88% Of Chronic Phase Patients With Ph+ CML Who Are Intolerant Or Resistant To Glivec Are Still Alive At 2 Years When Treated With Tasigna

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Blood / Hematology;  Cancer / Oncology
Article Date: 30 Jun 2009 - 3:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

New data show that at 24 months, patients in the chronic phase of Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML) who are intolerant or resistant to current first-line therapy (Glivec) experienced a rapid response and significant reduction in leukaemia burden when treated with 400mg Tasigna twice-daily1. Furthermore, the research shows that the majority of patients in both the chronic and accelerated phases of the disease are still alive at 2 years when treated with Tasigna1,2.

The results, presented at the 14th Congress of the European Haematology Association (EHA) in Berlin, Germany are based on a phase II single treatment study of 321 chronic phase, adult patients with Ph+ CML and 137 accelerated phase patients with Ph+ CML who were intolerant or resistant to the current gold-standard treatment Glivec1,2. The results substantiate data presented at the American Society of Haematology meeting in San Francisco last year.

The data show that response times were rapid with 94% of all patients reaching complete haematologic response (CHR) (meaning blood counts returned to normal) at a median of one month following initiation of therapy1. In patients that had not previously reached haematological response, 75% reached haematological response1. Complete cytogenic response (CCyR), meaning no Ph chromosomes could be detected in the bone marrow was reached by 44% of patients at a median of 3.3 months following initiation of therapy1.

Tasigna was specifically designed to inhibit Bcr-Abl (the protein responsible for the uncontrolled production of white blood cells that occurs in Ph+ CML patients) and mutations of Bcr-Abl more effectively than Glivec4. In preclinical studies, Tasigna was able to overcome resistance resulting from Bcr-Abl kinase mutations in 32 of 33 cell lines commonly associated with Ph+ CML and associated with Glivec intolerance4.

The data suggest that Tasigna can provide favourable long-term outcomes for these heavily pre-treated patient populations1. In this study Tasigna was generally well tolerated with most adverse events being mild and moderate1. No new safety issues emerged with 24 months follow up1. The most common adverse events were rash, headache and diarrhoea (experienced by 2% of patients)1. The most common haematological grade 3/4 abnormalities were neutropenia (31%), thrombocytopenia (31%) and anaemia (10%). However, brief dose interruptions were successful in managing most adverse events1.

Further data presented at EHA showed that 67% of Glivec resistant or intolerant patients with Ph+ CML in the accelerated phase of the disease were alive at 24 months with 20% of patients reaching CCyR and 70% of these patients maintained CCyR at 24 months2. Again, Tasigna was seen to be well tolerated with most side effects being mild to moderate. The most common non haematological grade 3/4 adverse events were rash and pruritus. The most frequent grade 3/4 haematological abnormalities were neutropenia (42%), thrombocytopenia (43%) and anaemia (27%)2.

A further study investigating the therapeutic efficacy and safety of Tasigna as a first-line therapy for newly diagnosed patients with Ph+ CML was also presented at EHA. The open-label, single-stage, multicenter phase II study involved 73 patients with newly diagnosed Ph+ CML3. The results of this study suggest that newly diagnosed patients with Ph+ CML in the chronic phase treated with Tasigna experienced faster and deeper responses than those taking Glivec3,5, when the results were compared with historical Glivec data. After 12 months of treatment, 96% of newly diagnosed patients treated with Tasigna had achieved CCyR3. Major molecular response (MMR) is achieved when no traces of Bcr-Abl (the protein that causes the proliferation of the cancerous cells that cause CML) is detected by laboratory tests. MMR is emerging as an important measure of treatment efficacy and may be the best predictor of long-term survival6,7. In this Tasigna study, 81% of all patients had achieved MMR at 12 months3. Historical data for Glivec show 70% of patients with the same attributes, being treated with 800mg imatinib a day reached CCyR at 12 months and 46% had achieved MMR over the same duration of time5. In this study, Tasigna was generally well tolerated with most adverse events being mild to moderate3.

CML is one of the most common leukaemias affecting 2,660 people in England and Wales8. Most people with CML can be treated in the long term with Glivec (imatinib) but a small amount of people cannot take Glivec because they experience side effects or because their cancer mutates and becomes resistant to Glivec9.

Sandy Craine, CML Support UK welcomes the new data: "The 24 month data further consolidates the potential of Tasigna to provide a real alternative not only for the small number of patients who do not respond or who experience side effects to Glivec, but also for those in later stages of CML. It is clear from these data that Tasigna offers a realistic opportunity to stabilise the disease, overcome the threat of progression and achieve long-term survival, which is the goal of everyone diagnosed with life-threatening conditions like CML."

In the UK and in more than 65 countries worldwide, Tasigna is indicated for the treatment of adults with chronic phase and accelerated phase Ph+ positive chronic myeloid leukaemia with resistance or intolerance to prior therapy including imatinib.

About Tasigna (nilotinib)

Taken orally, twice daily, Tasigna works by targeting the production of the Bcr-Abl protein, which is produced only by cells containing the Philadelphia chromosome4. This protein is recognised as the key driver of the overproduction of cancer cells in patients with Ph+ CML.

Applying experience gained from the development of Glivec, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Glivec. In preclinical studies, the medicine was able to overcome resistance resulting from Bcr-Abl kinase mutations in 32 of 33 cell lines commonly associated with Ph+ CML4. Tasigna was specifically designed to target the Bcr-Abl protein more preferentially than Glivec, without adding new mechanisms of action.

About Glivec

Glivec is approved in more than 90 countries including the US, EU and Japan for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumours (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasised). In Japan, Glivec is approved for the treatment of patients with Kit (CD117)-positive GIST. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukaemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukaemia (HES/CEL).

References

1. Kantarjian, H. Et al. Nilotinib in chronic myeloid leukaemia patients in chronic phase (CML-CP) with imatinib resistance or intolerance: 24 month follow up of a phase 2 study. European Society of Hematology (EHA). May 2009. Abstract 0627.

2. Hochhaus, A. Et al. Nilotinib in chronic myeloid leukaemia in accelerated phase (CML-AP) with imatinib resistance or intolerance: 24-month follow-up results of a phase 2 study. European Society of Hematology (EHA). May 2009. Abstract 0631.

3. Rosti, G. Nilotinib 800 mg daily in early chronic phase Chronic Myeloid Leukemia: 12-month results of a phase 2 trial of the GIMEMA CML working party. European Society of Hematology (EHA). May 2009. Abstract 1090. Oral presentation.

4. Tasigna (nilotinib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharma. Accessed May 2009

5. Cortes J, et al. A Phase III, Randomized, Open-Label Study of 400 Mg Versus 800 Mg of Imatinib Mesylate (IM) in Patients (pts) with Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints: 1-Year Results of TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity) Study. Abstract 335. American Society of Hematology, 2009.

6. Iacobucci I., Saglio, G., Rosti, G., et al. Achieving a Major Molecular Response at the Time of a Complete Cytogenetic Response (CCgR) Predicts a Better Duration of CCgR in Imatinib-Treated Chronic Myeloid Leukemia Patients Clin Cancer Res 2006;12 (10) May 15, 2006.

7. Ross, D., et. al. Limited clinical value of regular bone marrow cytogenic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL. .

8. NICE Guidance on the use of imatinib for chronic myeloid leukaemia - Technology Appraisal 70. October 2003.

9. O'Brien S, et al. International Randomized Study of Interferon Versus STI571 (IRIS) 7-Year Follow-up: Sustained Survival, Low Rate of Transformation and Increased Rate of Major Molecular Response (MMR) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib (IM). American Society of Hematology, 2009.

Source
European Haematology Association