U.S. ResidentsRELAPSED/REFRACTORY PHILADELPHIA CHROMOSOME—POSITIVE (Ph+) ACUTE LYMPHOBLASTIC LEUKEMIA
Acute lymphoblastic leukemia (ALL) is a relatively common leukemia, accounting for about 20% of all leukemias in adults.1,2
The Philadelphia (Ph) chromosome is the most frequent karyotypic aberration in adults with ALL.3
- The Ph chromosome results from the reciprocal translocation that fuses the BCR (breakpoint cluster region) gene from chromosome 22 to the ABL (Abelson tyrosine kinase) gene from chromosome 93
- This translocation [t(9;22)(q34;q11)] ultimately results in a constitutively active tyrosine kinase protein3
Epidemiology
Ph+ ALL occurs in 20% to 30% of adult patients with ALL overall, with the incidence rising to more than 50% in patients aged 50 years or older.3
Diagnosing Ph+ ALL
The process begins with cytology and immunophenotyping by flow cytometry, but cytogenetic and molecular genetic analyses are required to actually establish the diagnosis.4
A diagnosis of Ph+ ALL should be considered in patients with precursor-B ALL, particularly in those who are older and who coexpress myeloid markers.4
Presenting symptoms1
- Fatigue
- Dyspnea
- Dizziness
- Bleeding
- Easy bruising
- Infection
Prescribing GLIVEC
PRESCRIBING GLIVEC FOR Ph+ ALL PHILADELPHIA CHROMOSOME—POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
GLIVEC is indicated for the treatment of*:
- Adult patients with newly diagnosed Ph+ ALL integrated with chemotherapy1
- Adult patients with relapsed or refractory Ph+ ALL as monotherapy1
The recommended dose of GLIVEC is 600 mg/day for patients with Ph+ ALL. Hematologic experts in the management of this disease should supervise the therapy throughout all phases of care.1
Treatment schedule: On the basis of the existing data, GLIVEC has been shown to be effective and safe when administered at 600 mg/day in combination with chemotherapy in the induction phase, the consolidation and maintenance phases of chemotherapy for adult patients with newly diagnosed Ph+ ALL. The duration of GLIVEC therapy can vary with the treatment program selected, but generally, longer exposures to GLIVEC have yielded better results.1
For adult patients with relapsed or refractory Ph+ ALL, GLIVEC monotherapy at 600 mg/day is safe, effective, and can be given until disease progression occurs.1
| Dose Adjustments for Neutropenia and Thrombocytopenia in Ph+ ALL1 | ||
|---|---|---|
| Ph+ All (starting dose 600 mg) |
ANC <0.5 x 109/L and/or Platelets <10 x 109/L |
|
Response rates seen in patients with Ph+ ALL receiving GLIVEC 600 mg/day
| Effect of GLIVEC on relapsed/refractory Ph+ ALL2 | ||
|---|---|---|
| Phase 2 study (N=43)† | Phase 1 study (N=2) | |
| n(%) | n(%) | |
| Complete hematologic response (HR) (median duration of 3.4 months) | 8 (19%) | 2 (100%) |
| No evidence of leukemia (NEL) | 5 (12%) | |
| Return to chronic phase (RTC)/partial HR | 11 (26%) | |
| Major cytogenetic response (CyR) (median duration of 2.3 months) | 15 (35%) | |
| Complete CyR | 9 (21%) | |
| Partial CyR | 6 (14%) | |
* In patients, the effectiveness of GLIVEC is based on overall hematologic and cytogenetic response rates in Ph+ ALL. There are no controlled trials demonstrating a clinical benefit or increased survival for this disease.1
† A total of 48 patients with relapsed/refractory Ph+ ALL were studied, 43 of whom received the recommended GLIVEC dose of 600 mg/day. In addition, 2 patients with relapsed/refractory Ph+ ALL received GLIVEC 600 mg/day in a phase 1 study.2
References
References
- Faderl S, Jeha S, Kantarjian HM. The biology and therapy of adult acute lymphoblastic leukemia. Cancer. 2003;98(7):1337-1354.
- Cortes JE, Kantarjian HM. Acute lymphoblastic leukemia. A comprehensive review with emphasis on biology and therapy. Cancer. 1995;76(12):2393-2417.
- Thomas DA. Philadelphia chromosome-positive acute lymphocytic leukemia: a new era of challenges. Hematology Am Soc Hematol Educ Program. 2007:435-443.
- Ottmann OG,Wassmann B. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2005:118-122.
