IMMU-27. Re-MATCH PROTOCOL: PHASE I STUDY OF AUTOLOGOUS TUMOR SPECIFIC LYMPHOCYTE TRANSFER (ALT) + DC VACCINE (DCV) DURING RECOVERY FROM MYELOABLATIVE CHEMOTHERAPY (MAC) AND AUTOLOGOUS STEM CELL RESCUE (HDC + ASCR) OR NON-MYELOABLATIVE CHEMOTHERAPY (NMAC) IN PATIENTS WITH RECURRENT CENTRAL PNETs (r-PNET). Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Gururangan, Sridharan; Grant, Gerald; Driscoll, Tim; Archer, Gerald; Herndon, James; Friedman, Henry; Kurtzberg, Joanne; Bigner, Darell; Sampson, John; Mitchell, Duane
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i104
• Page End: i104
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.343
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: We performed a phase I study to assess feasibility, safety, and efficacy of ALT+DCV following HDC +ASCR (group A) or NMAC (group B) in pts with r-PNET. METHODS: Eligible pts underwent surgery to confirm diagnosis and obtain tumor for vaccine preparation. Pts with local (group A) or metastatic (group B) recurrence received 4 cycles of cytoreductive chemotherapy prior to either MAC (carboplatin + thiotepa + etoposide) (group A) or NMAC (cyclophosphamide + Fludarabine) (group B). Two dose levels of ALT were evaluated [3 x 10 6 or 3 x 10 7 cells/kg] with 3 intradermal biweekly DCVs (10 7 cells each). Safety evaluation for DLT assessment was 2 weeks past third DCV with monthly vaccines thereafter as available. Correlative studies for immune response included TCR sequencing and measurement of serum cytokines RESULTS: Ten pts (M5; F5) were treated on protocol (group A 1, group B 9). Nine evaluable pts received immunotherapy; DCV [median 3 doses (3-9)] + ALT [3 x10 6 /kg (n=4) or 3 x 10 7 /kg (n=5)]. There were no DLTs observed. At median of 21 months follow-up, 3 pts are alive with (n=2) or without (n=1) disease 33-42 months following treatment. TCR RNA sequencing demonstrates massive clonal expansion of T cells following ALT+DCV and positive correlation with clinical outcomes. Persistence of tumor-reactive (IFN-gamma secreting) T cell clones in the peripheral blood was observed 4 months after treatment in a patient with long-term disease control. CONCLUSIONS: ALT+DCV is feasible, safe, and shows signs of biologic and clinical activity in some pts with r-PNET.