From the Journals

Trial supports less aggressive myeloma treatment



For patients with multiple myeloma that remains symptomatic within a year of starting therapy, neither a second autologous stem cell transplant nor more intensive consolidation therapy offered survival benefits superior to those seen with a single first autologous transplant and lenalidomide maintenance, reported investigators in a multicenter U.S. trial.

Histopathological image of multiple myeloma. Smear preparation of bone marrow aspirate stained with May-Grünwald-Giemsa procedure. Courtesy Wikimedia Commons/KGH/Creative Commons License

Among 758 patients with multiple myeloma (MM) who underwent standard induction therapy, followed by melphalan conditioning and autologous hematopoietic cell transplant (AHCT), there were no differences in either progression-free survival (PFS) or overall survival (OS) between the three treatment arms, reported Edward A. Stadtmauer, MD, from the University of Pennsylvania, Philadelphia, and his colleagues.

Patients were randomized to either lenalidomide (Revlimid) maintenance alone; consolidation therapy with four cycles of lenalidomide, bortezomib (Velcade), and dexamethasone (RVD), followed by lenalidomide maintenance; or second transplant followed by lenalidomide maintenance.

“Single AHCT followed by len[alidomide] remains the standard of care. Greater than 80% of patients were alive at 38 months, which highlights excellent contemporary outcomes of patients with MM when treated with a standard approach of a multidrug induction followed by AHCT consolidation and maintenance,” they wrote in the Journal of Clinical Oncology.

The investigators hypothesized that the use of thalidomide analogues and proteasome inhibitors used in first-line therapy, consolidation, and long-term maintenance after high-dose melphalan and AHCT would improve survival, compared with a second AHCT.

To test this idea, they enrolled 758 patients from 54 U.S. centers and randomized them to one of three post-transplant strategies prior to transplant conditioning with high-dose melphalan (200 mg/m2) and AHCT.

Roughly 25% of patients in each treatment arm had high-risk disease, defined as beta-2 microglobulin levels greater than 5.5 mg/L, high-risk cytogenetics, and deletion 13 detected by standard cytogenetics only. The remaining patients in each arm had standard-risk disease.

The patients, who were a median age of 56 years old, had symptomatic multiple myeloma 12 months from the start of therapy without disease progression. They were randomly assigned to either AHCT followed by a second transplant and lenalidomide maintenance (247 patients), single transplant followed by RVD and lenalidomide maintenance (254), or single AHCT plus lenalidomide maintenance (257).

There were no significant differences between the groups in the primary endpoint of PFS at 38 months, with rates of 58.5% for the dual AHCT plus lenalidomide group, 57.8% for AHCT/RVD/lenalidomide, and 53.9% for AHCT/lenalidomide. Respective OS rates also did not differ significantly, at 81.8%, 85.4%, and 83.7%.

Complete response rates at 1 year were 50.5%, 58.4%, and 47.1%, respectively.

The three regimens also were similar in their toxicity profiles and in the risk of second malignancies.

The trial was supported by grants from the National Institutes of Health, research groups, Celgene, and Millennium (Takeda) Pharmaceuticals. Dr. Stadtmauer reported ties to Celgene, Takeda, and other companies. Multiple coauthors reported relationships with industry.

SOURCE: Stadtmauer E et al. J Clin Oncol. 2019 Jan 17. doi: 10.1200/JCO.18.00685.

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