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

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