Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Abstract

The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy

“…Considering the latest data, active immunotherapy with CAR-T cells and BsAbs will soon revolutionize the therapeutic landscape of MM; thus, the stateof-the-art frontline treatment, including the transplant program, is expected to change in the next few years. Indeed, considering on one hand both the acute toxicities of HDM, such as hematologic and gastrointestinal toxicity, infections, and the long-term toxicities, such as secondary neoplasms [93], and considering also the significant increase in deep responses with quadruplet induction therapy and the great results of CAR-T cells and BsAbs treatment (see Table 2), it is likely that in the near future HDM-ASCT will be deferred or reserved for selected cases, leading to a risk-and a response-adapted therapy, improving the patient's quality of life and survival.…”