Further progress in the treatment of multiple Myeloma?

Malik, Prabhat Singh ; Kumar, Lalit (2009) Further progress in the treatment of multiple Myeloma? The National Medical Journal of India, 22 (1). pp. 25-27. ISSN 0970-258X

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Abstract

The management of multiple myeloma (MM) has evolved over the past 2 decades from an incurable disease to a chronic illness. Recently, 2 new drugs-lenalidomide (a thalidomide analogue) and bortezomib (a proteosome inhibitor)-have been used for the treatment of MM. Treatment with bortezomib, dexamethasone and/or doxorubicin in relapsed/refractory MM is associated with a complete response rate of 30%.1 Based on these results, bortezomib has been approved for the initial treatment of this disease. This phase III trial included patients with newly diagnosed symptomatic, measurable MM who were not suitable for high dose chemotherapy and stem cell transplantation (SCT) because of age (>65 years) or coexisting conditions. It enrolled 682 patients (151 centres, 22 countries) and randomly assigned them to receive either bortezomib, melphalan and prednisone (n=344; bortezomib group) or melphalan and prednisone (n=338; control group). The baseline demographic and disease characteristics were comparable in the two groups. Patients received nine 6-weekly cycles of melphalan (9 mg/ m2) and prednisone (60 mg/m2) on days 1-4 alone or along with bortezomib (1.3 mg/m2) on 8 days each during cycles 1-4 and on 4 days each during cycles 5-9. The primary end-point of the study was time to disease progression. Secondary end-points included rate of complete response, duration of response, time to subsequent MM therapy and overall survival. Complete and partial responses were defined according to the European Bone Marrow Transplantation group (EBMT) criteria.2 Briefly, complete response was defined as absence of M protein in serum and urine confirmed in 2 samples by immunofixation, and <5% marrow plasma cells. Partial response was defined as reduction in the serum level of M protein of at least 50% and a reduction in the urine of at least 90%. Near complete response (very good partial response) was defined as complete response without confirmation of a decrease in marrow plasma cells to <5% by bone marrow biopsy, confirmation of the disappearance of M protein in serum or urine by repeat immunofixation, or both. Progressive disease was defined as any of the following: (i) absolute increase of >500 mg/dl of serum M protein compared with the nadir value; (ii) absolute increase of >200 mg of urinary M protein in 24 hours; (iii) new bone lesion or plasmacytoma; (iv) increase in the size of such lesions; or (v) development of hypercalcaemia (serum calcium level >11.5 mg/dl [2.9 mmol/L]). The data were analysed for time to progression, time to subsequent MM therapy and overall survival. For time to progression analyses, data from patients in whom there was no disease progression were censored at last assessment or at start of subsequent therapy. The response was evaluated in 337 patients in the bortezomib group and 331 in the control group. The partial and complete response rates were 71% and 30% in the bortezomib group, and 35% and 4% in the control group, respectively (p<0.001). The median duration of response was 19.9 months in the bortezomib group compared with 13.1 months in the control group. The median time to progression was 24 months in the bortezomib group and 16.6 months in the controls (hazard ratio [HR] bortezomib group: 0.48; p<0.001). This benefit in time to progression was independent of risk factors such as age, sex, race, baseline b2 microglobulin level, albumin level, geographical region, international staging (ISS)3 or creatinine clearance. The median time to subsequent therapy and the associated treatment-free interval were significantly longer in the bortezomib group than the control group (p<0.001). At a median follow up of 16.3 months, 45 patients (13%) in the bortezomib group and 76 (22%) in the control group had died (HR bortezomib group: 0.61; p=0.008). The median survival was not reached in either group. The estimated overall survival at 30 months in the bortezomib group was 83% compared with 67% in the control group.

Item Type:Article
Source:Copyright of this article belongs to All India Institute of Medical Sciences.
ID Code:86482
Deposited On:10 Mar 2012 13:20
Last Modified:10 Mar 2012 13:20

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