Chronic Myeloid Leukaemia (CML)

Treatment Phase: Continuing treatment - third-line therapy

Clinical criteria:

  • Patient must have received initial PBS-subsidised treatment with this drug as a third-line therapy for this condition,

AND

  • Patient must have demonstrated a major cytogenic response of less than 35% Philadelphia positive bone marrow cells in the preceding 18 months and thereafter at 12 monthly intervals; OR

  • Patient must have achieved a peripheral blood level of BCR-ABL of less than 1% in the preceding 18 months and thereafter at 12 monthly intervals,

AND

  • The treatment must be the sole PBS-subsidised therapy for this condition.

Treatment criteria:

  • Must be treated by a medical practitioner; OR

  • Must be treated by a nurse practitioner where both of the following are occurring: (i) patient care is being shared with a medical practitioner, (ii) the prescription continues existing therapy with this medicine.

A major cytogenetic response [see Note explaining requirements] or a peripheral blood level of BCR-ABL of less than 1% on the international scale [see Note explaining requirements] must be documented in the patient's medical records.

Note

TREATMENT OF PATIENTS WITH CHRONIC MYELOID LEUKAEMIA - THIRD-LINE THERAPY

The following information applies to the prescribing under the Pharmaceutical Benefits Scheme (PBS) of tyrosine kinase inhibitors (TKI) agents for all phases of chronic myeloid leukaemia (CML) in the third-line treatment setting.

Where the term TKI agent appears in the following notes and restrictions it refers to dasatinib or nilotinib.

Patients are eligible for PBS-subsidised third-line treatment of CML if they have experienced treatment failure in the second-line treatment setting.

Patients are eligible for PBS-subsidised treatment with either dasatinib or nilotinib if they have not failed prior PBS-subsidised treatment with either dasatinib or nilotinib in the first-line or second-line treatment setting. Patients are eligible for PBS-subsidised treatment with either dasatinib or nilotinib at any one time and must not be receiving concomitant interferon alfa therapy. Eligible patients may only swap between these agents if they have not failed prior PBS-subsidised treatment with that agent and may only occur for reasons of intolerance.

Dasatinib is PBS-subsidised for all phases of CML (chronic, accelerated and blast phase) in the third-line treatment setting.

Nilotinib is PBS-subsidised for chronic and accelerated phase CML in the third-line setting. Nilotinib is not approved for patients in blast crisis in any (first, second, third-line) treatment setting.

Imatinib is not approved for third-line treatment of CML.

1. Initial third-line treatment

Third-line treatment with a TKI can only be approved when imatinib has been used for first-line treatment. Patients will only be approved for PBS-subsidised treatment with one third-line agent.

2. Continuing treatment for third-line treatment

For continuing applications, patients must demonstrate response to PBS-subsidised treatment as follows:

(i) within 18 months of the commencement of treatment, at which time patients in whom a major cytogenetic response or peripheral blood BCR-ABL level of less than 1% on the international scale (Blood 108: 28-37, 2006) has been demonstrated may receive authorisation for a further 12 months of treatment; and

(ii) at no greater than 12 month intervals thereafter, to demonstrate that the major cytogenetic response or peripheral blood BCR-ABL level of less than 1% has been sustained.

All pathology reports must be documented in the patient's medical records.

3. Authority approval requirements

Response criteria to initial treatment with dasatinib or nilotinib:

For the purposes of assessing response to PBS-subsidised treatment with dasatinib or nilotinib, either cytogenetic analysis indicating the number of Philadelphia positive [t (9;22)] cells in the bone marrow measured by standard karyotyping, or quantitative PCR indicating the relative level of BCR-ABL transcript in the peripheral blood using the international scale, must be conducted and the result must be documented in the patient's medical records. For bone marrow analyses, where the standard karyotyping is not informative for technical reasons, a cytogenetic analysis performed on the bone marrow by the use of fluorescence in situ hybridisation (FISH) with BCR-ABL specific probe must be conducted and the results must be documented in the patient's medical records. The cytogenetic or peripheral blood quantitative PCR analyses must be conducted and the results must be documented in the patient's medical records within 18 months of the commencement of treatment with dasatinib or nilotinib (patients in whom a major cytogenetic response or peripheral blood BCR-ABL level of less than 1% is demonstrable by 18 months are eligible to receive continuing treatment with that agent).

4. Definitions of response

A major cytogenetic response is defined as less than 35% Philadelphia positive bone marrow cells. A peripheral blood BCR-ABL level of less than 1% on the international scale (Blood 108: 28-37, 2006) also indicates a response, at least the biological equivalent of a major cytogenetic response.

5. Definitions of loss of response

Loss of a previously documented major cytogenetic response (demonstrated by the presence of greater than 35% Ph positive cells on bone marrow biopsy), during ongoing tyrosine kinase inhibitor (TKI) therapy. Loss of a previously demonstrated molecular response (demonstrated by peripheral blood BCR-ABL levels increasing consecutively in value by at least 5 fold to a level of greater than 0.1% confirmed on a subsequent test), during ongoing tyrosine kinase inhibitor therapy.

Note

Any queries concerning the arrangements to prescribe may be directed to Services Australia on 1800 700 270 (hours of operation 8 a.m. to 5 p.m. Monday to Friday).