Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702

Abstract

International Myeloma Working Group (IMWG) response criteria for multiple myeloma (MM) currently involve a combination of blood-based, urine-based, and marrow-based assessments [1]. Unlike blood-based assays which can be obtained from a single venipuncture, urine testing in MM requires that every urinary void over a 24-h period be collected. Collecting and storing all urinary voids can be difficult for patients with underlying frailty, treatment-related neuropathy, or unreliable access to refrigeration [2, 3]. Additionally, fewer than 1% of patients with plasma cell disorders have Bence-Jones proteinuria quantifiable on urine protein electrophoresis (UPEP) in the absence of abnormalities on serum protein electrophoresis (SPEP), serum immunofixation (SIFE), or serum free light chain (SFLC) testing [4]. In the real-world setting, fewer than a third of patients with MM undergo 24-h UPEP testing at diagnosis [5]. Several post hoc analyses of Phase 3 trials have demonstrated that the prognostic impact of 24-h urine immunofixation (UIFE) on progression-free survival (PFS) is negligible compared to that of SFLC assays or bone marrow plasma cell burden [6, 7].

The broader practicality of removing urine assessments from response criteria entirely has only been investigated once to our knowledge (Table 1) [3]. Adopting urine-free criteria led to changes in response depths for only 4% of patients in this small single-center analysis; however, the impact of these changes on PFS was not evaluated. To answer this more important question, we conducted an unplanned post hoc analysis of patients with MM enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0702 (STaMINA) trial of treatment strategies following autologous stem cell transplantation (ASCT) (clinicaltrials.gov ID: NCT01109004). This trial demonstrated no intent-to-treat differences in PFS or overall survival between standard maintenance, post-ASCT consolidation, and tandem transplantation [8]. We pooled patient data from all study arms, including patients who did not complete their planned treatment strategies. We analyzed responses at the Day +56 timepoint following ASCT (first ASCT if patients underwent tandem transplantation), which was the first timepoint for response assessments. Patients who were non-evaluable for urine-free responses (as defined below) or who had progressive disease (PD) at this initial timepoint were excluded. Response assessments relative to diagnosis were calculated as stable disease (SD), partial response (PR), very good partial response (VGPR), or complete response (CR) [1]. To simplify comparisons, minimal responses were classified as SD and stringent complete responses as CR.

Table 1 Schema of traditional versus urine-free response criteria.

Full size table