From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives

Abstract

Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended.

Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy

“…Based on clinical evidence, the model assumed the rate of disease progression could be altered by patients receiving a maintenance therapy . Productivity losses for the population cohort were estimated for patients with NDMM not receiving maintenance therapy and compared with those receiving lenalidomide.…”

Adoptive immunotherapy with CAR modified T cells in cancer current landscape and future perspectives

“…Novel cell therapies and several potential targets for CAR T cells are under investigation in MM (45,46) (Table 2). Anti-CD38 and anti-SLAMF7 CAR T cells showed anti-MM effects in preclinical models (47,48), but the expression of both target antigens on other normal tissues including hematopoietic lineages and immune effector cells may cause off-tumor toxic effects limiting their long-term clinical use.…”

Is there still a role for stem cell transplantation in multiple myeloma?

“…High‐dose melphalan followed by autologous stem cell rescue is currently a worldwide standard of care for transplant‐eligible patients with newly diagnosed multiple myeloma (NDMM) . In Europe, chronological age has been used to define ASCT eligibility, particularly in clinical trials, with 65 years as a cutoff for defining ASCT‐eligible and ‐ineligible patients.…”

“…To date, allo‐SCT is not routinely recommended as part of the initial treatment of patients with NDMM because of the increased toxicity and the lack of a clear benefit for most patients. However, for young, selected, and motivated patients with high‐risk MM, allogeneic transplantation may be considered, preferentially in the context of a clinical trial …”

“…These studies have demonstrated that sASCT is a safe and effective treatment option for patients with relapsed and refractory MM. Both the American and European guidelines regard sASCT as a feasible treatment option for relapsed patients with previous adequate stem cell collection …”