The role of tandem autologous stem cell transplantation (ASCT) compared to single ASCT in the treatment of newly diagnosed multiple myeloma remains a topic of ongoing investigation. A recent article published in Nature provides a comprehensive analysis of existing data, shedding light on the potential benefits and limitations of tandem ASCT in the modern treatment landscape.
Efficacy of Tandem ASCT
Several studies have explored the efficacy of tandem ASCT, with varying results. Some trials have suggested a potential survival advantage with tandem ASCT, particularly in high-risk patients. Gagelmann et al. (2019) reported that tandem ASCT improved outcomes in newly diagnosed multiple myeloma patients with extramedullary disease and high-risk cytogenetics. Similarly, a meta-analysis by Chen et al. (2024) investigated the efficacy and safety of tandem transplant versus single stem cell transplant for multiple myeloma patients.
However, other studies have not shown a significant benefit. The GMMG-HD2 trial, reported by Mai et al. (2016), presented long-term results from a phase III trial comparing single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma, with no clear advantage for the tandem approach in the overall population.
Risk Stratification and Patient Selection
The key to determining the utility of tandem ASCT lies in risk stratification. High-risk multiple myeloma, characterized by specific genetic abnormalities or aggressive disease features, may benefit more from the intensified approach of tandem ASCT. Rees et al. (2024) discussed navigating high-risk and ultrahigh-risk multiple myeloma, highlighting challenges and emerging strategies.
ASCT in the Era of Novel Agents
With the advent of novel agents such as daratumumab, bortezomib, and lenalidomide, the treatment landscape for multiple myeloma has significantly evolved. Studies like CASSIOPEIA (Moreau et al., 2019) and GRIFFIN (Voorhees et al., 2020) have demonstrated the efficacy of these agents in combination with ASCT. The MAIA study, presented by Facon et al. (2024), showed the final survival analysis of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma.
The question remains whether tandem ASCT adds further benefit when these novel agents are incorporated into induction, consolidation, or maintenance therapy. The BMT CTN 0702 (STaMINA) trial (Hari et al., 2020; Stadtmauer et al., 2019, 2016) compared various post-autologous hematopoietic cell transplantation strategies, including tandem ASCT, but did not demonstrate a clear superiority of the tandem approach over other consolidation and maintenance strategies.
Considerations for Elderly Patients
Autologous stem cell transplantation is increasingly used in elderly patients with multiple myeloma. Studies by Merz et al. (2014, 2016) and Auner et al. (2015) have shown improved outcomes in elderly patients undergoing ASCT in the era of novel agents. However, the tolerability and benefit of tandem ASCT in this population require careful consideration.
Conclusion
The decision to pursue single or tandem ASCT in newly diagnosed multiple myeloma should be individualized based on patient risk factors, disease characteristics, and response to initial therapy. While tandem ASCT may offer a survival advantage in select high-risk patients, its role in the context of modern therapies and the potential for increased toxicity must be carefully weighed. Further research is needed to refine patient selection criteria and optimize the integration of tandem ASCT into treatment algorithms.
