More Treatment Does Not Necessarily Mean More Benefit in Multiple Myeloma

Edward A. Stadtmauer, MD

Edward A. Stadtmauer, MD

More treatment does not necessarily offer more benefit for patients—at least when it comes to multiple myeloma.

According to the results of the phase III StaMINA trial evaluating posttransplant therapy in multiple myeloma, a second round of chemotherapy or stem cell transplant does not improve progression-free survival (PFS) or overall survival (OS) compared with the current standard course of treatment alone.

The addition of lenalidomide/bortezomib/dexamethasone (RVD) consolidation or a second autologous hematopoietic cell transplant (AHCT) was not superior to a single AHCT, followed by lenalidomide maintenance, in the upfront treatment of multiple myeloma.

“When compared with the current standard course of treatment alone, these data suggest that additions to standard multiple myeloma therapy do not improve benefit for patients,” said Edward A. Stadtmauer, MD, section chief of Hematologic Malignancies at the Abramson Cancer Center, University of Pennsylvania. “Based on these results, I believe that it would be reasonable to compare any new treatments to the standard therapy of melphalan followed by a single AHCT followed by lenalidomide maintenance.”

As Stadtmauer reported at the 2016 ASH Annual Meeting, despite remarkable advances in multiple myeloma therapy over the past decade, many patients will ultimately see their disease progress. Although lenalidomide maintenance after AHCT has improved PFS and OS, the role of additional interventions after AHCT, such as tandem AHCT or triple therapy consolidation, remains to be determined.

“There’s always room for improvement,” said Stadtmauer. “New therapies and interventions need to be actively investigated to see how much they further benefit the early treatment of patients with myeloma.”

From June 2010 to November 2013, researchers from 54 centers enrolled 758 transplant-eligible patients with symptomatic multiple myeloma. The patients, who were all within 2 to 12 months of initial therapy and without prior progression, were randomly assigned to receive either standard care (melphalan 200mg/m2 AHCT), standard care plus additional chemotherapy (4 cycles of RVD consolidation), or standard care plus a second round of AHCT. All arms included lenalidomide maintenance (at maximum tolerated dose up to 15 mg orally daily until progression) with dose modifications for toxicities.

Randomization was stratified by disease risk factors and center, and all patients were reviewed centrally for eligibility, response and progression. Of those enrolled, 24% were classified as high risk.

The primary objective was to compare 38-month PFS of the 3 treatment arms. PFS events included progression, nonprotocol anti-myeloma therapy, or death.

With almost all patients nearing the end of follow-up, the study’s Data and Safety Monitoring Board released the results Staudtmauer reported at ASH which showed no difference among the 3 groups in terms of the study’s primary endpoint.

At a median follow-up of 38 months, PFS was not significantly improved by these interventions: PFS rates were 52% in the single-transplant arm, 57% in the consolidation arm and 56% in the tandem transplant arm (P = .37).

Outcomes were also similar with respect to OS, said Stadtmauer. At 38 months, the corresponding probabilities of OS were 82.0%, 85.7%, and 83.4%, respectively.

In high-risk patients, PFS was between 40% and 48% at 38 months, with no difference in OS. Regarding the survival rate, Stadtmauer said it was “impressive that about 77% to 79% of high-risk patients are alive at 38 months.”

Finally, second malignancies emerged in 39 of the 758 patients (5.1%), including 15 in the consolidation arm, 14 in the tandem transplant arm, and 10 in the single-transplant arm. The most frequently reported secondary malignancies were leukemia in the tandem transplant and consolidation arms and solid tumors in the single AHCT arm.

“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, posttransplant consolidation with cycles of RVD or a second transplant do not produce incremental PFS benefit,” Stadtmauer concluded.

The researchers will continue to track long-term trends and outcomes of patients in a follow-up study.

Reference

Stadtmauer EA, Pasquini MC, Blackwell B et al. Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide and dexamethasone (RVD) consolidation with lenalidomide maintenance (ACM), tandem autoHCT with lenalidomide maintenance (TAM), and autoHCT with lenalidomide maintenance (AM) for upfront treatment of patients with multiple myeloma (MM): Primary results from the randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 — StaMINA Trial). Presented at: American Society of Hematology 58th Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract LBA-1.