Real-world outcomes of myeloma patients who fulfil the SLiM part only of the SLiM-CRAB criteria and who underwent monitoring during the COVID -19 pandemic: a single centre analysis

ABSTRACT

International Myeloma Working group (IMWG) diagnostic criteria for myeloma (MM) requires the presence of ≥10% clonal plasma cells alongside a MM defining event-traditionally a CRAB feature (hypercalcaemia, renal impairment, anaemia, bone disease). In 2014, three biomarkers were added (≥60% plasma cells in the marrow, light chain ratio ≥100 and ≥2 focal lesions on MRI), each associated with around an 80% probability of developing CRAB features within 2 years. These biomarkers are the SLiM criteria and the recommendation is that such patients are treated. In March 2020 UK Myeloma Forum issued guidance for MM therapy during the Covid-19 pandemic, recommending patients who fulfil the SLiM part only of the SLiM/CRAB (SLiM positive) or who only have anaemia should be monitored. There is a lack of real-world data available to validate the recommendation to treat based on SLiM criteria. The impact of not treating these patients during the Covid-19 pandemic remains unknown. We conducted a retrospective analysis of the outcomes of SLiM positive patients at Nottingham University Hospitals (NUH) NHS Trust who underwent observation rather than treatment during the Covid-19 pandemic. SLiM positive patients were detected via the MM MDT min from 1st April 2020-30 Nov 2021. Time to progression (TTP) was defined as the time from diagnosis of SLiM positive MM until the time systemic therapy was initiated (day 1 cycle 1). Decision to treat was based on development of CRAB features, worsening of SLiM criteria and patient choice. 22 SLiM positive patients were identified. Patient characteristics and outcomes for the entire cohort and for those who did and did not progress are shown in Table 1. No patients were R-ISS stage III and 1q gain was the only high-risk cytogenetic abnormality detected. This may suggest higher risk patients are more likely to present with CRAB features and less likely to be SLiM positive. The median follow-up was 12 months. Forty-one percent of patients progressed to require therapy in keeping with the IMWG data suggesting 80% of SLiM positive patients will progress over a 2-year period. The median TTP was not reached. For those patients who did progress, the median TTP was 3.8 months. Reasons for progression are shown in Table 1. Overall survival (OS) was 100% hence no suggestion thus far that observation of SLiM positive patients during the Covid-19 pandemic increased MM-related mortality. The majority who remained under observation were SLiM positive on WBMRI alone. In contrast, the majority who did progress had been SLiM positive on SFLC ratio, marrow infiltrate or a combination of features. We acknowledge the small numbers and relatively short follow-up of this study. Results thus far are in keeping with the IMWG finding that SLiM positive patients have around an 80% chance of progression at 2 years. There is a suggestion that patients who present with SLiM criteria only may have genomically lower risk disease. OS has not been affected thus far by monitoring SLiM patients. Our results also suggest that patients SLiM positive due to SFLC ratio or BM infiltration are more likely to require early intervention than those positive on WBMRI. We recommend a future multicentre UK wide analysis of the outcome of SLiM positive patients during Covid-19. Results would help counsel UK MM patients regarding when to offer treatment and potentially help develop a UK-based biomarker model to predict risk of progression..