8535 Background: Viral oncolytic therapy with intravenous Pelareorep, the infusible form of reovirus, is supported by preclinical data indicating that its antitumor activity results from direct cytolysis and an immune response against infected MM cells. Our preclinical data has shown that monocytes serve as carriers of reovirus from the peripheral blood to the bone marrow (Dona et al, ASH, 2019). In this abstract we present patients treated to date that were Carfilzomib refractory at enrollment. Methods: Pelareorep (P), Carfilzomib (K), and dexamethasone (d) were all infused on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Patients were pretreated with dexamethasone 20 mg intravenously, then Carfilzomib 20 mg/m2 on days 1 and 2 of cycle 1, and 56 mg/m2 thereafter. Pelareorep dose levels were at 3x1010, 4.5*1010, and planned 9*1010 median tissue culture infectious dose (TCID50). Results: All 6 evaluable patients showed reovirus infection in the post-treatment marrow aspirates cycle 1 day 9. Despite all patients having Carfilzomib-refractory disease, 2 patients achieved partial responses, two patients with short duration stable disease but few side effects, and 2 patients with PD. Of the two responders, one patient developed fever and grade 4 thrombocytopenia during cycle 1 and withdrew mid cycle. The other patient with a PR developed a cytokine storm - this patient presented cycle 1 day 3 hypoxemic with pneumonia, systolic failure (LVEF 69%-- > 26%), with biochemical evidence of hemophagocytic syndrome with elevated IL-2R, IL-6, and ferritin > 25K. This patient responded to tocilizumab, but ultimately died two weeks later with sepsis. Autopsy revealed pneumonia, no areas of reovirus infection other than in myeloma cells, and reovirus productive infection in 5-35% of myeloma cells (i.e. capsid protein). Conclusions: While infection of myeloma cells was seen in all evaluable patients on cycle 1 day 9, those with a clinical response demonstrated concomitant CD8 & NK cell recruitment, PD L1 upregulation, activated caspase-3 expression, increased viral protein production within the myeloma cells, and these patients demonstrated mild to severe signs and symptoms consistent with secondary HLH. This is the first report of cytokine storm after oncolytic virus in a patient with a blood cancer, a syndrome thought to be related to T-cell activation from the combination treatment. This trial was supported by the NCI Division of Cancer Treatment & Diagnosis Cancer Therapy Evaluation Program (CTEP). Clinical trial information: NCT02101944 .
Hemoadsorption Treatment with CytoSorb® in Probable Hemophagocytic Lymphohistiocytosis: A Role as Adjunctive Therapy?
