ASH Highlights on Multiple Myeloma

Prof Claudio Cerchione, haematologist at the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy, was so kind to share his highlights on multiple myeloma from ASH 2023.

The EMN 17 Perseus study, focusing on frontline intervention in transplant-eligible patients with MM, has unveiled promising outcomes. The incorporation of daratumumab into the VRd regimen, in comparison to VRd, with daratumumab and lenalidomide-based maintenance, has exhibited notable advancements. Particularly, the study has demonstrated remarkable achievements in terms of both conventional efficacy parameters and more significantly, the depth of response. In the same setting, the IsKIa study, focusing on the comparison between isatuximab + KRd and KRd yielded compelling outcomes. Beyond demonstrating notable improvements in the overall response rate, Isa-KRd has exhibited noteworthy efficacy in achieving MRD negativity. The emphasis on MRD negativity is not only confined to the induction phase but extends across various temporal points, including post-transplantation and consolidation phases.

The attainment of MRD negativity has emerged as a pivotal endpoint in the evaluation of treatment efficacy. The proposition to consider MRD negativity as a primary endpoint for patients underscores a paradigm shift in the treatment approach for young, transplant-eligible patients, with an overarching objective of striving towards a potential cure for MM. The assessment of MRD in the context of MM warrants consideration beyond the confines of clinical trials, extending into routine clinical practice.

The updated data from the MonumenTAL-1 study with talquetamab presents noteworthy advancements in the realm of MM treatment. The observed overall response rate of approximately 70% is indeed remarkable, indicative of talquetamab’s pronounced efficacy in this patient cohort. Of particular significance is the substantial 50% response rate observed in individuals who had previously been exposed to other bispecific antibodies. This suggests a promising trajectory toward establishing a new standard of care.

Alnuctamab, a BCMA x CD3 TCE exhibits notable attributes, particularly in the context of subcutaneous administration and favourable tolerability. An additional key feature is the noteworthy MRD negativity rate, with 100% of the evaluated population achieving MRD negativity at the specified dosage, slated for use in upcoming trials. The imminent initiation of the phase 3 iLLUMINATE study, comparing alnuctamab to the standard of care within the same clinical context holds significant promise for elucidating its comparative efficacy.

The Asian Myeloma Network (AMN) conducted a phase 3 study that scrutinized the efficacy of pomalidomide, cyclophosphamide, dexamethasone (PCD) in comparison to pomalidomide and dexamethasone (PD) in the relapsed/refractory setting. While the observed PFS of 11 months may not be considered extensive, the study’s focus on the sequencing of treatments and the combination of PD with cyclophosphamide offers intriguing possibilities for future therapeutic approaches.

Ongoing initiatives are poised to make substantial contributions to the earlier diagnosis of MM. An illustrative example is the “Iceland Screens, Treats, or Prevents Multiple Myeloma” study (iStopMM), which constitutes a population-based screening initiative specifically targeting MGUS. The iStopMM study represents a significant step towards the early identification and intervention for individuals at risk of developing MM. Moreover, advancements in the molecular characterization of MM, such as gene expression profiling, particularly utilizing signatures like the SKY92 gene signature, coupled with state-of-the-art imaging tools like PET-CT in conjunction with full-body MRI, hold the potential to formulate a new prognostic score. The integration of advanced genomic profiling with cutting-edge imaging techniques aims to enhance the precision and accuracy of prognostic assessments in MM.

With the educational support of: