A phase I dose-finding trial of recombinant interleukin-21 and rituximab in relapsed and refractory low grade B-cell lymphoproliferative disorders.
OBJECTIVE
We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies.


METHODS
One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.


RESULTS
Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).


CONCLUSIONS
Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted.
Division of Hematology & Oncology, University of California Los Angeles Medical Center, Los Angeles, California 90095-1678, USA. jtimmerman@mednet.ucla.edu
John M
JM
Timmerman
John C
JC
Byrd
David J
DJ
Andorsky
Reiko E
RE
Yamada
Janet
J
Kramer
Natarajan
N
Muthusamy
Naomi
N
Hunder
John M
JM
Pagel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000009:adverse effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D000098546:Interleukin-21
D058846:Antibodies, Monoclonal, Murine-Derived; D007378:Interleukins; D011994:Recombinant Proteins; D000069283:Rituximab; D000098546:Interleukin-21