Improved Quality of Life with Interleukin-6 (IL-6) Blockade with Siltuximab Peri-Autologous Hematopoietic Stem Cell Transplantation (AHCT) in Older Patients with Multiple Myeloma (MM)

Abstract

Background Symptom burden after AHCT for multiple myeloma is highest at count nadir with elevation of inflammatory markers such as IL-6 as one potential etiology (Wang, 2014). We aimed to alleviate symptom burden post-AHCT using siltuximab (anti-IL-6 antibody, EUSA Pharma) in older MM pts. Methods Siltuximab at 11mg/kg was given on day -7 and day +21 from AHCT. Patient reported outcomes were assessed using the MD Anderson Symptom Inventory (MDASI) – MM at baseline, day -2, +7, and +30. C-reactive protein (CRP) and IL-6 were measured at baseline, day -2, 0, +3, +7, +14, +21, and +30. IL-6 was quantitated with the Proteinsimple Ella platform. Results Between 1/2018 – 8/2019, the study enrolled 14 pts, passed the interim analysis for futility, and enrolled an additional 14 pts. Median age for all 28 pts was 66 (range 60-74) with 57% female and 64% Caucasian. Median HCT-CI was 2 (range 0-8, with HCT-CI >2 in 13 pts) and median KPS on day -2 was 80 (range 70-90) with 75% receiving 200mg/m2 of melphalan. Neutrophil engraftment occurred at a median of 10 days (range 8-12); 11 pts (19%) received at least one dose of filgrastim after engraftment. 2/28 had neutropenic fever with one having a true bacteremia and CMV reactivation. One pt developed a pneumonia requiring high-flow oxygen without a fever. The average MDASI-MM score per question at each time point ranged between 0-3 on a scale of 1-10, which represents an improvement from a historical control group where scores peaked at day 11 after AHCT with average scores up to 8 (Figure 1). CRP levels were detectable at baseline in 23/28 (82%, Figure 2). Median CRP levels at each time point were 0.19mg/dL (range IL-6 level analysis is ongoing (Figure 3). Median IL-6 levels (n=23) at each time point were 4 pg/mL (range Two pts had mild first dose siltuximab infusion reactions, one with tingling of lips and one with hives that resolved with Benadryl. Neither had a reaction with the subsequent infusion. With the 2nd dose, one pt had rigors and angioedema which resolved with discontinuing the infusion and anti-reaction medications. Conclusion We show for the first time that IL-6 blockade with siltuximab is feasible and safe post-AHCT, and it mitigates IL-6 elevation in most pts with an associated improvement in symptom burden and quality of life.