Chronic graft vs. host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Chronic GVHD (cGVHD) has many similarities to de novo autoimmune disorders. While the presence and association of autoantibodies is well reported in these disorders, their role and clinical use remains a less studied area after SCT. We report the presence of autoantibodies in SCT recipients and a possible association with presence of cGVHD. During routine follow-up visits peripheral blood samples were tested for: rheumatoid factor (RF), antinuclear antibody (ANA), double stranded DNA (dsDNA), antimitochondrial antibody, antismooth muscle antibody (Anti Sm), antiendomysial, antireticulin antibodies, antithyroid peroxidase antibodies and an extractable nuclear antigen screen, in 13 SCT recipients. Six of 13 (46%) patients had one or more autoantibodies. All the patients with antibodies had cGVHD where as none of the patients without cGVHD had any autoantibodies (P = 0.025). Three (23%) patients had only one autoantibody and three (23%) of them had more than one autoantibody. ANA was positive in three (23.3%) patients, double stranded DNA in four (30.7%) patients, RF in one (7.6%) and Anti Sm muscle in two (15.3%) patients. In the present study, autoantibodies were detected predominantly in patients with presence of cGVHD. They also appeared to be more frequent in an unmanipulated graft and so less in patients with a T-cell depleted allograft. In two of 13 patients only there appeared to be an association between the antibody titre and flare up in skin symptoms. In conclusion, this small series raises interesting questions about the presence and role of autoantibodies after SCT and their association with cGVHD.
Background: VTd is considered a standard of care for patients with newly diagnosed multiple myeloma (NDMM) who are transplant eligible. The CD38-targeted monoclonal antibody daratumumab (DARA) demonstrated a significant reduction in the risk of progression or death and improvement in stringent complete response (sCR), CR or better (CR), and minimal residual disease (MRD)-negative rates when added to VTd in transplant-eligible NDMM patients in the phase 3 CASSIOPEIA study. Aims: Determine MRD status and its association with progression-free survival (PFS) in transplant-eligible NDMM patients receiving D-VTd versus VTd as pre-transplant induction and post-transplant consolidation in CASSIOPEIA. Methods: Transplant-eligible NDMM patients were randomized 1:1 to 4 cycles of pre-autologous stem-cell transplant (ASCT) induction and 2 cycles of post-ASCT consolidation with DARA + VTd or VTd. Analyses of MRD were performed on bone marrow aspirates after induction and after consolidation (at Day 100 post-ASCT) for all patients, regardless of response. MRD was assessed primarily by EuroFlow-based multiparametric flow cytometry (MFC) and, based on sample yield, secondarily with next-generation sequencing (NGS; Adaptive clonoSEQ â Assay).Here, we report post-induction and post-consolidation MFC results (10 -5 sensitivity threshold) and post-consolidation NGS results (10 -6 ). Results: A cohort of 1,085 patients received D-VTd (n = 543) or VTd (n = 542). The post-induction MRD-negative rate (MFC, 10 -5 ) was significantly higher for the D-VTd arm versus the VTd arm (34.6% vs 23.1%; P < 0.0001; Table ). Similarly, post-consolidation MRD-negative rates by MFC (10 -5 ) and NGS (10 -6 ) were significantly higher for patients receiving D-VTd versus VTd (63.7% vs 43.5% and 39.1% vs 22.8%, respectively; P < 0.0001 for both analyses; Table ). Post-consolidation MRD-negative rates (MFC, 10 -5 ) were consistent across patient subgroups, including ISS stage III or high-risk cytogenetics. Multivariate analyses accounting for treatment arm and MRD negativity (MFC) showed a PFS benefit in patients reaching MRD negativity (HR, 0.31; 95% CI, 0.20-0.50; P < 0.0001), and D-VTd showed additional PFS benefit versus VTd alone (HR, 0.48; 95% CI, 0.30-0.78; P = 0.0028). Analysis of MRD based on response (per IMWG criteria) will be presented.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.