CML accounts for 15 pc in US: Dr. Nilesh D. Mehta

Patients develop symptoms of weakness, fatigue, anemia (low hemoglobin), enlargement of spleen that can lead to abdominal pain or discomfort, early satiety, weight loss, and night sweats. While symptoms for this disease can be varied, it is ultimately the blood test that detects this disease. WBC (white blood cells) are found to be elevated and careful examination of peripheral smear would provide clues for diagnosis of CML. For sake of simplicity, our blood cells are three types – red cells, white cells, and platelets. Patients with CML develop an elevation of white blood cells along with platelets. Patients develop anemia that causes symptoms of fatigue and weakness.

 

CML has been the paradigm for drug development in medicine and especially “target” drug development. IN the field of oncology, personalized and targeted drug therapy has transformed how we treat patients. It has been an extremely gratifying experience for clinicians to be involved in this major transformation of treatment options. Rather than destroy all the cells that come in your way, targets on cancer cells have allowed discovery of drugs that “selectively” destroy cancer cells thereby leaving non-malignant cells essentially untouched. The discovery of Philadelphia chromosome in 1960 made this disorder the first human cancer to be characterized by a chromosomal disorder.

 

Diagnosis of CML requires presence of BCR-ABL fusion gene and a bone marrow examination that confirms cytogenetic abnormality. Specialized testing on bone marrow will clinch the diagnosis of CML.

 

Therapy for this disease used to include drugs like busulfan, hydroxyurea, alpha interferon. Hydroxyurea is still utilized in a few patients for a short duration of time. One of the magnificent discoveries in medicine has been approval of imatinib in 2001. Dr. Brian J. Druker through his diligent research has been largely responsible for this major milestone in medicine. This drug revolutionized not only the management of this disease but has paved the path for multiple other targeted therapeutic strategy in other branches of medicine. Subsequent discovery of more powerful drugs like nilotinb and dasatinib has been further proof of scientific ingenuity and brilliance in treating this disorder.

 

Patients with CML can develop resistance to their initial treatment and additional therapeutic strategies need to be implemented. About 15% of patients are likely to develop resistance in their first 5 years of therapy. One of the unusual ways of resistance is through T315I mutation in which case both dasatinib and nilotinib do not have much of a role to play in the treatment. Bosutinib ( Bosulif ) was approved by US Food and Drug Administration in Septmeber 2012 for CML patients who were resistant to or intolerant to other treatments.

Another option for CML patients was introduction of subcutaneous injection of omacetaxine (Syrnibo) which was approved in October 2012. Most patients would prefer a pill over an injection, however, this discovery also adds another weapon in our armamentarium against CML.

 

Bone marrow transplantation used to be an actively used therapy in CML patients in the pre-BCR/ABL kinase inhibitor therapy era. Now, this aggressive therapy is reserved for patients who fail standard therapy with oral drugs. A patient who fails first line treatment with kinase inhibitor should be evaluated for high dose chemotherapy trial.

 

At the request of the US Food and Drug Administration (FDA), chronic myelogenous leukemia drug ponatinib (Iclusig), approved in December 2012, has been temporarily pulled from the market by its manufacturer, Ariad Pharmaceuticals. This is largely due to safety concerns and potentially life threatening side effects. While ponatinib has a unique advantage of providing benefit in certain refractory CML patients, the risks of blood clots, stroke, heart attacks was damaging and hence additional information is being sought. This certainly opens up discussions regarding a potentially successful and approved drug found to have some major issues after it has been released for general use.

 

Despite this disturbing news about ponatinib, treatment for CML includes multiple choices for clinicians and patients certainly are well served.

 

—- Dr. Nilesh D. Mehta