P-070: Failure to Clear Circulating Tumor Cells After One Week of Daratumumab, Bortezomib and Dexamethasone is Associated with a Reduced Progression-Free Survival for Myeloma Patients

Introduction: Obtaining bone marrow MRD negativity after induction therapy is associated with a superior PFS and OS. Conversely, patients with a high level of circulating tumor cells (CTC) in the peripheral blood prior to commencing front-line therapy have inferior outcomes. Less is known about the impact of CTC level at relapse, and the implications of early changes in CTC levels are not known. In Australia, Bortezomib, Daratumumab and Dexamethasone (BDd) is only available as 2nd line therapy, hence almost all patients receive this combination making them a group who are treated homogeneously and are highly representative of MM patients. We hypothesized that CTC level and their early changes would predict long term outcome in MM patients receiving BDd at 2nd line.

Methods: Patients receiving BDd at second line were identified. Peripheral blood was collected prior to therapy and on day 8. Blood was analyzed within 24 hours using the Euroflow next-generation flow cytometry platform and the Infinocyte CTC analysis database.

Results: 28 patients have been analysed with a median follow-up of 232 days (range 46-722). The median limit of detection was 0.00035%, and the median limit of quantification was 0.00081%. CTC were detectable prior to treatment in 27/28 patients (median value 0.0087%, range 0.00081-6.8%). CTC were detectable in 10/28 on Day 8 of cycle 1 (median value 0.0054%, range 0.00028 – 0.33%).

There were no differences in age, sex or prior Bortezomib exposure between those who cleared CTC by day 8 and those who did not. Failure to clear CTC was associated with an increased incidence of high risk FISH (50% vs 17%) and gain 1q (50% vs 28%), increased exposure to prior Lenalidomide (60% vs 23%), and a shorter median time from diagnosis (835 vs 1239 days) when compared with those who cleared CTC.

Patients who had higher levels of CTC prior to commencing second line (>0.01%) had a shorter PFS than those who did not (median PFS 400 days vs not reached, p=0.0482). The failure to clear CTC by day 8 had a strong correlation with PFS. Patients who failed to clear had a median PFS of 359 days whilst median PFS is not yet reached for those who cleared CTC (p=0.0194).

Conclusions: This data suggests that failure to clear CTC from the blood within one week of second line BDd predicts patients who are destined for brief remissions. This can be achieved without the need for invasive bone marrow biopsies. Early identification of patients who will have short remissions could allow for a trial of early intensification of therapy to improve outcomes.