ICOSL vIgD

A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants further clinical study for the treatment and/or prevention of GVHD.

A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants further clinical study for the treatment and/or prevention of GVHD.

A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants further clinical study for the treatment and/or prevention of GVHD.

A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants further clinical study for the treatment and/or prevention of GVHD.

A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants further clinical study for the treatment and/or prevention of GVHD.