Table 2:

TTS 2019 Consensus and the authors’ proposed treatment approaches, based on expert opinion (ungraded practice recommendations).

2019 Consensus	DSA	Banff 2017 phenotypes	SOC	Consider adjunctive therapies
Early acute (<30 days)	Preexisting DSA (or nonimmunologicaly naïve)	Active AMR	• Plasmapheresis/IVIGa • Steroids	• Complement inhibitors • Rituximab • Splenectomy
Late (>30 days)	Preexisting DSA	Active AMR	• Plasmapheresis/IVIGa • Steroids	• Rituximab
		Chronic AMR	• Optimize baseline immunosuppressionb
	De novo DSA	Active AMR	• Optimize baseline immunosuppressionb • Evaluate and manage non-adherence	• Plasmapheresis, IVIG • Rituximab
		Chronic AMR		• IVIG
Authors’ proposal	DSA	Banff 2022 phenotypes	Primary treatment	Consider adjunctive therapies
			General considerations:
			Consider the following when deciding on the type and intensity of treatment: • Severity and acuity of graft dysfunction (e.g. activity index): May determine the intensity of the chosen treatment. • Level of chronic injury at the time of biopsy(chronicity index): this helps exclude unmodifiable chronic damage. • Presence of comorbidities: Avoids increased risks associated with over-immunosuppression. • Recipient age: Presumably, elderly patients derive less benefit. • If concomitant TCMR is diagnosed, also treatment with corticosteroids, ATG, or alemtuzumab should be considered. • Consider follow-up biopsies for early detection of phenotype transition (e.g. transition to active AMR after a diagnosis of probable or of probable AMR) or for treatment monitoring.
Early (<6 months)	Preexisting (and/or de novo) DSA	Active AMR (chronic-active AMR)	• Apheresis (Plasmapheresis or immunoadsorption) with or without IVIGc • Optimize baseline immunosuppressionb	• CD38 antibodyd • Complement inhibitione
		Probable AMR	• Optimize baseline immunosuppressionb	• CD38 antibodyd
	No DSA	MVI, C4d-/DSA-negative	• Optimize baseline immunosuppressionb	• CD38 antibodyd
Late (>6 months)	De novo (and/or preexisting) DSA	Active/chronic-active AMR	• Optimize baseline immunosuppressionb • CD38 antibodyd
		Chronic AMR	• Optimize baseline immunosuppressionb
		Probable AMR	• Optimize baseline immunosuppressionb	• CD38 antibodyd
	No DSA	MVI, C4d-/DSA-negative	• Optimize baseline immunosuppressionb,f	• CD38 antibodyd

ATG, antithymocyte globulin; PP, plasmapheresis.

^aDaily or alternate day plasmapheresis sessions × 6 based on DSA titer; IVIG 100 mg/kg after each plasmapheresis treatment or IVIG 2/kg at end of plasmapheresis treatments

^bIncludes the use of tacrolimus with goal through levels of >5 ng/ml and use of maintenance steroid equivalent to prednisone 5 mg/day.

^cWe suggest apheresis treatment courses over 2–3 weeks, starting with three daily treatments, followed by sessions every 2–3 days. Optionally, high-dose IVIG (2 g/kg) may be administered at the end of the apheresis course.

^dCD38 targeting may include the use of daratumumab at 16 mg/kg; weekly over 1 month (pretreatment before the first two administrations to prevent first dose reactions), followed by monthly doses until months 3–6. The duration of treatment may be guided by dd-cfDNA monitoring and/or follow-up biopsy results.

^eComplement inhibition may include the administration of one or more doses of eculizumab.

^fIn DSA- and C4d-negative MVI, a switch from mycophenolic acid to an mTOR inhibitor may be considered for optimization of maintenance immunosuppression.