Abstract
Purpose:We have developed a novel DC population differentiated from human monocytes in the presence of GM-CSF and IFN-alpha (IFN-DC), which is highly efficient in internalizing tumour cell antigens and in the cross-priming of CD8+T cells, promoting efficient anti-lymphoma response. Preclinical results prompted us to start a clinical trial of IFN-DC combined with low-dose Rituximab(RTX) in patients with Follicular lymphoma (FL), which is an indolent, immune-responsive, but still incurable cancer.
Patients and Methods: In October 2014 we started a phase I clinical trial (EudraCT: 2013-003158-25) testing safety, immunogenicity and systemic clinical responses of low-dose RTX combined with autologous IFN-DC, administered by intra-nodal injections. Patients features: age 18-75y, indolent FL, relapsed or refractory (R/R), stage III-IV low tumour burden, with at least 1 superficial pathologic lymph node. One leukapheresis was scheduled at study entry for harvesting mononuclear cells. Eight cycles of RTX (5-20mg) and IFN-DC (30±10x106) were planned: the first 4 every two weeks, followed by other 4 cycles administered monthly. All injections were delivered with the aid of an ultrasound guide. Blood test for immune-responses and autoimmunity markers were scheduled at 0,+72d, +132 days ; +9; +18;+24 months.
Results: as of the 31st July 2018, 8 patients have completed treatment and have been evaluated for response (median follow-up=24 months; range=8-45 mo). Median age of the study population was 60 years (range 27-76). All subjects had disseminated disease and enlarged lymph nodes or lesions greater than 1.5 cm at multiple sites available for local injections and monitoring for distant response. All patients were R/R after previous systemic therapy (median lines=2, range1-4) and 3/8 (37.5%) after auto-transplantation. The treatment was very well tolerated and manageable. No relevant adverse events were observed. Four out of 8 (50%) patients had objective response (OR) with 3/8(37.5%) attaining complete remission (CR); 2/8 (25%) are in stable disease at +8 and +25 months; 2/8 (25%), who did not achieve OR, progressed at +8 and +14 respectively. One patient progressed 4 months after achieving CR (Figure1). In all patients who achieved OR or who are in stable disease, induction of a tumour specific immune response was observed.
Conclusions: local RTX and IFN-DC combined therapy was effective in eliciting in 50% of R/R FL with low tumour burden systemic and durable responses, which were associated with induction of specific anti-FL T cell responses.
No relevant conflicts of interest to declare.
