Imatinib (Gleevec)

General information

Class/mechanism: Tyrosine kinase inhibitor, inhibits multiple tyrosine kinases, including Bcr-Abl tyrosine kinase, the constitutively active tyrosine kinase resulting from the Philadelphia chromosome abnormality in CML; the receptor tyrosine kinases for platelet-derived growth factor (PDGF), stem cell factor (SCF), and c-kit, which is the activating mutation found in gastrointestinal stromal tumor (GIST) tumors.
Route: PO
Extravasation: n/a
Fertility: evidence of harm

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Dose adjustments

• Strong CYP3A4 inducers: increase starting dose by at least 50%, and carefully monitor
• Mild to moderate hepatic impairment: no adjustment needed
• Severe hepatic impairment: 25% decrease in recommended dose
• Mild renal impairment (CrCl 40 to 59): dose no greater than 600 mg/d
• Moderate renal impairment (CrCl 20 to 39): decrease starting dose by 50%, increase as tolerated but no greater than 400 mg/d
• Severe renal impairment: use with caution

Diseases for which it is used

• B-ALL, Ph+
• Chronic myelogenous leukemia
• Dermatofibrosarcoma protuberans (DFSP)
• Gastrointestinal stromal tumor
• Glioblastoma
• Hypereosinophilic syndrome
• Melanoma
• Systemic mastocytosis

Patient drug information

• Imatinib (Gleevec) package insert
• Imatinib (Gleevec) patient drug information (Chemocare)
• Imatinib (Gleevec) patient drug information (UpToDate)

History of changes in FDA indication

Chronic myelogenous leukemia

• 5/10/2001: Initial FDA approval for the treatment of patients with chronic myeloid leukemia (CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
• 12/20/2002: Additional indication for the treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (CML). (Indication expanded to first-line)
• 5/20/2003: Additional indication for the treatment of pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant or who are resistant to interferon alpha therapy. (Indication expanded to the relapsed/refractory pediatric population)
• 9/27/2006: Additional indication as a single agent for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML). (Pediatric indication expanded to first-line)

Dermatofibrosarcoma protuberans (DFSP)

• 10/19/2006: Additional indication for adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). (New disease entity)

Gastrointestinal stromal tumor

• 2/1/2002: Approved for the treatment of patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (New disease entity)
• 12/19/2008: Granted accelerated approval for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive gastrointestinal stromal tumor (GIST). (Indication extended to the adjuvant setting)
• 1/31/2012: Granted regular approval for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive gastrointestinal stromal tumor (GIST). (Converted from accelerated to regular approval)

Hypereosinophilic syndrome (HES)

• 10/19/2006: Additional indications for adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion)
• 10/19/2006: Additional indications for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. (New disease entity)

Myelodysplastic syndrome

• 10/19/2006: Additional indication for adult patients with myelodysplastic/ myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. (New disease entity)

Ph+ ALL

• 10/19/2006: Additional indication for adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). (New disease entity)
• 1/25/2013: Additional indication for pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. (Indication expanded to the first-line pediatric population)

Systemic mastocytosis

• 10/19/2006: Additional indication for adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. (New disease entity)

Also known as

• Code names: CGP 57148, CGP57148B, STI-571
• Generic names: imatinib mesilate, imatinib mesylate
• Brand names: Enliven, Glivec, Gleevac, Gleevec, Imalek, Imatib, Temsan, Veenat