A phase I study of an anti-CD22-deglycosylated ricin a chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy

P. L. Amlot, M. J. Stone, D. Cunningham, J. Fay, J. Newman, R. Collins, R. May, M. McCarthy, J. Richardson, V. Ghetie, O. Ramilo, P. E. Thorpe, J. W. Uhr, E. S. Vitetta

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Abstract

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:lgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 μg/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (≥ 1010/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Original languageEnglish (US)
Pages (from-to)2624-2633
Number of pages10
JournalBlood
Volume82
Issue number9
StatePublished - Nov 1 1993

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Ricin
Immunotoxins
B-Cell Lymphoma
Toxicity
Cells
Lymphoma
Therapeutics
Rhabdomyolysis
Serum Albumin
Myalgia
Splenomegaly
Pulmonary Edema
Serum
Blood
Monoclonal Antibodies
Weight Gain
Area Under Curve
Blood Vessels
Half-Life
Edema

ASJC Scopus subject areas

  • Hematology

Cite this

A phase I study of an anti-CD22-deglycosylated ricin a chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. / Amlot, P. L.; Stone, M. J.; Cunningham, D.; Fay, J.; Newman, J.; Collins, R.; May, R.; McCarthy, M.; Richardson, J.; Ghetie, V.; Ramilo, O.; Thorpe, P. E.; Uhr, J. W.; Vitetta, E. S.

In: Blood, Vol. 82, No. 9, 01.11.1993, p. 2624-2633.

Research output: Contribution to journalArticle

Amlot, PL, Stone, MJ, Cunningham, D, Fay, J, Newman, J, Collins, R, May, R, McCarthy, M, Richardson, J, Ghetie, V, Ramilo, O, Thorpe, PE, Uhr, JW & Vitetta, ES 1993, 'A phase I study of an anti-CD22-deglycosylated ricin a chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy', Blood, vol. 82, no. 9, pp. 2624-2633.
Amlot, P. L. ; Stone, M. J. ; Cunningham, D. ; Fay, J. ; Newman, J. ; Collins, R. ; May, R. ; McCarthy, M. ; Richardson, J. ; Ghetie, V. ; Ramilo, O. ; Thorpe, P. E. ; Uhr, J. W. ; Vitetta, E. S. / A phase I study of an anti-CD22-deglycosylated ricin a chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. In: Blood. 1993 ; Vol. 82, No. 9. pp. 2624-2633.
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