Post-Transplant Maintenance Lenalidomide Effective for Myeloma

CHICAGO-Maintenance therapy with lenalidomide after autologous stem cell transplantation significantly prolonged survival in patients with multiple myeloma, according to the results of a meta-analysis presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 8001).

The data, presented by Philip L. McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York, showed that maintenance lenalidomide resulted in an estimated 2.5-year improvement in median overall survival, meaning that “lenalidomide is feasible for the long-term disease control after autologous stem cell transplant.”

According to McCarthy, autologous transplant is the standard of care for fit patients with newly diagnosed multiple myeloma; however, most patients who undergo transplant, even those who achieve a complete response, will eventually relapse or progress. Previous studies have shown that lenalidomide maintenance after transplant reduced the risk for disease progression or death by about 50%, but none of these studies were designed to evaluate overall survival as a primary outcome.

With this meta-analysis, McCarthy and colleagues evaluated whether post-transplant maintenance lenalidomide had any effect on overall survival. The meta-analysis included three randomized control trials where 1,209 patients were randomly assigned to lenalidomide 10 mg per day maintenance (n = 605) or no maintenance therapy after undergoing autologous stem cell transplantation (n = 604):

• CALGB 100104: Patients were assigned to placebo or maintenance lenalidomide with interim analysis and unblinding in December 2009, after which placebo patients who had progressive disease were allowed to crossover to lenalidomide treatment.

• IFM 2005-02: All patients received induction therapy with two cycles of lenalidomide and were then randomly assigned to placebo or maintenance lenalidomide. The interim analysis and unblinding took place in January 2010, but no crossover was allowed for placebo patients who had progressed.

• GIMEMA (RV-MM-PI-209): The study randomly assigned patients eligible for transplant to either consolidation with melphalan followed by transplant or 6 cycles of chemotherapy plus lenalidomide. Maintenance was continued until progression.

Although all three studies intended for lenalidomide to be given until disease progression, a second primary malignancy signal was detected at the end of 2010 in the IFM and CALGB studies. IFM elected to discontinue maintenance, while CALGB and GIMEMA continued lenalidomide maintenance.

With a median follow-up of 80 months, the median overall survival was not reached for the lenalidomide arm and was 86 months for the control arm, which equated to an approximately 26% reduction in death (HR, 0.74 [95% CI, 0.62–0.89]), representing an estimated 2.5-year increase in median survival.

Patients assigned to lenalidomide did have increased cumulative incidence of secondary primary malignancies for both hematologic malignancies (HR, 2.03; P = .015) and solid tumors (HR, 1.71; P = .032). However, in his conclusion, McCarthy said that the overall survival benefit of lenalidomide maintenance outweighs the risk of developing a second primary malignancy and that lenalidomide maintenance after transplant can be considered a standard of care.

McCarthy said that there was no qualitative heterogeneity between the studies included in the meta-analysis; however, there was quantitative heterogeneity, primarily related to the difference in magnitude of treatment effect primarily between the CALGB and IMF studies. Among the possible reasons for this heterogeneity including imbalances in pre-study characteristics between treatment arms within the individual studies, differences in induction regimens, differences in study conduct after unblinding and differences in frequency and type of second-line therapy.