The development of an assay capable of predicting the response to the treatment of patients affected by CML with TKI is an outstanding result in itself which has been sought for by many researchers. In the framework of the activities which have been planned in the LeukoPredict project, in addition to the outstanding scientific and technical result, the assay will be brought to actual widespread adoption as a marketable In Vitro Diagnostic (IVD) Medical Device, backed up by industrial capability and worldwide commercial availability.
The growth impact for the company embraces many aspects:
• Increased revenue, leading to a doubling of the current revenue already two years after project completion (1.1 M€ to 2.2 M€)
• Increased employment, leading to 6 additional stable people hired within two years after project completion (Production 2 units, Research&Development 2 units, Sales&Marketing 1 unit, Administration 1 unit)
• Adoption of a new technology adding to the two main technologies on which current molecular diagnostics products are based (Reverse Line Blot and Real Time PCR)
• Establishment of company know-how and best practices for carrying out successful radical innovation in addition to the incremental innovation on which the company has built its gradual but steady growth since startup in 1987
The main societal impact is expected to come from huge cost savings for Healthcare Systems, allowing them to redirect their increasingly limited resources to other needs different from CML patient care.
For most CML patients in the chronic phase physicians are able to keep the disease under control with TKI treatment.
For these patients the device will increase quality of life thanks to the timely support to
- first-line therapy optimization in terms of efficacy and reduction of both adverse effects and probability of onset of primary resistance
- therapy optimization on therapy switch mandated by acquired resistance
Patients attempting therapy discontinuation will also benefit from therapy optimization in case of failure and therapy resuming.
There is also a potential to be investigated for therapy optimization in the accelerated and blastic phase.
In the recent European clinical practice guideline (European LeukemiaNet recommendations for the management of chronic myeloid leukemia:2013) the importance of quality of life improvement is acknowledged, including the issue of therapy discontinuation.
This is particularly relevant to fertile women who may have achieved an optimal response, because conception and pregnancy are contraindicated during TKI treatment.
The quality of life is also affected by the very fact that living together with a potentially fatal disease—CML is a cancer, after all—has emotional and social consequences affecting family and career planning and is accompanied by a variable level of uncertainty and fear. It was not surprising that both physical and mental health were reported to be better and closer to normal in the older than in the younger patients, because younger have more and different expectations, not only of a normal life, but also of a life free from leukemia and from treatment.
Currently, the major goal of therapy is survival, but it is acknowledged that living without treatment and without detectable leukemia will be a major issue for clinical investigation, requiring the achievement of a deeper molecular response.
An entirely new development can also be envisaged in the prediction of TKI response in general, i.e. also when treating diseases different from CML.
Numerous TKIs aiming at various tyrosine kinases have been proven to be effective anti-tumor agents and anti-leukemic agents, e.g. gefitinib and erlotinib aiming at the EGF receptor which are used for the therapy of non-small cell lung cancer (NSCLC), a lung cancer type accounting for about 80% to 85% of lung cancers.
Targeted therapies which are revolutionizing cancer therapy generally require so-called Companion Diagnostics (CDx) to check if the patient is a potential responder to the therapy. Various approaches are adopted in such IVD tests, resulting in different types of test, including e.g. mutation tests and immunohistochemistry tests, but generally some specific molecular feature correlated to response is detected.
For TKI drugs the more general approach adopted in this project of measuring the Tyrosine Kinase activity could be a generally applicable alternative, independently from proven correlations between specific molecular features and response, and as such capable of providing correct indications even when the response is driven by less frequent molecular features whose correlation is not yet proven or discovered.
Such development would open the application of the method to the prediction of response of tumors with much larger incidence than CML.
