1San Raffaele Scientific Institute, Hematology and Bone Marrow Transplantation Unit, Milan, Italy, 2Université Pierre and Marie Curie, Paris, France, 3Unite´ de Recherche Mixte en Sante´ (UMR_S) 938, INSERM, Paris, France, 4Hôpital Saint-Antoine, AP-HP, Service d'Hématologie Clinique et Thérapie Cellulaire, Paris, France, 5Essen University Hospital, Institute for Experimental Cellular Therapy, Essen, Germany, 6Raisa Gorbacheva Memorial Research Institute, The First Pavlov State Medical University of St-Petersburg, Hematology and Transplantation, St Petersburg, Russian Federation, 7University Hospital Eppendorf, Department of Stem Cell Transplantation, Hamburg, Germany, 8Erasmus MC Cancer Institute University Medical Center Rotterdam, Rotterdam, Netherlands, 9Hospital Clinic, Institute of Hematology & Oncology, Dept. of Hematology, Barcelona, Barcelona, Spain, 10University Medical Center, Department of Hematology, Amsterdam, Netherlands, 11Institute of Hematology and Blood Transfusion, Servicio de Hematología, Prague, Prague, Czech Republic, 12Asklepios Clinic St. Georg, Hamburg, Germany, 13Institut Paoli Calmettes, Transplant and Cellular Therapy Unit, Marseille, France, 14Chaim Sheba Medical Center, Tel-Hashomer, Israel
Background: PTCy is largely adopted as GvHD-prophylaxis backbone in haploidentical transplantation. The encouraging results prompted investigations to assess PTCy also in unrelated donor (UD) setting. High-resolution HLA-matching contributes to UD-HSCT success; however, due to the selective in-vivo deletion of alloreactive T-cells, PTCy could modulate HLA-matching impact on UD-HSCT.
Methods: We compared the outcomes of acute leukemia patients receiving 10/10 (n=431) and 9/10 (n=234) HLA-allele matched UD-HSCT with PTCy GvHD-prophylaxis, reported to the ALWP-EBMT in 2010-2017. Primary endpoint was GvHD-free & Relapse-free survival (GRFS). Secondary endpoints were leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD, relapse and transplant-related mortality (TRM). Table 1 illustrates patients' characteristics. The power to detect a 2-years 10% difference GRFS between the 2 groups was 83% (alpha 2-sided=5%).
Results: Outcome endpoints at 2 years were not different between 10/10 and 9/10 UD-HSCT (GRFS: 42±5% and 43±7%, p=0.5; LFS: 56±5% and 55±7%, p=0.7; OS: 63±5% and 60±8%, p=0.9, respectively). The 100-day CI of grade≥2 and grade≥3 aGvHD were comparable for 10/10 and 9/10 UD (31±5% and 28±6%, p=0.4 and 10±3% and 9±3%, p=0.5, respectively). Likewise, the 2-y CI of cGvHD and extensive cGvHD were similar between 10/10 and 9/10 UD (32±5% and 38±7%, p=0.2 and 17±4% and 15±5%, p=0.4, respectively). The 2-y CI of TRM was 19±4% after 10/10 and 17±5% after 9/10 UD-HSCT (p=0.4). Relapse incidence at 2-y was 25±5% for 10/10 and 28±6% for 9/10 UD-HSCT (p=0.6).
After adjustment for diagnosis, patient age, disease status, Karnofsky PS, donor/patient gender and CMV, conditioning intensity, additional use of ATG, the multivariable model showed no effect of donor HLA-matching on outcomes. Compared to 10/10 UD, the hazards for GRFS was 0.9 for 9/10 UD (p=0.2), the HR for LFS was 0.9, p=0.3 and the HR for OS was 1, p=0.8. Moreover, compared to 10/10 UD, 9/10 UD-HSCT yelded similar hazards for grade≥2 aGvHD (HR: 0.8, p=0.2), cGvHD (HR: 1.2, p=0.3), TRM (HR: 0.7, p=0.2) and relapse (HR: 1, p=0.9). No interaction was found between donor type and additional ATG use. Variables associated with GRFS were active disease (HR 2.1 compared to 1st CR, p< 10-5) and Karnofsky PS≥90% (HR 0.6, p< 10-5).
Conclusions: In the present series of acute leukemia patients transplanted with PTCy, we report comparable survival with 9/10 and 10/10 HLA-matched UD-HSCT, across all disease stages, suggesting that this platform could alleviate the detrimental effect of single HLA-allele mismatching. These results warrant prospective comparative trials of PTCy versus standard use of ATG-based GVHD prophylaxis in matched and mismatched UD-HSCT.
|10/10-UD (n=431)||9/10-UD (n=234)||p|
|Median follow-up, months||18 (5-35)||20 (11-31)||0.5|
|Patient median age||43 (18-76)||48 (19-73)||0.1|
|Diagnosis: AML; ALL||313 (73%); 118 (27%)||170 (73%); 64 (27%)||0.9|
|Disease status: CR1; CR>1; Advanced||278 (64%); 82 (19%); 71 (17%)||134 (57%); 57 (24%); 43 (19%)||0.2|
|Karnofsky PS ≥90%||314 (75%)||162 (72%)||0.3|
|Cell source: PB; BM||386 (90%); 45 (10%)||205 (88%); 29 (12%)||0.4|
|Conditioning: RIC; MAC||193 (45%); 238 (55%)||99 (42%); 135 (58%)||0.5|
|Additional ATG use||126 (29%)||75 (32%)||0.4|
Disclosure: Nothing to declare