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According to an early-online article recently published in the Journal of Clinical Oncology, multiple myeloma patients with the genetic mutation referred to as t(4;14) may comprise a distinct subgroup that require individualized treatment approaches, particularly at the time of a cancer recurrence.

Multiple myeloma is a cancer of the blood that affects the plasma cells. Plasma cells are an important part of the immune system and produce antibodies to help fight infection and disease. Multiple myeloma is characterized by an excess production of abnormal plasma cells, which can result in symptoms such as increased risk for bacterial infections or impaired immune responses. Other effects of myeloma may include damage to the kidneys, osteoporosis, anemia and an elevated blood calcium level.

Outcomes among patients with multiple myeloma range significantly. This has led to an increase in research focused on specific patient or disease characteristics that may help predict outcomes following specific types of therapy. Ultimately, researchers hope that through understanding specific relationships between certain characteristics and outcomes among these patients, treatment may become more individualized.

Researchers from Canada recently conducted a clinical study to evaluate possible associations between the t(4;14) genetic mutation and responsiveness to certain therapies in patients with multiple myeloma. Patients with t(4;14) are known to have a poorer prognosis than patients without the mutation; however, researchers have not been able to explain the reason for the differences in prognoses.

The study included 131 patients with multiple myeloma; 19 of whom had t(4;14). Patients underwent initial therapy with a standard chemotherapy regimen referred to as VAD (vincristine, doxorubicin, and dexamethason) or dexamethasone alone. Patients were then to undergo treatment with high-dose chemotherapy.

Patients with t(4;14) had the following treatment outcomes:

• Nearly all patients (90%) achieved anti-cancer responses to initial therapy with VAD or dexamethasone.

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• 26% of patients experienced a cancer recurrence prior to administration of high-dose therapy.

• Median progression-free survival after high-dose therapy of only 14.1 months.

• No patient achieved anti-cancer responses to conventional-dose alkylating agents (cyclophosphamide or melphalan) following a cancer recurrence.

The researchers concluded that patients with multiple myeloma with a t(4;14) genetic mutation appear to comprise a distinct subgroup. Specifically, a large proportion of patients experienced a rapid cancer recurrence following standard initial therapy, while no patients appeared to achieve anti-cancer responses to standard alkylating agents following a cancer recurrence.

The authors suggest that multiple myeloma patients with t(4;14) may consider different therapeutic options including the participation in a clinical trial to improve their outcomes. Patients diagnosed with multiple myeloma may wish to speak with their physician regarding their individual risks and benefits of being tested for t(4;14) as well as consideration of different therapeutic strategies.

Reference: Jaksic W, Trudel S, Chang H, et al. Clinical Outcomes in t(4;14) Multiple Myeloma: A Chemotherapy-Sensitive Disease Characterized by Rapid Relapse and Alkylating Agent Resistance. Journal of Clinical Oncology. 2005; 23, No 28 (October 1), 2005: pp. 7069-7073.

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