Re-challenging with anti-CD38 monotherapy in triple-refractory multiple myeloma patients is a feasible and safe approach

Multiple Myeloma patients refractory to both proteasome inhibitors and immuno-modulatory drugs have poor prognoses, with median overall survival estimates of 9. We present data from two patients with MM in disease progression on ongoing treatment; both had received Daratumumab (Dara) as monotherapy earlier and were re-challenged with Dara on relapse. Bone Marrow and blood samples were collected before start of treatment and the later before administration of each dose. Detailed analyses of circulating cell populations were performed. We demonstrate that Dara had durable single-agent activity on re-treatment in both patients while both patients had no effective treatment options. As expected, we show that following initial Dara treatment, MM cells at relapse retained high levels of CD38 expression. Dara treatment depletes circulating NK cells almost immediately after the start of the treatment. Furthermore, both NK cells and CD8+ populations were partially increased at treatment interruption. Anti-inflammatory myelomonocytic cells showed a sharp decrease at the same time. These data strongly suggest that continuous treatment with Dara decreases ADCC mediated antitumor activity using two independent mechanisms, which can both be recovered by a short treatment interruption. In line with this, maintenance treatment should include an intermittent treatment regime with appropriate time for recovery. Figure 1. Figure 1. Disclosures Off Label Use: In this study Daratumumab was used in a compassionate use program provided by Janssen.. Ahmadi:Janssen: Employment. Khan:Janssen: Employment. Nahi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.