![]() Most of the randomized studies have included patients younger than 65 years of age and so it becomes difficult to infer conclusions regarding this matter 15. Two important conditions are described below. Generally, HDT/ASCT is reserved for patients younger than 65 years old with no severe comorbidities. There is no consensus regarding an age cutoff beyond which treatment with ASCT becomes questionable and as such, practice varies across institutions and countries. This review addresses ten questions around the different steps of transplantation and lays forward current evidence from ongoing trials to aid decision-making. The challenge is thus to evaluate the necessity of HDT/ASCT when a powerful monoclonal antibody is combined with an induction regimen incorporating an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI). ![]() Current ongoing studies are investigating incorporating different agents such as daratumumab and lenalidomide before and after transplantation, respectively. Thus, in the era of novel agents, embarking on transplantation is further scrutinized. The introduction of drugs such as thalidomide, lenalidomide, and bortezomib administered before and/or after HDT/ASCT gave way to the groundbreaking achievement of stringent complete response (sCR) with a normal kappa/lambda ratio (serum free light chain) 10, immunophenotypic CR 11, and molecular CR 12, in addition to significantly increased CR and CR plus very good partial response rate (VGPR) 13, 14. Even though standard, the procedure is still challenged by inevitable relapses threatening long-term remissions, and is therefore challenged by some myeloma experts who delay ASCT till relapse or progression 5, 8. Despite its confirmed significant impact on event-free survival (EFS), multiple trials failed to depict significant impact on overall survival (OS) 9. The procedure’s superiority was initially proven by the Intergroupe Francophone du Myeloma (IFM) and later confirmed by the UK Medical Research Council 5, 6, 7, 8. Thirty years after the work of Powles, Barlogie, and McElwain led to the initiation of the concept of high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) 2, 3, 4, transplantation remains the standard for treating newly diagnosed multiple myeloma in young and in select, fit, elderly patients. Multiple myeloma accounts for approximately 10% of hematologic cancers and 1% of all cancers in general 1. Who is most suited to undergo ASCT? Is there an age threshold that should not be surpassed? Should transplantation be embarked on early or is it reasonable to delay it? What are the optimal induction, consolidation, and maintenance therapies? What is the role of tandem transplantation in the era of novel agents and where do patient-specific cytogenetics come into the equation when deciding on treatment? These are some of the questions addressed in this review which we will attempt to answer with the latest currently available data. In light of these new advancements, new challenges arise in deciding on optimal practice. Novel agent use is now inarguably essential in induction, maintenance, and possibly consolidation. ![]() Not only did the arrival of novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and monoclonal antibodies not replace ASCT, instead they solidified its central role as standard of care. More than 30 years after its introduction, autologous stem cell transplantation (ASCT) remains the standard of care for young patients with newly diagnosed multiple myeloma.
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