Tocilizumab for CRS Prophylaxis in Haploidentical Peripheral Stem Cell Transplantation

Introduction The use of anti IL-6 therapy in the management of cytokine release syndrome (CRS) is well defined in the setting of chimeric antigen receptor T-cell (CAR-T) therapy, however its use in haploidentical peripheral blood stem cell transplants (haploPBSCT) remains unclear. Prophylaxis with the anti IL-6 monoclonal antibody tocilizumab is thought to improve rates of CRS after infusion and activation of alloreactive T cells. We sought to evaluate the effects of prophylactic anti IL-6 blockade with tocilizumab on the rates of CRS in patients with haploPBCST. Methods Patients age >18 years of age who underwent a CD3+ T cell replete haploPBSCT with standard GVHD prophylaxis and post-transplant prophylactic tocilizumab on day +1 at dose of 4mg/kg were included. Patients were evaluated for CRS according to previously published criteria by Lee et. al. Primary outcome was incidence and severity of CRS, additional outcomes included neutrophil and platelet engraftment, incidence of acute GVHD (aGVHD), treatment related mortality (TRM) and overall survival (OS). Results Ninety-one patients met inclusion criteria, 78 patients received tocilizumab prophylaxis. CRS rates of entire cohort were 46% for any grade CRS and 2% severe grade (3+) CRS. Patients who received tocilizumab were less likely to have any grade (43% vs 63%) and mild grade (42% vs 54%) CRS when compared to patients who did not receive prophylactic tocilizumab. The highest grade of CRS in patients receiving tocilizumab was grade 3 with the majority (57% vs 39%) having no grade CRS compared to those who did not receive prophylaxis. One grade 5 event occurred in patients who did not receive tocilizumab. Onset of CRS occurred later in patients who received tocilizumab (median day +2, range 1-14) compared to those who did not. Neutrophil and platelet engraftment occurred later in patients who received tocilizumab (day +21 and day +32) compared to those without prophylaxis (day 17.5 and day +24.5). Earlier incidence of aGVHD was seen in patients who received tocilizumab (day +38 vs day +30) though did not have effect on 1-year TRM (34% vs 31%). Median OS of patients who received tocilizumab prophylaxis was 15 mos. Conclusion Patients who received tocilizumab prophylaxis on day +1 after haploPBSCT appeared to have improved rates of lower grade CRS when compared to patients who did not receive prophylaxis. Furthermore, tocilizumab was well tolerated and appeared to improve the rates of mild (grade 1-2) CRS when compared to patients who did not receive prophylaxis, though not at statistical significance. Additional investigations into the effects of prophylactic tocilizumab in haploPBSCT and rates of chronic GVHD are planned.