Anti-B4-blocked ricin: A phase II trial of 7 day continuous infusion in patients with multiple myeloma

Michael L. Grossbard, Panos Fidias, Jeanne Kinsella, John O'Toole, John M. Lambert, Walter A. Blattler, Dixie Esseltine, Ginny Braman, Lee M. Nadler, Kenneth C. Anderson

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM). Five patients with MM were scheduled to receive a 7 d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 μg/kg lean body weight (LBW)/d. Two patients received a 7 d infusion, one patient received 6 d, and another patient 5 d of therapy. The fifth patient was treated for 7 d at a lower dose of 30 μg/kg LBW/d because of the side-effects observed in the initial patients. Pharmacokinetic studies demonstrated a peak serum level >2.6 nm in three of the patients. Side-effects of therapy included hepatic transaminase elevations, myalgias, thrombocytopenia, nausea, vomiting, decrease in performance status and capillary leak syndrome. One patient developed HAMA and two patients HARA. One patient developed neurologic toxicity with akinetic mutism, and died following therapy. No patient demonstrated a significant decline in M-component during therapy. We concluded that anti-B4-bR can be administered by continuous infusion to patients with multiple myeloma, although immunotoxin levels >3 nM were associated with increased incidence of toxicity and required dose adjustment. Future trials using anti-B4-bR in MM will be needed to determine the optimal dose and administration schedule in this patient population and to determine whether there is evidence of biologic activity.

Original languageEnglish
Pages (from-to)509-515
Number of pages7
JournalBritish Journal of Haematology
Volume102
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Clinical trials
  • Immunotherapy
  • Immunotoxins
  • Monoclonal antibodies
  • Multiple myeloma

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