BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) usually are treated only for progressive disease. However, the discovery of biologic predictors of a high risk of disease progression, together with the development of newer, more targeted therapies, could change this paradigm. In this phase 2 study, the authors tested the safety and efficacy of early treatment for patients with high-risk CLL using alemtuzumab and rituximab. METHODS: Patients were eligible for treatment if they were 1) previously untreated, 2) had no National Cancer Institute-Working Group 1996 criteria for treatment, and 3) had at least 1 marker of high-risk disease 17p13-, 11q22-, or a combination of unmutated IgVH and CD38+/ZAP70+). Treatment consisted of subcutaneous alemtuzumab (initial dose escalation followed by 30 mg on Monday, Wednesday, and Friday for 4 weeks) and intravenous rituximab (375 mg/m(2) per week x4 doses). All patients received Pneumocystis pneumonia and herpes virus prophylaxis and were monitored for cytomegalovirus reactivation. RESULTS: Twenty-seven of 30 patients (90%) responded to therapy with 11 (37%) complete responses (CRs). Five patients (17%) patients who had a CR had no detectable minimal residual disease. The median response duration was 14.4 months, and only 9 patients required retreatment for progressive disease at the time of the current report (median follow-up, 17.6 months). Study patients had a significantly longer time from diagnosis to first treatment for CLL according to conventional indications than a comparison cohort with similar biologic risk profiles. CONCLUSIONS: The therapy regimen used was safe and effective for early treatment of patients with high-risk CLL. Further studies will be required to determine whether this early treatment strategy decreases morbidity and mortality for high-risk CLL. (c) 2008 American Cancer Society.
BACKGROUND:Patients with chronic lymphocytic leukemia (CLL) usually are treated only for progressive disease. However, the discovery of biologic predictors of a high risk of disease progression, together with the development of newer, more targeted therapies, could change this paradigm. In this phase 2 study, the authors tested the safety and efficacy of early treatment for patients with high-risk CLL using alemtuzumab and rituximab. METHODS:Patients were eligible for treatment if they were 1) previously untreated, 2) had no National Cancer Institute-Working Group 1996 criteria for treatment, and 3) had at least 1 marker of high-risk disease 17p13-, 11q22-, or a combination of unmutated IgVH and CD38+/ZAP70+). Treatment consisted of subcutaneous alemtuzumab (initial dose escalation followed by 30 mg on Monday, Wednesday, and Friday for 4 weeks) and intravenous rituximab (375 mg/m(2) per week x4 doses). All patients received Pneumocystis pneumonia and herpes virus prophylaxis and were monitored for cytomegalovirus reactivation. RESULTS: Twenty-seven of 30 patients (90%) responded to therapy with 11 (37%) complete responses (CRs). Five patients (17%) patients who had a CR had no detectable minimal residual disease. The median response duration was 14.4 months, and only 9 patients required retreatment for progressive disease at the time of the current report (median follow-up, 17.6 months). Study patients had a significantly longer time from diagnosis to first treatment for CLL according to conventional indications than a comparison cohort with similar biologic risk profiles. CONCLUSIONS: The therapy regimen used was safe and effective for early treatment of patients with high-risk CLL. Further studies will be required to determine whether this early treatment strategy decreases morbidity and mortality for high-risk CLL. (c) 2008 American Cancer Society.
Authors: Laura Z Rassenti; Lang Huynh; Tracy L Toy; Liguang Chen; Michael J Keating; John G Gribben; Donna S Neuberg; Ian W Flinn; Kanti R Rai; John C Byrd; Neil E Kay; Andrew Greaves; Arthur Weiss; Thomas J Kipps Journal: N Engl J Med Date: 2004-08-26 Impact factor: 91.245
Authors: S M O'Brien; H Kantarjian; D A Thomas; F J Giles; E J Freireich; J Cortes; S Lerner; M J Keating Journal: J Clin Oncol Date: 2001-04-15 Impact factor: 44.544
Authors: H Döhner; S Stilgenbauer; A Benner; E Leupolt; A Kröber; L Bullinger; K Döhner; M Bentz; P Lichter Journal: N Engl J Med Date: 2000-12-28 Impact factor: 91.245
Authors: D Huhn; C von Schilling; M Wilhelm; A D Ho; M Hallek; R Kuse; W Knauf; U Riedel; A Hinke; S Srock; S Serke; C Peschel; B Emmerich Journal: Blood Date: 2001-09-01 Impact factor: 22.113
Authors: Gerard Lozanski; Nyla A Heerema; Ian W Flinn; Lisa Smith; Jennifer Harbison; Jennifer Webb; Mollie Moran; Margaret Lucas; Thomas Lin; Marcy L Hackbarth; John H Proffitt; David Lucas; Michael R Grever; John C Byrd Journal: Blood Date: 2004-01-15 Impact factor: 22.113
Authors: Clive S Zent; Wei Ding; Susan M Schwager; Megan S Reinalda; James D Hoyer; Diane F Jelinek; Renee C Tschumper; Deborah A Bowen; Timothy G Call; Tait D Shanafelt; Neil E Kay; Susan L Slager Journal: Br J Haematol Date: 2008-03-27 Impact factor: 6.998
Authors: Sameer A Parikh; Michael J Keating; Susan O'Brien; Xuemei Wang; Alessandra Ferrajoli; Stefan Faderl; Jan Burger; Charles Koller; Zeev Estrov; Xavier Badoux; Susan Lerner; William G Wierda Journal: Blood Date: 2011-07-12 Impact factor: 22.113
Authors: Nisar A Baig; Ronald P Taylor; Margaret A Lindorfer; Amy K Church; Betsy R Laplant; Emily S Pavey; Grzegorz S Nowakowski; Clive S Zent Journal: Leuk Lymphoma Date: 2012-05-21