Plenary session

In this highlights video from IMS 2026 in Glasgow, Prof Marie-Christiane Vekemans, senior hematologist at Cliniques Universitaires Saint-Luc in Brussels, reviews key findings presented during the plenary session.

First, updated results from the PERSEUS trial reinforce the role of daratumumab-VRd (D-VRd) induction and consolidation followed by daratumumab-lenalidomide maintenance in transplant-eligible patients. With approximately seven years of follow-up, the median progression-free survival (PFS) had not been reached with D-VRd, compared with 81 months with VRd, while six-year PFS was approximately 81% versus 56%, respectively. The reported PFS hazard ratio was approximately 0.35. Importantly, the protocol allowed daratumumab maintenance to be discontinued after two years in eligible patients. Among those able to stop treatment, approximately 75% remained treatment-free after a median follow-up of 44 months. PFS2 also remained more favorable when daratumumab was administered upfront, despite the possibility of receiving daratumumab at relapse in the comparator arm.¹

The phase III CERVINO trial evaluated etentamig, a novel BCMA-targeting bispecific antibody with a bivalent BCMA-binding site, low CD3-binding affinity, and an Fc structure permitting once-monthly administration following a single step-up dose. These characteristics are intended to enhance T-cell activation and myeloma cell killing while reducing cytokine release syndrome (CRS) and infections and facilitating administration outside academic centers. In the presented study, etentamig was compared with investigator’s choice of carfilzomib-dexamethasone, elotuzumab-pomalidomide-dexamethasone, or selinexor-bortezomib-dexamethasone. After a median follow-up of 11 months, in a population with a median age of 70 years and a median of three prior lines of therapy, the overall response rate was reported at 74% with etentamig as compared to 46% with investigator’s choice. A very good partial response (VGPR) or better was achieved in 63% vs. 20%, respectively, while MRD negativity at 10⁻⁵ approached 90% vs. 25%. Treatment was associated with a 60% reduction in the risk of progression or death, with benefit observed across subgroups. Lower rates of CRS and infections were also reported.²

The potential of T-cell-redirecting therapy to deepen responses was further illustrated by an IFM study presented outside the plenary session. Following six cycles of D-VRd induction, patients received treatment according to minimal residual disease (MRD) status. MRD-negative patients received teclistamab plus lenalidomide maintenance for two years, whereas MRD-positive patients received teclistamab plus talquetamab. In the latter group, all patients converted from MRD-positive to MRD-negative status. These findings provide additional evidence for investigating T-cell-directed immunotherapy as a means of achieving deeper responses after induction.³

The phase III EXCALIBER-RRMM trial evaluated the CELMoD iberdomide in combination with daratumumab and dexamethasone vs. daratumumab, bortezomib, and dexamethasone. CELMoDs have greater binding affinity for cereblon than immunomodulatory drugs, with the potential for increased myeloma cell killing and T-cell activation. Iberdomide may also offer advantages regarding non-hematologic toxicities such as rash and diarrhea and has demonstrated synergistic activity with daratumumab. In patients previously exposed to one or two lines of therapy who were not refractory to daratumumab, iberdomide-daratumumab-dexamethasone achieved an MRD-negativity rate of approximately 41%, compared with 21% in the comparator arm. This benefit was observed across subgroups, including lenalidomide-refractory patients, patients older than 75 years, and those with renal dysfunction. Neutropenia represented the principal toxicity but could be managed with growth-factor support. Rather than reducing the iberdomide dose, extending the interval between administrations was emphasized as the preferred approach when treatment modification was required. The study was also notable for the use of both PFS and MRD as dual primary endpoints, representing the first acceptance of MRD as a primary endpoint in combination with PFS in this context.⁴

Finally, early results were presented for an in vivo dual-targeting CAR T-cell approach directed against BCMA and CD19. This strategy could potentially address practical limitations of conventional CAR T-cell therapy by avoiding ex vivo manufacturing, reducing waiting time, and eliminating the need for bridging therapy associated with the manufacturing period. Among the first nine patients treated, five achieved a stringent complete response, one achieved a VGPR, and one achieved a partial response. Toxicity was limited, with only grade 1 CRS reported and no immune effector cell-associated neurotoxicity syndrome (ICANS) or delayed neurotoxicity.⁵ As such, these initial findings illustrate ongoing efforts to retain the therapeutic activity of CAR T-cell approaches while simplifying their delivery and potentially improving accessibility.