ASH 2024 Recap

Urine-free response criteria in MM

There were some interesting talks about urine-free response criteria when monitoring MM.  The limitations of urine measurement in MM monitoring, particularly for FLC, are well known.  Issues include:

• Difficulties in obtaining 24-hour urine samples from patients, and the storage and processing of these samples by clinical laboratories. 
• Urine protein electrophoresis has a lower analytical sensitivity compared to immunoassays that measure serum FLC,
• Due to the impact of the kidney metabolism on FLC levels,  urine FLC levels may not reflect disease burden accurately,

Only 28% of patients in the US provide a 24-hour urine sample when requested and one clinician reported that his patients prefer bone marrow biopsies to providing 24-hour urine samples.¹ 

Consequently, there is great interest in determining if urine measurements are necessary for MM monitoring.  This was directly addressed in one oral presentation and one poster , while several other talks mentioned this in passing.

Focus on precursor conditions

There was an increased focus on best practice in the management of precursor conditions such as monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma.  Management of monoclonal gammopathies of clinical significance, disorders that do not meet the diagnostic criteria for an active malignancy such as MM or Waldenström’s Macroglobulinemia, but where the monoclonal protein causes organ damage, was highlighted.  There was an educational session about these disorders, which stressed the importance of considering them in patients with MGUS to ensure optimal management.

Managing treatment-related secondary immunodeficiencies

As treatments become more aggressive, there is an increased risk of secondary immunodeficiencies in patients with MM and other hematological malignancies.  The International Myeloma Working Group’s 2024 guidelines on CAR-T and bispecific antibody treatments stress prophylaxis and supportive care, including intravenous immunoglobulin replacement therapy.  In many guidelines, this therapy is contingent on assessment of IgG levels.  

Mass Spectrometry

Throughout the conference there were several talks that described how patients with Multiple Myeloma can now achieve deeper responses with the use of combination therapies and therapeutic monoclonal antibodies. Considering the therapeutic advancements, experts emphasized the need for more sensitive diagnostic and monitoring techniques, as well as a category in the IMWG assessment criteria that captures results obtained by mass spectrometry.

Several presentations featured data that showed how mass spectrometry is a more sensitive tool than IFE, displays similar prognostic value compared to current MRD techniques (such as NGF and NGS) and may guide clinicians when to conduct invasive bone marrow assessment.