29 March 2014

New chemotherapeutic regimen for Chronic Lymphocytic Leukaemia: A rare form of cancer

Chronic lymphocytic leukaemia (also known as CLL) is a rare cancer of the blood and bone marrow where the condition of the patient deteriorates with the progress of the disease. It is the second most common type of leukaemia in adults and often predominantly found in middle aged patients.CLL is a disease characterized by gradual increase in abnormal white blood cells counts.

Normally within our body mature blood cells are produced from blood stem cells (immature cells). Any particular blood stem cell has a possibility to develop into either a myeloid stem cell or a lymphoid stem cell. A myeloid stem cell could proliferate into one of three types of mature blood cells; RBC, WBC, or platelets. On the other hand, a lymphoid stem cell could proliferate into a lymphoblast cell and gradually develop into one of three types of lymphocytes; B lymphocytes, T lymphocytes, or Natural killer cells  and these are also known as white blood cells.

But for patients suffering from CLL, a major portion of blood stem cells become abnormal lymphocytes and do not proliferate to form healthy white blood cells. As a result large number of abnormal lymphocytes that couldn’t proliferate to healthy white blood cellsgets accumulated in the blood. These abnormal lymphocytes are known as called leukaemia cells. These abnormal lymphocytes cannot help to fight infections in the body very well and this increased number of lymphocytes in the blood and bone marrow provide less room for healthy white blood cells, red blood cells, and platelets. This abnormal distribution of blood cells triggers easy infection, anaemia, and bleeding in the patients suffering from this disease.

US-FDA approved Imbruvica in Feb 2014 for the treatment of chronic lymphocytic leukaemia (CLL) in patients who have received at least one previous market available therapy. This approval provides a new horizon for the CLL patients who became nonresponsive to previous treatments and where cancer has progressed to an advanced stage despite providing treatment and thus currently are looking for a new alternative effective treatment regimen.

Imbruvica works by selectively inhibiting Bruton’s Tyrosine kinase (BTK). BTK is an enzyme found to be constitutively active in CLL. Thus by inhibiting the BTK activity, this drug inhibits cancer cell growth and proliferation. BTK Inhibitors are under research and has proven to be effective for treatment for Chronic Lymphocytic Leukaemia (CLL) and some other forms of Leukaemia. Imbruvica has been categorized as orphan-product because it was developed for treatment of a rare disease.

FDA approved Imbruvica based on the report of a clinical study in which 48 subjects participated. These patients were diagnosed with CLL, average 6.7 years before the study and they have received prior therapies. All the study participants received an oral dose of 420 mg Imbruvica until the treatment reached unacceptable toxicity or the disease progressed. The result of the trial showed significant efficacy and for 58% of the participants, there was an effective reduction in cancer cells. At the time of the study the duration of response to the drug in patients ranged from 5.6 to 24.2 months.

The approval of Imbruvica was based on overall response rate in participants; however improvements in survival or disease-related symptoms have not been established and are subjected to further study. The approval of Imbruvica was categorized under FDA’s accelerated approval process. This approval process was intended to help patients by rapid availability of the drugs after clinical trial for the treatment of serious, rare disease conditions. Drugs which have received accelerated approval are subjected to future confirmatory trials and should further be verified on basis of safety and efficacy data and this same rule is applicable for Imbruvica too.

The serious side effects caused by the drug include bleeding problems, infections, kidney problems, and second primary cancers. Blood in stools or black stools, pink or brown urine, unexpected bleeding, blood vomiting & blood clots could also occur in patients as manifestations related to bleeding problem. In some cases, infections, kidney failure and even death have been reported with the use of Imbruvica. Even occurrence of new cancers in other organs has been reported in people treated with this drug. Other most common side effects includes, low levels of the platelets in the blood (Thrombocytopenia), diarrhoea, bruising, neutropenia, anaemia, upper respiratory tract infection, musculoskeletal pain, rash, fever, peripheral edema etc. This drug is not allowed to be taken along with grape fruit and oranges and should be avoided while taking CYP3A inhibitor and CYP3A inducer drugs.

Thus, Imbruvica provides new hope for the patients suffering from advanced level of CLL, who has been treated previously with at least one type of market available therapy and still developed treatment refractory cancer.  This drug also provides a new horizon of using BTK inhibitors as efficient treatment options for the treatment of advanced stage CLL.

Clinnovo is a clinical innovation company. It is pioneer CRO industry in India. Clinnovo offers professional Clinical Research Course, clinical data management course , SAS and imaging training. Clinnovo has been serving different bio-pharma industries across the world with excellence and high quality. For more information contact at +91 9912868928, 040 64635501

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