Underscoring its commitment to expanding access to cell and gene therapy, NMDP/Be The Match®, the leading global partner working to save lives through cellular therapy, presented research today at the American Society of Hematology (ASH) Annual Meeting & Exhibition, which demonstrated that the use of post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GvHD) prevention significantly reduces the risk of transplant across the human leukocyte antigen (HLA) barrier and has the potential to level the playing field for patients with mismatched donors.

The study shows the practice-changing potential of using mismatched unrelated donors (MMUD) to expand access to all patients regardless of ancestry.

For populations currently facing the lowest odds of finding a fully matched donor, this could result in a nearly three-fold increase in the likelihood of securing a suitable donor and offering cell transplantation as a viable, life-saving therapy. [1]

“Historically, transplant outcomes following MMUD hematopoietic cell transplantation (HCT) using calcineurin inhibitor (CNI)-based GvHD prophylaxis have been poor,” noted Jeffery Auletta, Senior Vice President, NMDP/Be The Match and Chief Scientific Director, CIBMTR® (Center for International Blood and Marrow Transplant Research®), a nonprofit research collaboration between the National Marrow Donor Program (NMDP)/Be The Match, in Minneapolis, and the Medical College of Wisconsin, in Milwaukee.


Research shows no discernable differences in graft versus host disease, relapse free survival or overall survival for patients who had a Hematopoietic Cell Transplant (HCT) with an 8/8 or 7/8 Unrelated Donor (URD) for adult patients with malignancies. 

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“However, PTCy has transformed the allogeneic HCT landscape, enabling successful use of mismatched related and unrelated donor HCT by transcending the HLA barrier,” Auletta said.

“This research not only confirms the efficacy of PTCy, but also alludes to its promise to provide allogeneic HCT to essentially all patients irrespective of their ancestry. That promise is a message of hope to our patients.” he added.

Listen to Episode 106: Be The Match®: Improving Outcomes and Providing Hope to Patients in Need.

The results of study, “Post-Transplant Cyclophosphamide Eliminates Disparity in GvHD-Free, Relapse-Free Survival and Overall Survival between 8/8 Matched and 7/8 Mismatched Unrelated Donor Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies,” shows that this approach could significantly expand access to allogeneic HCT for patients of various ancestries, as finding a fully matched donor is no longer crucial for successful outcomes. It also suggests that although 8/8 URD HCT remains the best option if available, a 7/8 URD and haploidentical-related BMT donor are viable alternatives that warrant further comparative study. In summary, study results indicated that with PTCy GvHD prophylaxis:

  • No discernable differences in GvHD-free, relapse-free survival (GRFS) or overall survival (OS) were noted for patients receiving either 8/8 or 7/8 URD HCT.
  • 8/8 URD HCT showed a lower rate of moderate/severe chronic GvHD compared to 7/8 URD HCT.
  • 8/8 URD HCT had better GRFS and OS than haploidentical-related HCT, mainly due to higher rates of non-relapse mortality (NRM) and chronic GvHD in patients who received a haploidentical-related HCT.
  • Larger numbers for the 7/8 URD HCT group will be needed in order to compare outcomes between 7/8 URD and haploidentical-related HCT.

The study was designed to determine if PTCy can eliminate disparities in GRFS and OS between matched (8/8) and single mismatched (7/8) URD compared to haploidentical (half matched)-related donors. Patient data included first unrelated or haploidentical-related donor HCTs conducted in the US between 2017 and 2020. The study population included adult (age ≥18y) patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or myelodysplastic syndromes (MDS) undergoing their first 8/8 (n=1517 patients) or 7/8 (n=540 patients) URD or haploidentical (n=2772 patients) HCT and receiving PTCy.

The results of the study were presented at the 2023 Annual Meeting & Exhibition of the American Society of Hematology, , Session: 722, Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Advancements in GVHD Management, today at 11:45 am.

Clinical study
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide (ACCESS) – NCT04904588

Reference
[1] Auletta JJ, Al Malki MM, DeFor T, Shaffer, BC, Gooptu M, Bolanos-Meade J, Abboud R, Briggs AD, Khimani F, Modi D, Newcomb R, Shpall EJ, Bupp C, Spellman SR, Stefanski HE, Jimenez Jimenez AM, Devine SM. Post-Transplant Cyclophosphamide Eliminates Disparity in GvHD-Free, Relapse-Free Survival and Overall Survival between 8/8 Matched and 7/8 Mismatched Unrelated Donor Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies. Presented on Monday, December 11, 2023 during the annual meeting of the American Society of Hematology Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Advancements in GVHD Management
Hematology Disease Topics & Pathways. Blood (2023) 142 (Supplement 1): 780. [Abstract][Article]

Featured image: ASH 2022- Photo Courtesy: 2022 – 2023 © ASH/Matt Herp. used with permission.

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