Low Dose IL-2 or Low Dose IL-2 Combined With IFN
➤ ➤ There is limited to no role for low dose IL-2 as a single agent, with the
possible exception of patients with impaired organ function. (B based on
a prospective, uncontrolled trial)
➤ ➤ Efficacy data favor HD IL-2 compared to low dose IL-2. (A)
Note: Investigation of low dose regimens in conjunction with new
immunotherapies is a research consideration, given that checkpoint inhibitors
are being studied at much lower doses in combination than those used in the
original single agent trials. Alternative schedules should also be explored in
the context of combination immunotherapy or immunotherapy with targeted
agents. (B)
HD IL-2 as Second-Line Therapy (A)
A er An -VEGF TKI
➤ ➤ Following initial anti-VEGF TKI, anti-PD-1 agents are the preferred second-
line immunotherapy. (67%)
Note: This is based on the logistics of outpatient anti-PD-1 therapy and the
less stringent eligibility criteria, rather than being a comparison with other
immunotherapy agents.
➤ ➤ If anti-PD-1 agents are not available, HD IL-2 should be considered as
second-line therapy after a washout period, in appropriate patients (C).
Note: Patients should be evaluated carefully with a cardiac echo and show
adequate cardiac function prior to initiation of IL-2 therapy.
A er an -PD-1 Therapy (C)
➤ ➤ HD IL-2 could be used after anti-PD-1 therapy based on the lower risk of
persistent immune-related adverse events with anti-PD-1 agents compared
with other checkpoint inhibitors (e.g., anti-CTLA-4 agents). (73%)
Note: The scientific rationale for this therapeutic sequence is based on
the different, potentially synergstic, mechanisms of action of HD IL-2 and
anti-PD-1 therapy.
Summary of HD IL-2 Recommenda on
➤ ➤ Eligible patients (clear cell histology with adequate organ reserve after
nephrectomy, with few adverse risk features) should be considered for IL-2
therapy at centers with adequate experience.
