Experimental Pharmaceuticals for Steroid-Refractory Acute Graft-versus-Host Disease

Figures & data

Table 1 Conventional Second-Line Therapies for SR-aGVHD

Agent	Evidence	CR Rate	Toxicities	Survival
Sirolimus	PhaseI^Citation42 Retrospective^Citation13	24% 42%	TMA	1-yr: 44%
Mycophenolate Mofetil	Retrospective^Citation14	26%	Myelosuppression	3-yr: 40%
Pentostatin	PhaseI^Citation43 Retrospective^Citation16	63% 18%	Late Infection	1-yr: 30% 18-mo: 21%
Anti-thymocyte globulin	Phase II^Citation44 Retrospective^Citation15	32% 20%	Infection	6-mo: 45% 1-yr: 32%
Infliximab	Retrospective^Citation17	17%	Infection	12-week: 33%
Tocilizumab	Retrospective^Citation45	40%	Transaminitis Infection	>1yr: 27%
Inolimomab	Retrospective	38%	Infection	1-yr: 30%
Extracorporeal Photopheresis	Retrospective^Citation46 Phase III^Citation28	54% 20%		3-yr: 50%

Figure 1 Proposed novel agent mechanisms.

Table 2 Ruxolitinib in SR-aGVHD. BAT: Best Available Therapy (Sirolimus, MMF, MSC, MTX, Infliximab, ECP, Etanercept, ATG)

		ORR	Toxicities	Survival
Retrospective^Citation25		Best: 81.5% (46% CR)	Cytopenia Infection	6-mo: 79%
REACH1^Citation27	Phase II	Day 28: 54.9% (27% CR) Best: 73.2% (56% CR)	Cytopenia Edema	6-mo: 51%
REACH2^Citation28	Phase III	Rux: Day 28: 62% (34% CR) BAT: Day 28: 39% (19% CR)		Rux: 1-yr: 49% BAT: 1-yr: 44%

Table 3 Active Trials in SR-aGVHD

	Response	Phase	Intervention
Itacitinib	70.6% (30% CR)	Phase I	Itacitinib+Tocilizumab	NCT04070781
CD3/CD7-IT	60%(50% CR)	Phase II	CD3/CD7-IT vs Ruxolitinib	NCT00640497
Neihulizumab	Skin only: 91%	Phase I	Neihilizumab	NCT03327857
FMT	Up to 100%	Phase II	FMT in GI aGVHD	NCT04059757

Abbreviation: FMT, fecal microbiota transplant.

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