High-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) is still the best option for multiple myeloma even after almost 2 decades with newer and highly effective induction agents, according to a recent systematic review and two meta-analyses.
Given the “unprecedented efficacy” of “modern induction therapy with immunomodulatory drugs and proteasome inhibitors (also called ‘novel agents’),” investigators “have sought to reevaluate the role of HDT/ASCT,” wrote Binod Dhakal, MD, of the Medical College of Wisconsin, and his colleagues. The report is in JAMA Oncology.
To solve the issue, they analyzed five randomized controlled trials conducted since 2000 and concluded that HDT/ASCT is still the preferred treatment approach.
Despite a lack of demonstrable overall survival benefit, there is a significant progression-free survival (PFS) benefit, low treatment-related mortality, and potential high minimal residual disease-negative rates conferred by HDT/ASCT in newly-diagnosed multiple myeloma, the researchers noted.
The combined odds for complete response were 1.27 (95% confidence interval, 0.97-1.65, P = .07) with HDT/ASCT, compared with standard-dose therapy (SDT). The combined hazard ratio (HR) for PFS was 0.55 (95% CI, 0.41-0.7, P less than .001) and 0.76 for overall survival (95% CI, 0.42-1.36, P = .20) in favor of HDT.
PFS was best with tandem HDT/ASCT (HR, 0.49, 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation (HR, 0.53, 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68, 95% CI, 0.53-0.87), compared with SDT. However, none of the HDT/ASCT approaches had a significant impact on overall survival.
Meanwhile, treatment-related mortality with HDT/ASCT was minimal, at less than 1%.
“The achievement of high [minimal residual disease] rates with HDT/ASCT may render this approach the ideal platform for testing novel approaches (e.g., immunotherapy) aiming at disease eradication and cures,” the researchers wrote.
The researchers reported relationships with a number of companies, including Takeda, Celgene, and Amgen, that make novel induction agents.
SOURCE: Dhakal B et al. JAMA Oncol. 2018 Jan 4. doi: 10.1001/jamaoncol.2017.4600.