Additional Interventions Do Not Boost Outcomes Over Single Transplant in Patients with Multiple Myeloma

Phoebe Starr

Multiple Myeloma


San Diego, CA—Additional interventions after upfront autologous hematopoietic stem-cell transplantation (HSCT) in patients with multiple myeloma failed to provide further improvement in progression-free survival (PFS) or overall survival (OS) compared with single autologous HSCT, according to results from the multicenter STaMINA clinical trial presented at the 2016 American Society of Hematology meeting.

The STaMINA clinical trial was the largest study that was conducted in patients with multiple myeloma in the United States and answered a question that was not previously studied in a head-to-head comparison. The results were presented by Edward A. Stadtmauer, MD, Hematologic Malignancies Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia.

The addition of consolidation therapy with lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone or a second autologous HSCT, was not superior to a single autologous HSCT, followed by lenalidomide maintenance in the treatment of patients with newly diagnosed multiple myeloma.

At a median follow-up of 38 months, the PFS rates were 52.2% with single autologous HSCT, 56.7% with autologous HSCT plus consolidation therapy, and 56.5% with tandem autologous HSCT (P = .37).

“In the era of thalidomide analogs and proteasome inhibitors used in the initial therapy for myeloma and the use of prolonged maintenance therapy with lenalidomide, post-transplant consolidation with cycles of lenalidomide, bortezomib, and dexamethasone or a second transplant do not produce incremental progression-free survival benefit,” said Dr Stadtmauer.

Lenalidomide maintenance therapy after autologous HSCT improves PFS and OS in patients with multiple myeloma. However, the role of additional interventions after transplant, including tandem transplant or triple-therapy consolidation, is not established.

The study sought to determine whether the use of novel agents (thalidomide analogs and proteasome inhibitors) as consolidation therapy with autologous HSCT, or a second autologous HSCT would improve survival over long-term maintenance therapy after high-dose melphalan plus autologous HSCT.

The STaMINA Clinical Trial

The STaMINA clinical trial, a 54-center, phase 3 study of the Blood and Marrow Transplant Clinical Trials Network, enrolled 758 transplant-eligible patients (24% with high-risk cytogenetics) aged ≤70 years (median age, 57 years) with symptomatic multiple myeloma within 12 months of initiating therapy and without disease progression.

“These patients were certainly treated in the era of novel agents,” Dr Stadtmauer said. More than 50% of the patients received induction therapy with lenalidomide, bortezomib, and dexamethasone.

Patients were randomly assigned to 1 of 3 treatment arms, all with lenalidomide maintenance therapy. Patients who were assigned to autologous HSCT plus consolidation therapy (N = 254) received melphalan 200 mg/m2 and autologous HSCT, plus 4 cycles of consolidation therapy with lenalidomide, bortezomib, and dexamethasone, followed by lenalidomide maintenance therapy; patients who were assigned to tandem autologous HSCT (N = 247) received melphalan 200 mg/m2 plus tandem HSCT, followed by lenalidomide maintenance therapy; and patients who were assigned to single autologous HSCT (N = 257) received autologous HSCT, followed by lenalidomide maintenance therapy.

At a median follow-up of 38 months, PFS was not significantly improved by the additional interventions. The Data Safety and Monitoring Board allowed the early release of the data. The PFS rate was 56.7% with autologous HSCT plus consolidation therapy, 56.5% with tandem autologous HSCT, and 52.2% with single autologous HSCT; the probabilities of OS were 85.7%, 82%, and 83.4%, respectively.

“High-risk [cytogenetic] patients did worse than standard-risk patients, but there were no differences by treatment arm,” Dr Stadtmauer said.

For standard-risk patients, the 38-month PFS was 59.5% with autologous HSCT plus consolidation therapy, 60.9% with tandem autologous HSCT, and 55.9% with single autologous HSCT; for high-risk patients, the 38-month PFS was 48.3%, 42.2%, and 40.2%, respectively. Approximately 78% of patients with high-risk disease were alive at 38 months.

Second primary malignancies were reported in 39 of the 758 (5.1%) patients, including 15 patients who received autologous HSCT plus consolidation therapy, 14 patients who received tandem autologous HSCT, and 10 patients who received single autologous HSCT. The most frequently reported second primary malignancy was leukemia in patients who received autologous HSCT plus consolidation therapy and tandem autologous HSCT, and solid tumors in patients who received single autologous HSCT and lenalidomide maintenance therapy.

The cumulative incidence of a new malignancy in the first 38 months was 6% with autologous HSCT plus consolidation therapy, 5.9% with tandem autologous HSCT, and 4% with single HSCT plus lenalidomide maintenance therapy.

“The results of this study suggest it would be reasonable to compare any new treatments with the standard therapy of melphalan, followed by a single auto-­transplant, followed by lenalidomide maintenance,” Dr Stadtmauer said.

The final analysis will be performed when all patients reach the 38-month follow-up milestone.