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ASCO_2016_Photo by (c) ASCOTodd Buchanan.jpg

McCormick Place, site of
the ASCO Annual Meeting
© ASCO/Todd Buchanan

CHICAGO—Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant (ASCT) should be considered the standard of care in
newly diagnosed multiple myeloma (MM) patients, according to a meta-analysis presented at the 2016 ASCO Annual Meeting.

Lenalidomide maintenance increased overall survival (OS), with a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival.

Several studies have demonstrated that lenalidomide maintenance post-ASCT reduces the risk of disease progression or death in patients with MM by about 50%.

However, these studies were not powered for OS, said Philip McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York.

With this in mind, Dr McCarthy and his colleagues conducted a meta-analysis to assess the effect of post-ASCT lenalidomide maintenance on OS using a pooled analysis of primary source patient data. A search revealed 17 randomized, controlled trials using lenalidomide post-ASCT.

Three trials met pre-specified inclusion criteria and had sufficient OS events to test a treatment effect. The studies intended for lenalidomide maintenance to be given until progression.

In these trials, 1209 MM patients, with a median age of 58, were randomized from 2005 to 2009 to receive lenalidomide (605 patients) at 10 mg/day on days 1-21/28 or days 1-28/28. The remaining 604 patients served as controls. Baseline characteristics were generally balanced between the 2 groups.

With a median follow-up of 6.6 years, 491 patients (41%) had died.

After induction and single (82%) or tandem (18%) ASCT, 55% of patients achieved a complete response (CR) or very good partial response.

The median OS has not been reached in the lenalidomide arm but was 86 months for the control arm.

“There is a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival,” Dr McCarthy said.

The OS benefit favoring lenalidomide was generally consistent across the majority of subgroup analyses, including age, sex, ISS stage, response after ASCT, and prior induction therapy.

All studies contributed to the positive results of the meta-analysis. Heterogeneity tests showed significant differences across trials, mainly because of a difference in the magnitude of treatment effect, Dr McCarthy said.

The mean treatment duration of maintenance was 25 to 30 months in the lenalidomide group and 13 to 20 months in controls. About one-third to more than half of the patients received therapy for 3 or more years, Dr McCarthy said.

Lenalidomide led to an increased risk in the cumulative incidence of hematologic and solid tumor second primary malignancies. However, Dr McCarthy said the OS benefit of lenalidomide maintenance outweighs the risk of developing second primary malignancy.

“This large meta-analysis demonstrates that lenalidomide maintenance significantly prolonged OS post-ASCT, including in patients who achieved CR, demonstrating benefit in patients in all response categories,” Dr McCarthy said.

“Lenalidomide maintenance after ASCT can be considered a standard of care for newly diagnosed multiple myeloma patients. However, we have more to learn. Understanding the role of minimal residual disease detection and immune reconstitution after transplant should allow us to further improve OS. Critically, developing early endpoints as surrogates for long-term outcome and OS is important for the future. Otherwise, trials may continue for 10 years or longer.”

Dr McCarthy presented these findings as abstract 8001. end hematology article


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