A1) CML Alliance is a global program to help healthcare providers and their patients fully optimize therapy and achieve the best possible outcomes in the treatment of Ph+ CML.

CML Alliance provides support and educational materials for both healthcare professionals and patients.

For healthcare professionals, the program aims to provide or facilitate access to:

• Standardized molecular testing
• Educational information on the molecular biology and management of Ph+ CML
• Information about Ph+ CML clinical trials on investigational agents and existing therapies in Ph+ CML

For patients and caregivers, CML ALLIANCE offers:

• Unique programs designed to help patients better understand Ph+ CML, its treatment, and the importance of adherence to their Ph+ CML therapy
• Valuable educational information about living with Ph+ CML

The affiliates of Novartis AG believe that the best way to optimize therapy in all patients with CML worldwide is to provide these services as part of a single, integrated program. Services provided through CML Alliance are highly customized in each country in which it is offered, depending on local legal and regulatory specifications. In Europe, one example of an initiative developed in conjunction with CML ALLIANCE was the European Treatment and Outcome Study (EUTOS) for CML, which has had a major influence in increasing the number of Molecular Monitoring and Pharmacological Monitoring Centers and helped them to reach national and standardized status.¹For specific information and services available in each country, please contact your local Novartis organization.

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A2) Depending on local rules and regulations in each country, CML Alliance is available to patients with Ph+ CML, those taking TASIGNA^®, and those receiving GLIVEC^®.

A3) CML Alliance is a comprehensive program available in many countries around the world.

CML Alliance is customized in each country to best meet the local needs and regulatory and legal requirements of each country.

A4) CML Alliance fully complies with all privacy and confidentiality regulations of the countries in which it is implemented. For example, in the United States, CML Alliance complies with all HIPAA regulations.

A5) There is no cost to enroll this Program.

A6) GLIVEC^® led to a fundamental shift in care, as Ph+ CML evolved into a chronic disease that now requires long-term treatment. A decline in patient adherence can be an issue with long-term oral therapy.² Recent studies have demonstrated that decreased adherence plays a significant role in preventing patients from achieving optimal treatment goals.^3,4

The Hammersmith study demonstrated that adherence was the critical factor for achieving molecular responses and that adherence rate was the only independent factor that predicted complete molecular response (CMR). In fact, no CMR was observed when adherence was ≤90% (90% adherence is equivalent to missing 2 to 3 tablets per month). Moreover, no MMR was witnessed when adherence was ≤80%.³

The ADAGIO study reported similar findings, demonstrating a link between adherence and treatment outcomes⁴:

• Patients with suboptimal responses missed at least 7 daily doses each month, whereas patients with optimal responses missed only 1 or 2 daily doses each month
• Patients who failed to achieve CCyR missed at least 7 daily doses each month, whereas patients who achieved CCyR missed only about 3 daily doses each month

Nonadherence to treatment is a major issue in patients with chronic conditions who do not exhibit illness-related symptoms of their disease and may, over time, forget how important it is to take their therapy exactly as prescribed. Suboptimal adherence to oral therapy can lead to disease progression or death.²

A7) Evaluation of molecular response - the disappearance or reduction in BCR-ABL transcript levels, has significant prognostic
value in Ph+ CML therapy.⁵ Molecular responses help further evaluate the depth of a patient's hematologic and cytogenetic response to ensure that a patient's treatment is optimized over time.⁶

Molecular response has been found to correlate with both cytogenetic response and long-term progression-free
survival.⁵

Regular molecular testing is recommended by the NCCN guidelines and ELN Recommendations

NCNN guidelines

ELN guidelines

A8) RQ-PCR is the most sensitive method to determine the levels of BCR-ABL transcripts.⁵ RQ-PCR can detect a single BCR-ABL-positive cell per 105 normal cells, and changes in transcript levels can be detected even when cytogenetic changes are not evident.⁵

RQ-PCR results can differ considerably between labs and also drift over time for an individualized lab, making interpretation difficult. An international scale for reporting of BCR-ABL transcript measurements was established to minimize variation and allow for easy interpretation between laboratories.⁷ Standardized RQ-PCR allows physicians to evaluate results in relation to clinical trial data and consensus guideline recommendations to help optimize therapy for patients with Ph+ CML.

A9) Where permissible under local laws and regulations, CML Alliance will offer standardized RQ-PCR testing through certified laboratories that utilize the international scale. This will provide physicians with access to consistent and easily interpretable PCR results for better management of Ph+ CML patients.

Services through CML Alliance will be customized to best meet the needs and regulatory and legal requirements of each country. For specific information and services available in your country, please contact your local Novartis organization.