Decluttering responses and dynamic risk in multiple myeloma: how can we improve prognostication?

In this video, Prof Meera Mohan, haematologist at the Medical College of Wisconsin in Milwaukee (WI, USA) discusses the highlights of an oral abstract session at ASH 2024 dedicated to response assessment and prognostication in patients with multiple myeloma (MM).

A first of the abstracts selected by Prof Mohan assessed the long-term outcome of patients with functional high-risk MM (FHRMM) with and without high-risk features at diagnosis. (Ref. 1)

This analysis was based on data from the CoMMpass study and defined high-risk features as the presence of any HR cytogenetics(i.e., t(4;14), t(14;16), t(14;20), 1q amplification (amp1q) or 17p deletion(del17p)), the presence of a TP53 mutation or ISS-stage III disease. The analysis revealed that FHRMM patients have a poor prognosis regardless of their risk profiles at diagnosis. For example, FHRMM patients who relapse within 12 months of initial therapy have an overall survival (OS) of less than 24 months, regardless of the presence of high-risk features at diagnosis. As such, these findings identify a functional high-risk status as a useful tool to identify patients with poor prognosis and underscore the unmet medical need for this patient population. (Ref. 1)

A 24-hour urine (24HRU) collection is a key component of International Myeloma Working Group (IMWG) response criteria for MM. While these analyses are requested in clinical trials, they are often not part of routine clinical practice. In a secondary analysis of the phase III STAMINA trial, omitting 24HRU assessments from IMWG criteria changed <1% of responses and had no impact on PFS prediction at any response depth. The investigators therefore concluded that outside of situations such as AL amyloidosis (where 24HRU assessments remain critical), or in patients with urine as their only measurable MM biomarker, a 24HRU assessments can be omitted. (Ref. 2)

A third abstract was presented by investigators of the Mayo clinic and assessed the necessity of repeating biomarkers to confirm progressive disease in MM if two biomarkers ( i.e., serum M-protein [SPEP], urinary M-protein [UPEP] or serum free light chains [sFLC]) meet the progression criteria (‘simultaneous criteria’).(Ref. 3) This analysis, including a total of 434 patients,  showed that the presence of simultaneous criteria adequately identifies patients with true progressive disease, without overestimating the progression rate of myeloma. As such, confirmatory results of progression in relapsed MM patients who meet the progression criteria for two biomarkers at the same time are useless to determine disease progression. (Ref. 3)

A final presentation addressed in this video evaluated the impact of a prior autologous stem cell transplantation (ASCT) on the outcome of patients treated with BCMA-directed CAR-T cell therapy.(Ref. 4) Interestingly, patients who received a previous ASCT proved to have a significantly shorter median progression-free survival (PFS) following CAR-T infusion than patients who did not undergo this procedure (median: 9.5 vs. 21 months; p=0.01). In a subsequent multivariate analysis, adjusting for extramedullary disease, high-risk cytogenetics, R-ISS stage, LDH, and ferritin level, a previous ASCT continued to be independently associated with a significantly shorter PFS following CAR-T therapy (HR[95%CI]:  2.17[1.25-3.74]; p= 0.006). As such, these findings may be used to optimize the treatment sequence in patients with MM. (Ref. 4)