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Author(s): Sawyers CL (Sawyers, CL); Hochhaus A (Hochhaus, A); Feldman E (Feldman, E); Goldman JM (Goldman, JM); Miller CB (Miller, CB); Ottmann OG (Ottmann, OG); Schiffer CA (Schiffer, CA); Talpaz M (Talpaz, M); Guilhot F (Guilhot, F); Deininger MWN (Deininger, MWN); Fischer T (Fischer, T); O'Brien SG (O'Brien, SG); Stone RM (Stone, RM); Gambacorti-Passerini CB (Gambacorti-Passerini, CB); Russell NH (Russell, NH); Reiffers JJ (Reiffers, JJ); Shea TC (Shea, TC); Chapuis B (Chapuis, B); Coutre S (Coutre, S); Tura S (Tura, S); Morra E (Morra, E); Larson RA (Larson, RA); Saven A (Saven, A); Peschel C (Peschel, C); Gratwohl A (Gratwohl, A); Mandelli F (Mandelli, F); Ben-Am M (Ben-Am, M); Gathmann I (Gathmann, I); Capdeville R (Capdeville, R); Paquette RL (Paquette, RL); Druker BJ (Druker, BJ)
Title: Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study
Source: BLOOD 99 (10): 3530-3539
Date: 2002 MAY 15
Document Type: Journal : Article; Proceedings Paper
DOI: 10.1182/blood.V99.10.3530
Language: English
Comment:
Address: Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Heidelberg, Med Klin Mannheim 3, D-6800 Mannheim, Germany. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY USA. Hammersmith Hosp, ICSM, Dept Haematol, London, England. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Goethe Univ Frankfurt, Med Klin 3, D-6000 Frankfurt, Germany. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. CHU Poitiers, Dept Oncol Hematol & Cell Therapy, Poitiers, France. Univ Leipzig, Abt Haematol Onkol, Leipzig, Germany. Univ Mainz Klinikum, Med Klin & Poliklin 3, Mainz, Germany. Newcastle Univ, Royal Victoria Infirm, Dept Haematol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Osped San Gerardo, Hematol Sect, Monza, Italy. Natl Canc Inst, Dept Expt Oncol, I-20133 Milan, Italy. City Hosp Nottingham, Dept Haematol, Nottingham, England. Univ Victor Segalen, Lab Gregge Moelle, Bordeaux, France. Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. Hop Cantonal Univ Geneva, Div Hematol, Geneva, Switzerland. Stanford Univ, Sch Med, Div Hematol, Stanford, CA 94305 USA. Osped Policlin Sant Orsola Malpighi, Inst Ematol, Bologna, Italy. Azienda Osped Niguarda Ca Granda, Div Ematol, Milan, Italy. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Scripps Res Inst, Ida & Cecil Green Canc Ctr, La Jolla, CA USA. Tech Univ Munich, Med Klin & Poliklin 3, Munich, Germany. Univ Klin Kantonspital, Div Hematol, Basel, Switzerland. Univ Roma La Sapienza, Azienda Policlin Umberto I, Dipartimento Biotechnol Cedulari & Ematol, Rome, Italy. Novartis Pharmaceut, Basel, Switzerland. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Oregon Hlth & Sci Univ, Div Hematol, Portland, OR 97201 USA. Reprint: Sawyers, CL, Univ Calif Los Angeles, Dept Med, 11-934 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
E-mail: csawyers@mednet.ucla.edu
Author Keywords:
KeyWords Plus: TYROSINE KINASE INHIBITOR; BONE-MARROW-TRANSPLANTATION; CHRONIC
GRANULOCYTIC-LEUKEMIA; ABL-POSITIVE CELLS; BCR-ABL;
PHILADELPHIA-CHROMOSOME; ACCELERATED PHASE; DOSE CYTARABINE;
TERMINAL-PHASE; THERAPY
Abstract: Blast crisis Is the most advanced stage of chronic myelogenous leukemia (CML) and Is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase 11 trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib Induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with Imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs. (C) 2002 by The American Society of Hematology.
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