Listing of Pharmaceutical Benefits (NHL) - Schedule 4 part 1

Chronic Myeloid Leukaemia (CML)

Initial treatment - third-line therapy

The condition must be in the chronic phase; or

The condition must be in the accelerated phase; AND

Patient must not have failed PBS-subsidised treatment with this drug for this condition in the first-line setting; or

Patient must not have failed PBS-subsidised treatment with this drug for this condition in the second-line setting; AND

Patient must have documented failure with an adequate trial of PBS-subsidised first-line treatment with imatinib for this condition; AND

Patient must have failed an adequate trial of PBS-subsidised second-line treatment with dasatinib for this condition; AND

The treatment must not exceed a total maximum of 18 months of therapy with PBS-subsidised treatment with a tyrosine kinase inhibitor for this condition under this restriction; AND

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

Failure of an adequate trial of dasatinib is defined as:

(i) Lack of response to second-line dasatinib therapy, defined as either:

- failure to achieve a haematological response after a minimum of 3 months therapy with dasatinib for patients initially treated in chronic phase; or

- failure to achieve any cytogenetic response after a minimum of 6 months therapy with dasatinib for patients initially treated in chronic phase as demonstrated on bone marrow biopsy by presence of greater than 95% Philadelphia chromosome positive cells; or

- failure to achieve a major cytogenetic response or a peripheral blood BCR-ABL level of less than 1% after a minimum of 12 months therapy with dasatinib; OR

(ii) 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 dasatinib therapy; OR

(iii) 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 dasatinib therapy; OR

(iv) Development of accelerated phase in a patient previously prescribed dasatinib for the chronic phase of chronic myeloid leukaemia.
Accelerated phase is defined by the presence of 1 or more of the following:

(1) Percentage of blasts in the peripheral blood or bone marrow greater than or equal to 15% but less than 30%; or

(2) Percentage of blasts plus promyelocytes in the peripheral blood or bone marrow greater than or equal to 30%, provided that blast count is less than 30%; or

(3) Peripheral basophils greater than or equal to 20%; or

(4) Progressive splenomegaly to a size greater than or equal to 10 cm below the left costal margin to be confirmed on 2 occasions at least 4 weeks apart, or a greater than or equal to 50% increase in size below the left costal margin over 4 weeks; or

(5) Karyotypic evolution (chromosomal abnormalities in addition to a single Philadelphia chromosome); OR

(v) Disease progression (defined as a greater than or equal to 50% increase in peripheral white blood cell count, blast count, basophils or platelets) during dasatinib therapy in patients with accelerated phase chronic myeloid leukaemia, provided that blast crisis has been excluded on bone marrow biopsy.

Patients should be commenced on a dose of nilotinib of 400 mg twice daily. Continuing therapy is dependent on patients demonstrating a major cytogenetic response to nilotinib therapy or a peripheral blood BCR-ABL level of less than 1% within 18 months and thereafter at 12 monthly intervals.

A bone marrow biopsy pathology report demonstrating the patient has active chronic myeloid leukaemia, either manifest as cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1% on the international scale either on peripheral blood or bone marrow must be documented in the patient's medical records.

Pathology report(s) confirming a loss of response to imatinib and dasatinib, from an Approved Pathology Authority or details of the dates of assessment in the case of progressive splenomegaly or extramedullary involvement must be documented in the patient's medical records.