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Lenalidomide, Bortezomib, and Dexamethasone Plus AHSCT Leads to Significant PFS Improvement in Myeloma

MM

A “highly significant” progression-free survival (PFS) benefit was reported with a triplet treatment plus autologous hematopoietic stem cell transplantation (AHSCT) compared with the triplet treatment alone in patients with newly diagnosed multiple myeloma (MM), according to research presented at the 19th Annual International Myeloma Society Meeting (IMS).

The research was presented by Paul G. Richardson, MD, clinical program leader and director of clinical research at the Dana-Farber Cancer Institute of Harvard Medical School. The data were from the phase III DETERMINATION trial.

The trial included patients newly diagnosed with MM who were randomized to receive three cycles of lenalidomide, bortezomib, and dexamethasone followed by stem cell mobilization and five more cycles (n=357), or melphalan 200mg/mplus AHSCT and two more cycles of lenalidomide, bortezomib, and dexamethasone (n=365). All patients received lenalidomide until progression or intolerance.

The median PFS was 46.2 months in patients treated with the triplet regimen and 67.5 months in patients treated with the triplet regimen plus AHSCT (hazard ratio [HR], 1.53; 95% confidence interval [CI] 1.23-1.91; P<.0001) at a median follow-up of 27 months.

In patients with high-risk cytogenetics, the median PFS was 17.1 months in the triplet regimen treatment arm and 55.5 months the triplet regimen plus AHSCT treatment arm (HR, 1.99; 95% CI, 1.21-3.26). In patients with standard-risk cytogenetics, the median PFS was 53.2 months the triplet regimen treatment arm and 82.3 months in the triplet regimen plus AHSCT treatment arm (HR, 1.38; 95% CI 1.07-1.79).

There was a complete response rate of 42% in the triplet regimen treatment arm and 46.9% in the triplet regimen plus AHSCT treatment arm.

The overall best response rate (defined as equal to or better than a partial response) was 95% in the triplet regimen treatment arm, and 97.5% in the triplet regimen plus AHSCT treatment arm. For patients with high-risk cytogenetics, it was 98.5% in the triplet regimen treatment arm and 97% in the triplet regimen plus AHSCT treatment arm. For patients with standard-risk cytogenetics, it was 94.4% for patients in the triplet regimen treatment arm and 97.8% in the triplet regimen plus AHSCT treatment arm.

The five-year overall survival (OS) rates were 79.2% for in triplet regimen treatment arm and 80.7% in the triplet regimen plus AHSCT treatment arm. In patients with standard-risk cytogenetics, the five-year OS rate was 86.2% in the triplet regimen treatment arm and 86% in the triplet regimen plus AHSCT treatment arm. In patients with high-risk cytogenetics, the five-year OS rate was 54.3% in the triplet regimen treatment arm and 63.4% in the triplet regimen plus AHSCT treatment arm.

“What is important to note is [there is] no overall survival difference [between treatments for high-risk patients], recognizing the median follow up now is well in excess of 18 months, and it’s similar between the two,” Dr. Richardson said during his IMS presentation. “But there may be important trends for high-risk again, in that regard, obviously, we look forward to further analysis.”

A preliminary analysis of minimal residual disease (MRD), which took place at the start of maintenance, indicated MRD-negative rates of 39.8% in the triplet regimen treatment arm and 54.4% in the triplet regimen plus AHSCT treatment arm.

Grade 3 or higher related adverse events were reported in 78.2% of patients receiving the triplet treatment and in 94.2% of patients receiving the triplet treatment plus AHSCT.

“In terms of conclusions and future directions, clearly the use of early transplant provided in the setting of [lenalidomide, bortezomib, and dexamethasone plus AHSCT] induction therapy [led to] strikingly superior PFS versus [lenalidomide, bortezomib, and dexamethasone] alone,” Dr. Richardson said. “And this was notably seen in the high-risk group compared to the standard risk. Obviously, though, we still need to do much more for our high-risk patients in the big picture.”

Richardson P, Jacobus S, Weller E, et al. Lenalidomide-bortezomib-dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression in patients with newly diagnosed multiple myeloma (NDMM), by cytogenetic risk. Oral Abstract #058. Presented at the 19th Annual International Myeloma Society Meeting; August 25-27, 2022.

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