Combo treatment: new standard for multiple myeloma?


Continuous treatment of multiple myeloma with an immune system modulator and a low-dose steroid outperformed standard care in older patients or those not eligible for stem cell transplant, according to a researcher at the annual meeting of the American Society of Hematology.

In an international, phase III trial, newly diagnosed patients taking lenalidomide (Revlimid) and low-dose dexamethasone were less likely to see the disease progress than those taking melphalan, prednisone, and thalidomide (Thalmid), according to Thierry Facon, MD, of the Lille regional university hospital center in Lille, France.

An interim analysis also suggested the two-drug combination improved overall survival (OS), without unexpected safety issues, Thierry told reporters at the annual meeting of the American Society of Hematology in New Orleans.

The trial "establishes continuous (lenalidomide/low-dose dexamethasone) as a new standard of care" in newly diagnosed patients who are not eligible for a stem cell transplant, Thierry said.

Indeed, the combination "has implications for helping us to convert multiple myeloma from an incurable condition to a more chronic stable condition, especially in older patients," commented Joseph Mikhael, MD, of the Mayo College of Medicine in Phoenix, who was not part of the study but who moderated a press conference at which details were presented.

The combination is "already considerably used" in North America, Mikhael said, but "not as prolifically in older patients, or patients not going to autologous stem cell transplant."

In the FIRST trial, Thierry and colleagues enrolled 1,623 patients worldwide who were either 65 and older or not otherwise eligible for transplant.

The patients were randomly assigned to one of three treatments -- continuous therapy with lenalidomide and dexamethasone, 72 weeks of the combination, or 72 weeks of standard therapy with melphalan, prednisone, and thalidomide.

The standard therapy is usually stopped after a period of time in order to reduce toxicity.

The primary endpoint of the study was progression-free survival (PFS), but Thierry also reported the outcome of an interim analysis of OS, where he said the data are not yet "mature."

After a median follow-up of 37 months, 127 of the continuously treated patients remained on therapy, he said, but all those in the other two arms had completed treatment.

For the primary endpoint, he said, the median PFS was 25.5 months for those getting continuous lenalidomide and dexamethasone.

By comparison, the medians for the other two arms were nearly identical at 20.7 months for the limited duration lenalidomide and dexamethasone and 21.2 months for melphalan, prednisone, and thalidomide.

The differences were significant (P=0.00001 and P=0.00006, respectively), Thierry said, and the respective hazard ratios were 0.70 and 0.72.

Put another way, after 36 months, 42% of those getting continuous lenalidomide and dexamethasone had not yet progressed, compared with 23% in each of the other two arms, he said.

In the interim analysis, measured after 574 deaths, 4-year OS was 59.4% for those getting continuous lenalidomide and dexamethasone, 55.7% or those getting limited lenalidomide and dexamethasone, and 51.4% for those on the standard care.

The safety profile for the continuous therapy was "manageable," Thierry said, with no unexpected adverse events. Relevant grade 3/4 adverse events for those receiving continuous therapy were infection (29%), neutropenia (28%), thrombocytopenia (8%), neuropathy and deep vein thrombosis (both at 5%), and febrile neutropenia (1%).

Interestingly, the incidence of hematological second primary malignancies was lower than in the standard- care arm (0.4% versus 2.2%).


Source: MedPage Today:

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