title: A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908).
abstract: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥ 65 years) patients (median age 76 years, n = 31) with treatment naïve progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m(2) weekly)(n = 16) or low dose (20 mg/m(2) 3x week)(n = 15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression-free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti-CD20 mAb therapy as a potentially more effective use of anti-CD20 mAb in the treatment of CLL.
authors.affiliation: University of Rochester Medical Center, Rochester, New York (Current Location) Mayo Clinic, Rochester, Minnesota (Former Location).
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.affiliation: Dana Farber Cancer Institute - ECOG-ACRIN Biostatistics Center, Boston, Massachusetts.
authors.forename: Xin
authors.initials: X
authors.lastname: Victoria Wang
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington (Current Location) University of New Mexico Cancer Center, Albuquerque, NM.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Libby
authors.affiliation: North Shore-LIJ Health System NCORP, Manhasset, New York.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Barrientos
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.affiliation: University of Wisconsin, Madison, Wisconsin.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Chang
authors.affiliation: Illinois CancerCare, Peoria, Illinois.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Kettering Health Network, Kettering, Ohio.
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Calvo
authors.affiliation: Case Western Reserve University, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York (Current Location) Northwestern University School of Medicine, Chicago, Illinois (Former Location).
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab; D000069283:Rituximab