PS1241 CHECKPOINT INHIBITOR TREATMENT BEFORE HAPLOIDENTICAL TRANSPLATATION IN RELAPSED OR REFRACTORY HODGKIN LYMPHOMA (HL) PATIENTS IS ASSOCIATED WITH HIGHER PFS WITHOUT INCREASED TOXICITIES
Authors: C. De Philippis, F. Legrande, S. Bramanti, C. Montes de Oca, R. Dulery, R. Bouabdallah, A. Granada, R. Devillier, J. Mariotti, B. Sarina, S. Harbi, V. Maisano, S. Furst, T. Pagliardini, P. Weiller, C. Lemarie, B. Calmels, C. Chabannon, C. Carlo‐Stella, A. Santoro, M. Mohty, D. Blaise, L. Castagna
Journal: HemaSphere (2019)

Background: Immune checkpoint inhibitors (CPI) before allogeneic stem cell transplantation (SCT) could enhance allogeneic T‐cell responses, increasing both the graft‐versus‐tumor effect and the incidence of immune complications. Aims: The aim of this study was to compare the outcomes of patients who received CPI before haploidentical (haplo)‐SCT to patients who underwent haplo‐SCT without prior CPI. Methods: We retrospectively analyzed the outcome of 52 consecutive HL patients undergoing haplo‐SCT with post‐transplant cyclophosphamide as Graft Versus Host Disease (GVHD) prophylaxis at 3 centers between 2014 and 2018. Patients’ characteristics are listed in Table 1. The two cohorts (CPI treatment before SCT = 28 patients and no CPI treatment before SCT = 24 patients) were similar in their main pre‐transplant characteristics, except for the CPI group who received more lines of therapy before SCT (4 vs 6, p = 0.0006). Results: After a median follow‐up of 26 months (range 7.5–55), taking into account all the patients, the 6‐months cumulative incidence (CI) of acute GVHD grade 2–4 was 33% (95% CI, 20–45), whereas the 2‐year CI of moderate to severe chronic GVHD was 11.5% (95% CI, 4–24). The 1‐year CI of NRM was 15% (95% CI, 8–31) and the 2‐year CI of relapse was 13% (95% CI, 5–25). The 2‐year OS and PFS were 78% (95% CI, 62–88) and 69.5% (95% CI, 52–82), respectively. In univariate analysis, prior use of CPI had no effect on either acute or chronic GVHD. The 6‐ months CI of grade 2–4 aGVHD was 39% (95% CI, 21–57) in the CPI group and 25% (95% CI, 10–44) in the non‐CPI group (p = 0.23), while the 2‐year CI of moderate to severe cGVHD was 16% (95% CI, 3–39) and 9% (95% CI, 1–26), respectively (p = 0.67). The 2‐year CI of relapse in the CPI group was only 4% (95% CI, 0–16) versus 22% (95% CI, 8–41) (p = 0.08) in the non‐CPI group. A significantly higher 2‐year PFS was observed in the CPI group (89% (95% CI, 70–96) vs 54% (95% CI, 31–72), p = 0.029)). No differences were observed in OS and NRM between the two cohorts: the 2‐year OS was 88% (95% CI, 66–96) in the CPI group vs 71% in the non‐CPI group (95% CI, 47–86) (p = 0.30) and the 2‐year CI of NRM was 11% (95% CI, 4–27) vs 24% (95% CI, 8–44) (p = 0.26), respectively. Based on the other pre‐transplant characteristics, only a correlation between disease status at SCT and OS was found: the 2‐year OS was 84% (95% CI, 61–94) in CR patients, 73% (95% CI, 35–91) in PR patients and 50% (95% CI, 6–85) in PD/SD patients (p = 0.04). In multivariate analysis, disease status other than CR had a negative impact on OS (hazard ratio (HR) 6.18 (95% Cl, 1.13–33, 72) for PR and HR 14 (95% CI, 199–98.29) for PD/SD). Treatment with checkpoint inhibitors before SCT was an independent protective factor for PFS (HR 0. 23 (95% CI, 0.05–0.92)). Summary/Conclusion: Treatment with CPI as a bridge to haplo‐SCT significantly improves the PFS in relapse/refractory HL, lowering the relapse rate, and does not enhance the toxicity. However, the main limitation of our study lies in the small number of patients; further studies are warranted to extend our findings. image