Responses in refractory hairy cell leukemia to a recombinant immunotoxin.
We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2. The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle. One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25(+) HCL.
Kreitman
R J
RJ
Laboratory of Molecular Biology, the Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Wilson
W H
WH
Robbins
D
D
Margulies
I
I
Stetler-Stevenson
M
M
Waldmann
T A
TA
Pastan
I
I
D036002:ADP Ribose Transferases; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000627:therapeutic use; D005098:Exotoxins / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A