Pilot Study Using Changes in Serum BCMA to Determine Disease Progression in Multiple Myeloma

In recent years, new and more effective drugs have become available for the treatment of multiple myeloma (MM), resulting in a dramatic increase in median overall survival (OS).1 Therapeutic options have expanded to include immune-based approaches such as daratumumab and elotuzumab.2 The clinical course of MM is highly variable, and relapsing/refractory (RR)MM more so, with periods of response followed by periods of relapse. Improvements in predicting and determining individual patient outcome would allow for more effective and timely treatment interventions.

Over the last several years, we have identified a new serum biomarker, B cell maturation antigen (BCMA), for monitoring patients with MM. Changes in serum (s)BCMA quickly identify changes in the clinical status of MM and it is also a promising new prognostic marker. Specifically, we demonstrated that compared to healthy donors, patients with MM showed elevated levels of sBCMA.3 These levels were positively correlated with the proportion of plasma cells in bone marrow biopsies and changes in monoclonal (M)-protein and serum free light chain (SFLC) levels and indicated a patient's current clinical status.3 Importantly, sBCMA levels were also independent of renal function and maintained independent significance when tested against other known prognostic markers for MM including age, serum β-2-microglobulin, hemoglobin, and presence of bone disease. Furthermore, we demonstrated that increases in sBCMA by \> 25% from start of any new therapy predicted a markedly shorter progression free survival (PFS) and occurred much more quickly than those observed with standard biomarkers to monitor the course of MM including M-protein and SFLC levels.

To further validate sBCMA as a disease status biomarker for MM, we have incorporated monitoring of sBCMA for all patients participating in several ongoing clinical trials. Specifically, patients participating in a Phase 1 study of ruxolitinib, methylprednisolone and lenalidomide for RRMM patients, were monitored weekly for sBCMA and standard MM markers during their first treatment cycle and monthly thereafter. We determined the safety and efficacy of this novel, all oral combination consisting of the Janus kinase 1/2 inhibitor ruxolitinib in combination with lenalidomide and methylprednisolone.5 Successive cohorts of participants (3 participants per cohort) were given the following doses of drugs, all oral (PO): Dose Level 0: ruxolitinib 5 mg twice a day (BID), methylprednisolone 40 mg every other day (QOD) and lenalidomide 5 mg daily (QD) on days 1-21 of a 28-day cycle; Dose Level 1: ruxolitinib 10 mg BID, methylprednisolone 40 mg QOD, and lenalidomide 5 mg QD on days 1 21 of a 28-day cycle; Dose Level 2: ruxolitinib 15 mg BID, methylprednisolone 40 mg QOD, and lenalidomide 5 mg QD on days 1 21 of a 28-day cycle), and Dose Level 3: ruxolitinib 15 mg BID, methylprednisolone 40 mg QOD and lenalidomide 10 mg QD on days 1 21 of a 28-day cycle. Dose Level 3 was the maximum administered dose.