Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial.
BACKGROUND
Mastocytosis is characterized by the abnormal proliferation of mast cells in 1 or more organs. In most patients, a mutation is present in the gene for C-KIT, resulting in deregulation of the c-kit receptor. Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Therefore, the authors evaluated the efficacy and safety of imatinib mesylate as treatment for patients with systemic mastocytosis.


METHODS
Patients with systemic mastocytosis received imatinib mesylate orally at a dose of 400 mg once daily for 3 to 6 months. Low doses of prednisone were added during the first 2 weeks. Endpoints were reductions in serum tryptase, urinary N-methylhistamine excretion, skin lesions, the number of mast cells in bone marrow sections, hepatomegaly and/or splenomegaly, and symptoms.


RESULTS
Of 14 patients who were included in the study, 11 patients had the D816V mutation. One patient expressed the FIP1L1-PDGFR-alpha rearrangement gene. In 2 patients, no mutation was found. In 10 patients, serum tryptase levels decreased >20%. In all patients, urinary N-methylhistamine excretion was reduced. In 8 of 13 evaluable patients, the number of mast cells in the bone marrow decreased. Skin symptoms diminished in 5 of 9 patients. Hepatosplenomegaly improved in 3 of 6 patients. Symptoms decreased in 8 of 13 patients. In all patients who had the D816V mutation, reductions in > or =2 endpoints were achieved. In the patient who expressed the FIP1L1-PDGFR-alpha rearrangement gene, a complete response was attained. In general, imatinib mesylate was tolerated well.


CONCLUSIONS
Imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation.
Droogendijk
Helga J
HJ
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Kluin-Nelemans
Hanneke J C
HJ
van Doormaal
Jaap J
JJ
Oranje
Arnold P
AP
van de Loosdrecht
Arjan A
AA
van Daele
Paul L A
PL
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000473:pathology; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008407:Mast Cells / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008761:Methylhistamines / Q000652:urine; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D011995:Recombination, Genetic; D016896:Treatment Outcome; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
D000970:Antineoplastic Agents; D001549:Benzamides; D008761:Methylhistamines; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C048140:N-methylhistamine