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• W2914193276 abstract "IntroductionHigh dose melphalan with autologous stem cell transplantation (ASCT) is a therapy mainstay in multiple myeloma (MM). However, the median PFS after ASCT is under 5 years even with contemporary agents. This may be due to immune dysfunction after ASCT. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) reconstitute rapidly after ASCT, can inhibit antitumor immune responses, and are a target for non-cross-resistant therapy in the MRD-positive state.MethodsWe conducted a randomized pilot study to evaluate 2 methods of Treg depletion in MM patients undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 mAb (basiliximab 20 mg IV) was given day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. In the ex vivo Treg depletion (EVTRD) arm, CD4+CD25+ Tregs were depleted from ASC grafts with anti-CD25 microbeads and CliniMACS device (Miltenyi). Primary endpoints were: 1) evaluate efficiency of Treg depletion, 2) measure kinetics of Treg depletion and recovery and 3) determine toxicities with the two methods of Treg depletion. Secondary endpoints were engraftment rates and disease response.ResultsFifteen patients were enrolled, 5 in each arm. One patient in the IVTRD arm was removed from study due to mobilization failure. ASC were collected following filgrastim/plerixafor. The conditioning regimen consisted of melphalan 200 mg/m2. All patients engrafted; median times to neutrophil/platelet engraftment were similar between arms. 4/5 patients in the EVTRD arm had neutropenic fever (vs 2/5 in control ASCT arm and 2/4 in IVTRD arm). Engraftment syndrome occurred in 1 patient in the EVTRD arm.ConclusionMedian ex vivo depletion of CD4+CD25+ Tregs from 5 ASC grafts was 93% (figure 1). Baseline frequencies of peripheral blood (PB) CD4+FoxP3+ Tregs were similar between all arms (p=NS). A reduction in Treg frequency was seen in the EVTRD arm compared to controls at day +14 (p=0.0001) and +21 (p=0.025, figure 2). The IVTRD arm had lower Treg frequency at day +28 compared to controls (p=0.053). These data suggest that in vivo and ex vivo Treg depletion are feasible and result in significant reduction and delay in Treg recovery post-ASCT for MM. These methods could serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes. High dose melphalan with autologous stem cell transplantation (ASCT) is a therapy mainstay in multiple myeloma (MM). However, the median PFS after ASCT is under 5 years even with contemporary agents. This may be due to immune dysfunction after ASCT. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) reconstitute rapidly after ASCT, can inhibit antitumor immune responses, and are a target for non-cross-resistant therapy in the MRD-positive state. We conducted a randomized pilot study to evaluate 2 methods of Treg depletion in MM patients undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 mAb (basiliximab 20 mg IV) was given day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. In the ex vivo Treg depletion (EVTRD) arm, CD4+CD25+ Tregs were depleted from ASC grafts with anti-CD25 microbeads and CliniMACS device (Miltenyi). Primary endpoints were: 1) evaluate efficiency of Treg depletion, 2) measure kinetics of Treg depletion and recovery and 3) determine toxicities with the two methods of Treg depletion. Secondary endpoints were engraftment rates and disease response. Fifteen patients were enrolled, 5 in each arm. One patient in the IVTRD arm was removed from study due to mobilization failure. ASC were collected following filgrastim/plerixafor. The conditioning regimen consisted of melphalan 200 mg/m2. All patients engrafted; median times to neutrophil/platelet engraftment were similar between arms. 4/5 patients in the EVTRD arm had neutropenic fever (vs 2/5 in control ASCT arm and 2/4 in IVTRD arm). Engraftment syndrome occurred in 1 patient in the EVTRD arm. Median ex vivo depletion of CD4+CD25+ Tregs from 5 ASC grafts was 93% (figure 1). Baseline frequencies of peripheral blood (PB) CD4+FoxP3+ Tregs were similar between all arms (p=NS). A reduction in Treg frequency was seen in the EVTRD arm compared to controls at day +14 (p=0.0001) and +21 (p=0.025, figure 2). The IVTRD arm had lower Treg frequency at day +28 compared to controls (p=0.053). These data suggest that in vivo and ex vivo Treg depletion are feasible and result in significant reduction and delay in Treg recovery post-ASCT for MM. These methods could serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes." @default.
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• W2914193276 title "Pilot Study of Regulatory T-Cell Depletion in the Setting of Autologous Stem Cell Transplantation for Multiple Myeloma" @default.
• W2914193276 doi "https://doi.org/10.1016/j.bbmt.2018.12.822" @default.
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