Work

Adoptive transfer of ex vivo costimulated autologous T-cells after autotransplantation for myeloma (MM)accelerates post-transplant T-cell recovery

Year: 2004

Type: article

Abstract: Ex-vivo co-stimulation of autologous T-cells using anti-CD3/anti-CD28-conjugated magnetic beads may restore T-cell responsiveness toward MM cells. 40 patients (pts) received ex-vivo co-stimulated autologous T-cells after autotransplantation. The mean age was 58 (range 43–72), 72% were male, 24% had IgA paraproteins, 12% had del 13 or complex karyotypes and the median β2m level at diagnosis was 3.32 mg/L (range 1.09–73.7). Lymphocyte collections were followed by cyclophosphamide (4.5 g/m2) G-CSF for stem cell mobilization melphalan (200 mg/m2 or 140 mg/m2 for pts ≥70). T-cells were cultured for 12 days with anti-CD3/anti-CD28-immobilized immunomagnetic beads & IL-2 supplementation (100 units/ml). During a run-in phase, 12 pts received T-cells post-transplant (∼day +12) alone; afterwards, 28 pts participated in a 2 × 2 randomization in which they received T-cells “early” (day +12) or “late” (day +100) after transplant also received 2 immunizations with the pneumococcal conjugate vaccine (PCV, Prevnar®) days +30 +90 or 3 immunizations (prior to T-cell collection, days +30, +90) to test immune responses. 27 pts received 1 or more PCV immunizations and there were no grade 3/4 adverse events. Anti-pneumococcal antibody T-cell response assays are underway for pts who completed the study. 33 pts received a mean of 8.11 × 109 costimulated T-cells (range 1.6–11) all infusions were well tolerated. There were no delayed adverse effects except for grade 1–2 facial/upper body rashes in 6 pts (median 13 days after T-cells) and 1 episode of grade 2 conjunctivitis. At T-cell harvesting, the mean % of CD3 + cells in culture was 94.2% the mean T-cell doubling level was 5.2. Among the randomized pts, at day + 42 post-transplant (∼30 days after T-cell infusion for the “early” groups), the mean CD4/CD3 count was 679/μl (95% CI, 347–1012) for the “early” T-cell recipients vs 278/μl (95% CI, 59–497) for the “late” T-cell recipients (T-cells not yet infused) [P = 0.03]. The mean CD8/CD3 counts were 1826/μl (95% CI, 1275–2376) 1105/μl (95% CI, 404–1806) for the “early” and “late” T-cell recipient respectively at day +42 [P = 0.07]. 32 pts were evaluable for clinical responses (8 are too early). There were 6 CRs, 15 VGPRs (≥90% reduction in paraprotein levels), 10 PRs (50–90% reductions), 1 pt had no response. Post-transplant infusions of ex-vivo expanded autologous T-cells are feasible and well-tolerated may be associated with accelerated T-cell recovery.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2003.12.089