Apavac, a Simple Autologous Vaccination Process (AV) Associated with Clinical Efficacy in 56 Patients (pts) Having Cancer (C) and 11 Pts Having Hematological Malignancies (HM)

Introduction. Nowadays, immune therapy is a major therapy for C. Vaccination was developed for more than 20 years (y) with less than 20% of responses (R) associated with a mild advantage in overall survival (OS) in addition to its complexity. APAVAC is an AV consisting of hydroxyapatite ceramic powder (HA) and specific tumor proteins purified from the C or from the serum (S). HA is aimed to purify and vectorize C proteins containing heat shock proteins and C antigens (Ag). So, AV associates an adjuvant, HA, and autologous C Ag. A randomized, placebo-controlled, double-blind chemo-APAVAC clinical trial in pet dog model of diffuse large B-cell lymphoma (L) showed significant OS for the APAVAC arm (Marconato L et al. Clin Cancer Res 2013).

Patients. 67 pts (30 males and 37 females) were included in this pilot study. All of these pts had advanced disease (D), in relapse or in refractory relapse. AV was weekly administered by sc for 1 mo followed by monthly injection for at least 4 mo. Pts received at least 1 AV. Evaluation included R rate; OS was calculated from the beginning of the AV.

Results.The median age was 65y (range:14-85). 31 pts received an incomplete cycle of AV. 16 of them have ongoing therapy. Among the whole population, 14 pts died with 5 due to associated therapy and 9 early deaths directly due to the D. 36 pts received a complete cycle of AV (at least 8 injections) with follow-up >6 months (mo). Tolerance was excellent, with only mild local inflammation or pain, controlled by lidocaine patch. No auto-immune manifestations were observed. Among the 36 pts having a complete cycle of AV, 11 had AV from the C and 25 from the S.

33 of them had solid C, including 10 glioblastoma grade IV with 8 having 3 previous lines of therapy (PLT) and 2 having 1 PLT; 6 had Progressive D (PD) and 4, Stable D (SD) at the inclusion followed by 5 SD and 5 PD, all of them with a median OS of 12 mo; 1 bladder C with 1 PLT in PR, followed by CR lasting 22mo+; 2 endometrial C including 1 with metastatic (M) D, having 1 PLT in PD followed by 1 SD and 1 PR lasting 69 mo+ and 30 mo+; 1 M prostatic C, having 1 PLT in PD followed by SD lasting 58 mo+; 3 head and neck C with 1 M having 1 PLT, all with PD followed by PR lasting 56 mo+, 12 mo+ and 6 mo+; 3 renal cell C including 2 M with 1 PLT in PD followed by 2 PR and 1 PD lasting 16 mo+ for 2 pts and 10 mo for 1pt; 2 liver C with 2 PLT, both in PD followed by PR lasting 18 mo+; 2 peritoneal C with 2 PLT in PD followed by 1 PD and 1 CR lasting 6 mo and 6 mo+; 3 M colon C, 1 with 1 PLT and 2 with 2 PLT, all in PD followed by 1 PR and 2 CR lasting 6 mo, 24 mo+ and 18 mo+; 2 gastric C with 1 and 2 PLT, all in PD followed by 1 PD and 1 PR lasting 6 mo and 6 mo+; 2 sarcomas including 1 Ewing, all with 2 PLT in PD followed by 1 PD and 1 PR lasting 9 mo and 9 mo+; 1 lung cancer with 2 PLT in PD followed by PD at 12 mo+; 1 M melanoma with 2 PLT in PD followed by PR at 6 mo+.

3 pts had HM including: 2 mantle cell lymphomas (MCL) with 3 PLT for 1 pt and 7 PLT for the other, all in PR after ibrutinib followed by CR under AV alone for 1 pt lasting 12 mo+. The second pt had leukemic C cells decreasing at 2 mo of AV alone; 1 transformed Waldenström's disease (WD) having 5 PLT, in PR after venotoclax followed by AV alone, with only IgM level at 4 g/L and no tumor, at 6 mo+.

9 pts were controlled with AV alone for 12 mo+. In 1 pt analyzed, 2 T-cell receptor (TCR) clonal rearrangements were observed in peripheral blood after 3 mo.

8 additional pts with HM had ongoing therapy and will be presented. 1 pt had GIST and follicular (F) L, 1 had WD, 1 had MCL, 3 had multiple myeloma with 1 responding at 4 injections, 1 pt with osteomyelofibrosis and 1 with myelodysplastic syndrome.

Conclusions. APAVAC is a simple method for AV with high clinical impact in very bad situations. It could be used in combination with other therapy and for residual disease control. Further clinical studies are planned in solid C as well as in HM.