FIRST trial: Lenalidomide with dexamethasone beats standard chemotherapy for multiple myeloma

1. Progression-free survival was improved by about 3 months with continuous lenalidomide-dexamethasone compared to standard melphalan-prednisone-thalidomide.

2. Overall survival was also better with continuous lenalidomide-dexamethasone compared to melphalan-prednisone-thalidomide.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Multiple myeloma (MM) is a disease of plasma cells. Over proliferation of these antibody-producing white blood cells can damage both bones and bone marrow, leading to bone pain, atypical fractures and anemia due to bone marrow dysfunction. The MM cells also produce large amounts of antibodies, which may accumulate in the kidney and other tissues, leading to dysfunction.

MM can be treated with either chemotherapy alone or chemotherapy and a bone marrow transplant. Several chemotherapy regimen are available for MM patients who are not candidates for bone marrow transplantation, including melphalan-prednisone-thalidomide (MPT). More recent data suggested that lenalidomide and low-dose dexamethasone (Ld) may be effective and safe as a first-line chemotherapy regimen for MM.

This study found that Ld given continuously until disease progression was more effective at prolonging progression-free survival than either Ld given for 18 cycles or MPT given for 12 cycles. There was also a modest, but statistically significant improvement in overall survival associated with continuous Ld versus MPT. Additionally, continuous Ld was associated with a decreased risk of low white blood cell counts, but a higher risk of infection.

The strengths of this study include its large size (about 1600 patients) and the fact that it also included data on the performance of Ld for 18 cycles in relation to continuous Ld and MPT. There are many regimens for MM available, along with several others currently under investigation. More study will be needed to find the most effective therapy.

Click to read the study, published today in NEJM

Click to read the accompanying editorial in NEJM

Relevant Reading: Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial

In-Depth [randomized controlled trial]: This study randomized 1623 patients to three groups: continuous Ld, 18 cycles of Ld, and MPT. Patients were well matched at baseline. Median progression- free survival was about 3 months longer in the continuous Ld regimen versus MPT. Progression-free survival was about 4 months longer in continuous Ld versus 18 cycles of Ld. Patients treated with continuous Ld had greater progression-free survival as compared to those treated with MPT (hazard ratio 0.72; 95%confidence interval, 0.61 to 0.85; P<0.001). The continuous Ld group as well as the 18 cycles of Ld group both had greater response rates than the MPT group (75%, 73%, and 62%; P<0.001 for both comparisons). Overall survival at 4 years was 59% with continuous Ld and 51% with MPT (p=0.02). The incidence of grade 3 and 4 adverse events was similar between continuous Ld and MPT (85% and 89%). Neutropenia was less common with Ld (28% vs. 45%), but infections were more common (29% vs. 17%).

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