From May 13–19, 2026, the 12th World Congress on Multiple Myeloma (COMy 2026) was held in Paris, France. As one of the most influential meetings in the field of multiple myeloma (MM), the congress brought together leading experts to discuss the latest advances in research, innovative therapies, and patient care.Among the highlights of the meeting was a landmark presentation by Professor Philippe Moreau of Nantes University Hospital, France, entitled “Frontline Treatment of Transplant-Eligible Multiple Myeloma Patients: A 35-Year Journey of IFM Clinical Research.” Through a comprehensive review of the French Intergroupe Francophone du Myélome (IFM) program, Professor Moreau charted the remarkable evolution of frontline MM therapy—from high-dose chemotherapy and autologous stem cell transplantation (ASCT) to modern immunotherapy-based quadruplet regimens and MRD-guided precision medicine.
His presentation not only showcased the milestones that have shaped current standards of care but also offered a glimpse into the future of individualized treatment strategies.
Establishing the Foundation: High-Dose Melphalan and Autologous Stem Cell Transplantation
The modern era of multiple myeloma treatment began with the recognition of a clear dose-response relationship for melphalan. Professor Moreau traced this concept back to the early 1980s, when investigators first demonstrated that escalating melphalan doses could improve anti-myeloma activity.
A true paradigm shift came in 1990 with the landmark IFM 90 trial, the first prospective randomized study to directly compare conventional chemotherapy with high-dose melphalan followed by autologous stem cell transplantation in newly diagnosed MM patients younger than 66 years of age.
The study demonstrated that ASCT significantly improved response rates, event-free survival, and overall survival compared with conventional treatment. These findings firmly established ASCT as the standard of care for transplant-eligible patients and ushered in a new era in myeloma management.
Subsequent efforts focused on optimizing transplant strategies. The IFM 94 study investigated the value of tandem transplantation and showed that a second ASCT could further improve progression-free survival, particularly in patients who failed to achieve a very good partial response after the first transplant.
At the same time, comparative studies of conditioning regimens demonstrated superior outcomes with melphalan 200 mg/m² (Mel200) compared with lower-dose melphalan combined with total body irradiation. As a result, Mel200 became—and remains—the global standard conditioning regimen before ASCT.
These pioneering studies not only cemented the role of transplantation but also created the platform upon which future risk-adapted and combination treatment strategies would be built.
Risk Stratification and Maintenance Therapy: From Thalidomide to Lenalidomide
As cytogenetic testing became more sophisticated, it became increasingly clear that multiple myeloma is a biologically heterogeneous disease with markedly different outcomes across patient subgroups.
Professor Moreau highlighted how the IFM group was among the first to integrate risk stratification into treatment planning.
The IFM 99 trials classified patients according to β2-microglobulin levels and chromosome 13 deletion status. These studies demonstrated that maintenance therapy with thalidomide significantly improved overall survival in standard-risk patients.
For high-risk patients, investigators compared tandem ASCT with ASCT followed by reduced-intensity allogeneic transplantation. Results favored tandem transplantation, suggesting that intensified consolidation strategies may be necessary to overcome adverse biological features.
The maintenance therapy landscape evolved further with the IFM 2005-01 study, which established the benefits of lenalidomide maintenance after transplantation.
The study showed a significant improvement in progression-free survival, and subsequent meta-analyses confirmed a broader survival benefit. Lenalidomide maintenance consequently became the worldwide standard following ASCT.
According to Professor Moreau, the transition from thalidomide to lenalidomide reflects not only advances in drug development but also the IFM group’s longstanding commitment to refining long-term treatment strategies through rigorous clinical investigation.
The Evolution of Induction Therapy: From Triplets to Immunotherapy-Based Quadruplets
Achieving deep remission before transplantation has consistently been associated with improved long-term outcomes.
Professor Moreau reviewed the progressive evolution of induction therapy over the past two decades.
The introduction of proteasome inhibitors marked the first major breakthrough. The IFM 2005 trial demonstrated that bortezomib plus dexamethasone (VD) produced superior response rates and progression-free survival compared with the historical VAD regimen.
Subsequent studies, including IFM 2007 and IFM 2013, evaluated triplet combinations incorporating immunomodulatory drugs. The VTD regimen (bortezomib, thalidomide, dexamethasone) consistently outperformed VD and VCD, establishing triplet therapy as the new standard.
Meanwhile, the influential IFM 2009 study demonstrated that the combination of VRD (bortezomib, lenalidomide, dexamethasone) plus ASCT provided superior outcomes compared with VRD alone, reaffirming the central role of transplantation even in the era of highly active induction regimens.
The transition to quadruplet therapy was driven by the landmark CASSIOPEIA trial, which randomized more than 1,000 transplant-eligible patients to receive VTD or daratumumab plus VTD (D-VTD) before and after ASCT.
The addition of the anti-CD38 monoclonal antibody significantly improved progression-free survival and ultimately overall survival, rapidly establishing quadruplet therapy as the preferred induction approach worldwide.
Professor Moreau emphasized that every step in this evolution—from doublets to triplets and now quadruplets—has been guided by improvements in hard clinical endpoints, particularly progression-free and overall survival.
The Era of Precision Medicine: MRD-Guided Treatment Decisions
As modern therapies continue to achieve unprecedented response depths, traditional response assessments based on serum markers and imaging are increasingly insufficient to guide treatment decisions.
Professor Moreau highlighted how the IFM group is helping lead the transition toward MRD-driven treatment strategies.
One of the most important ongoing studies is the MIDAS trial, which uses an induction regimen consisting of isatuximab combined with KRD (carfilzomib, lenalidomide, dexamethasone). Following induction, treatment decisions are guided by next-generation sequencing–based MRD assessment at a sensitivity level of 10⁻⁶.
Early results have been highly encouraging.
Approximately two-thirds of standard-risk patients achieved MRD negativity following induction therapy.
Perhaps even more striking, preliminary analyses suggest that among patients who achieve MRD negativity, there appears to be little difference in MRD outcomes between additional quadruplet-based consolidation and ASCT before maintenance therapy.
These observations raise a provocative question: could certain patients safely omit transplantation if sufficiently deep responses are achieved with modern immunotherapy-based regimens?
Professor Moreau cautioned that longer follow-up is needed, but the implications are profound. MRD negativity has consistently demonstrated a strong correlation with long-term progression-free survival and is increasingly viewed as a surrogate marker for durable disease control.
As a result, MRD assessment may soon become a central tool for treatment escalation or de-escalation, helping clinicians avoid overtreatment in low-risk patients while identifying those who may benefit from more intensive approaches.
Conclusion and Future Perspectives
Professor Philippe Moreau’s review of 35 years of IFM research provided a compelling overview of how frontline treatment for transplant-eligible multiple myeloma has evolved from empirical approaches to evidence-based standards and, increasingly, toward precision medicine.
From the establishment of high-dose melphalan and ASCT as the cornerstone of therapy, to the optimization of maintenance strategies with immunomodulatory agents, and from triplet induction regimens to CD38 antibody–based quadruplets, each advance has been driven by carefully designed clinical trials and a relentless commitment to improving patient outcomes.
Today, MRD-guided treatment strategies are beginning to challenge long-standing assumptions about the necessity of transplantation for all eligible patients. At the same time, emerging immunotherapies—including bispecific antibodies and other novel immune-based approaches—are rapidly moving into earlier lines of treatment.
As the field continues to evolve, the ultimate goal remains unchanged: achieving durable disease control, and ultimately, curing multiple myeloma.
The message from COMy 2026 is clear—after 35 years of remarkable progress, the journey toward that goal is accelerating.
