Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).
BACKGROUND
Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known.


METHODS
Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (Ind(IM)) or multiagent, age-adapted chemotherapy (Ind(chemo)). Imatinib was subsequently coadministered with consolidation chemotherapy.


RESULTS
In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to Ind(IM) and 50% in patients allocated to Ind(chemo) (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Ind(chemo); none failed imatinib induction. Severe adverse events were significantly more frequent during Ind(chemo) (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% +/- 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002).


CONCLUSIONS
In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction.
Ottmann
Oliver G
OG
Department of Hematology, University Hospital of Frankfürt, Germany. ottmann@em.uni-frankfurt.de
Wassmann
Barbara
B
Pfeifer
Heike
H
Giagounidis
Aristoteles
A
Stelljes
Matthias
M
Dührsen
Ulrich
U
Schmalzing
Marc
M
Wunderle
Lydia
L
Binckebanck
Anja
A
Hoelzer
Dieter
D
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D015996:Survival Rate
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate