stevenson, M., Margulies, I., Noel, P., FitzGerald, D. J. P., Wilson, W. H., & Pastan, I. (2009). Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. Journal of Clinical Oncology, 27(18), 2983-2990. https://doi.org/10.1200/JCO.2008.20.2630

Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. / Kreitman, Robert J.; Stetler-Stevenson, Maryalice; Margulies, Inger; Noel, Pierre; FitzGerald, David J.P.; Wilson, Wyndham H.; Pastan, Ira.

In: Journal of Clinical Oncology, Vol. 27, No. 18, 20.06.2009, p. 2983-2990.

Research output: Contribution to journalArticle

Kreitman, RJ, Stetler-Stevenson, M, Margulies, I, Noel, P, FitzGerald, DJP, Wilson, WH & Pastan, I 2009, 'Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia', Journal of Clinical Oncology, vol. 27, no. 18, pp. 2983-2990. https://doi.org/10.1200/JCO.2008.20.2630
Kreitman RJ, Stetler-Stevenson M, Margulies I, Noel P, FitzGerald DJP, Wilson WH et al. Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. Journal of Clinical Oncology. 2009 Jun 20;27(18):2983-2990. https://doi.org/10.1200/JCO.2008.20.2630
Kreitman, Robert J. ; Stetler-Stevenson, Maryalice ; Margulies, Inger ; Noel, Pierre ; FitzGerald, David J.P. ; Wilson, Wyndham H. ; Pastan, Ira. / Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 18. pp. 2983-2990.
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abstract = "Purpose: To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL. Patients and Methods: Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts. Patients were stratified into three groups: response to cladribine less than 1 year, those with a response lasting 1 to 4 years, or no response and uncontrolled infection. Patients received BL22 40 μg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils ≥ 1,500/mm3, hemoglobin ≥ 11 g/dL, and platelets ≥ 100,000/mm3, were observed. Patients without HR were re-treated at 30 μg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1. Results: Thirty-six patients were enrolled including 26, nine, and one in groups 1 to 3. The response after one cycle (CR, 25{\%}; PR, 25{\%}) improved when 56{\%} were re-treated (CR, 47{\%}; PR, 25{\%}). CR rate was similar in groups 1 and 2 (P = .7). Twenty-two with baseline spleen height lower than 200 mm had higher CR (64{\%} v 21{\%}; P = .019) and OR rates (95{\%} v 36{\%}; P = .0002) compared to 14 with spleens either absent or higher than 200 mm. The only serious toxicity was reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in two patients (6{\%}). High neutralizing antibodies were observed in four patients (11{\%}) and prevented re-treatment. Conclusion: BL22 activity in HCL is confirmed. Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy.",
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AU - Wilson, Wyndham H.

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