The Role of Whole Body STIR MRI in Assessing First Biochemical Relapse in Patients with Myeloma
Authors: Rowland James , Mollee Peter 
Published: November 2020

Background: Myeloma remains an incurable disease and most patients will relapse. The optimal timing of salvage initiation remains uncertain although there is a trend to treating early biochemical relapse. In the current COVID-19 pandemic, delaying therapy of asymptomatic relapsed patients is also desirable, but avoidance of renal failure and symptomatic bony disease is important. Whole body STIR MRI with diffusion weighted imaging (DWI) has the potential to diagnose bone involvement at a very early, pre-symptomatic stage, before cortical destruction occurs. It may be a useful tool to assess the ability to defer therapy in myeloma patients with asymptomatic biochemical relapse.
Methods: We performed a retrospective audit of newly diagnosed patients with symptomatic myeloma, diagnosed between April 2012 and Oct 2019. We studied only patients in first relapse who had achieved PR or better to first-line therapy. Patients were typically monitored with monthly serum protein electrophoresis and free light chain assessments. The preferred imaging modality during the study period was whole body STIR MRI with DWI analysis and additional dedicated spinal sequences. Response and relapse criteria were as defined by the IMWG with the exception that regular urine BJP monitoring was not performed. Rapid biochemical relapse was defined as per Sonneveld (ASH Education Book 2017). The decision to initiate therapy for relapse was at the discretion of the treating hematologist.
Results: 125 patients with newly diagnosed symptomatic myeloma who achieved PR or better to first line therapy were identified. Median age at diagnosis was 64yrs (range, 32 to 89yrs) and 72% were male. Immunoglobulin type was IgG (54%), IgA (23%), light chain (22%) and IgD (1%). ISS stage was I (19%), II (60%) and III (21%) and 21% were high risk as defined by the presence of t(4;14), t(14;16) or del17p by bone marrow FISH. Half received autologous stem cell transplantation with bortezomib-based therapy being the commonest induction for both transplant- and non-transplant-eligible populations. Amongst this group with responsive disease, haematological response was CR (38%), VGPR (29%) and PR (33%).
75 (60%) of patients have relapsed at a median of 32 months. For patients in CR and VGPR, it took a median of 92 days from the first presence or increase in monoclonal immunoglobulin until IMWG defined relapse criteria were met. At the time of IMWG defined relapse, in terms of assessing need for therapy, the patients clinical status was defined as: rapid biochemical relapse (15%), relapse in a patient with high risk FISH (26%), relapse in a patient with renal failure at diagnosis (15%) and meeting CRAB criteria exclusive of MRI findings (7%), leaving 37% (n=27) in slow biochemical relapse without a definite indication for urgent therapy. MRI was performed as the bone imaging modality in 20 of these 27 slow biochemical relapse patients at a median of 42 days (range, -12 days to 210 days) after IMWG defined relapse: 10 demonstrated new focal bone lesions, 3 no lesions, 4 stable lesions and 3 improved bone lesions. Of these 10 patients with no new MRI detected bone disease, two were treated immediately at physician discretion.
Thus, only 8 of 75 relapses were asymptomatic with a normal MRI, had no other indication for urgent therapy and were observed. For this group, the median time to treatment was 96 days (range, 34 to 576 days). Of these 5 had therapy initiated at physician discretion in the absence of clinical deterioration at a median of 78 days post biochemical relapse, one had treatment started 38 days after relapse due to renal deterioration and two were observed for 6 months and 1.4 years prior to the development of progressive focal bone lesions on MRI. None of the 10 patients with slow biochemical relapse and no new focal MRI bone lesions developed symptomatic bone disease within 6 months of that normal MRI.
Conclusion: Whole body STIR MRI identifies new focal bone lesions in half of patients with slow biochemical relapse and no other treatment indication, justifying early therapy initiation at biochemical progression. In the setting of the COVID-19 pandemic, whole body STIR MRI with DWI may also be a useful tool to identify patients with slow biochemical relapse who are suitable for careful observation rather than salvage chemotherapy. Only a minority (11% in our study) of relapses, however, are potentially suitable for this approach.

Disclosures
Mollee: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees.