Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein Enbrel in patients with refractory hematologic malignancies.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) is an important effector and regulatory cytokine involved in the pathophysiology of hematologic malignancies, including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative disorders (MPD). We conducted a pilot study to assess the safety of the soluble TNF receptor, etanercept (p75 TNFR:Fc; Enbrel) in patients with refractory hematologic malignancies.


METHODS
Patients were eligible if they had refractory HCL, CLL, AMM, or Philadelphia-negative MPD. Enbrel was administered twice weekly at a dose of 25 mg subcutaneously for a minimum of eight doses, and was continued in patients without overt progression.


RESULTS
Among the 26 patients enrolled on study, 25 patients were evaluable. Nine patients had AMM, eight CLL, three HCL, and five Philadelphia-negative MPD. Their median age was 60 years (range 30-83 years). A total of 70 courses consisting of 486 doses of Enbrel were administered. Enbrel was well tolerated, without any overt increase in infectious episodes. Stable disease/no objective response was seen in 22 patients (88%) and progression in 3 patients (12%). Three patients with AMM improved (two showed hematologic improvement, and one showed a reduction in liver and spleen size), and two patients (one with CLL and one with Philadelphia-negative MPD) showed improvement in disease-related symptoms.


CONCLUSIONS
Enbrel was well tolerated, but no responses were noted in these immunosuppressed patients with refractory hematologic malignancies.
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.
Apostolia-Maria
AM
Tsimberidou
Deborah
D
Thomas
Susan
S
O'Brien
Michael
M
Andreeff
Razelle
R
Kurzrock
Michael
M
Keating
Maher
M
Albitar
Hagop
H
Kantarjian
Francis
F
Giles
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068800:Etanercept; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D016896:Treatment Outcome
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept