Abedin Sameem M, Martens Michael J, Bolaños-Meade Javier, Al Malki Monzr M, Lian Qinghua, Runaas Lyndsey, Elmariah Hany, Gooptu Mahasweta, Larkin Karilyn, Shaffer Brian C, Loren Alison W, Solh Melhem M, Alousi Amin Majid, Jamy Omer, Perales Miguel-Angel, Rezvani Andrew R, Bhatt Ami S, El Jurdi Najla, Yao Janny M, Applegate Kristy, Kean Leslie S, Efebera Yvonne A, Reshef Ran, Clark William Bennett, Leifer Eric, Saber Wael, Horowitz Mary M, Jones Richard J, Holtan Shernan G, Hamadani Mehdi
Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Center for International Blood and Marrow Transplantation Research, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Blood Adv. 2025 Apr 30. doi: 10.1182/bloodadvances.2025015964.
Allogeneic hematopoietic cell transplant (allo-HCT) is underutilized in adults aged ≥ 70 years. Morbidity, often driven by graft-vs-host disease (GVHD), is considered a major barrier to its use. BMT CTN 1703 randomly assigned adults with hematologic malignancies undergoing allo-HCT after reduced intensity conditioning to receive either post-transplant cyclophosphamide, mycophenolate mofetil, and tacrolimus (PTCy) or tacrolimus and methotrexate (Tac/MTX) for GVHD prophylaxis. Overall study results revealed superior GVHD-free, relapse-free survival (GRFS) with PTCy-based prophylaxis. This analysis explored the impact of PTCy in patients ≥ 70 years enrolled to BMT CTN 1703. We analyzed outcomes for 96 patients aged ≥ 70 years. PTCy maintained superiority for the primary endpoint with a GRFS rate of 67.1% compared to 29.5% with Tac/MTX (p=0.001). GVHD control and improved immunosuppression-free survival contributed to a lower 1-year non-relapse mortality (NRM) with PTCy. Further, lower rates of relapse/progression were observed with PTCy, altogether resulting in significantly improved adjusted 1-year survival with PTCy at 94.3% versus 60.2% with Tac/MTX (p=0.001). PTCy based GVHD prophylaxis should be considered standard prophylaxis for older adults. Given low rates of NRM and excellent survival outcomes with this approach, there should be greater consideration for allo-HCT in older patients, particularly patients ≥ 70 years.
异基因造血细胞移植（allo-HCT）在70岁及以上的成年人中未得到充分利用。通常由移植物抗宿主病（GVHD）驱动的发病率被认为是其应用的主要障碍。BMT CTN 1703将接受减低强度预处理后进行allo-HCT的血液系统恶性肿瘤成年患者随机分为两组，一组接受移植后环磷酰胺、霉酚酸酯和他克莫司（PTCy）用于预防GVHD，另一组接受他克莫司和甲氨蝶呤（Tac/MTX）。总体研究结果显示，基于PTCy的预防方案具有更好的无GVHD、无复发生存率（GRFS）。该分析探讨了PTCy对纳入BMT CTN 1703研究的70岁及以上患者的影响。我们分析了96例70岁及以上患者的结局。PTCy在主要终点方面保持优势，GRFS率为67.1%，而Tac/MTX为29.5%（p = 0.001）。GVHD的控制和免疫抑制-free生存期的改善导致PTCy组1年非复发死亡率（NRM）较低。此外，PTCy组的复发/进展率较低，总体导致PTCy组调整后的1年生存率显著提高，为94.3%，而Tac/MTX组为60.2%（p = 0.001）。基于PTCy的GVHD预防应被视为老年人的标准预防方案。鉴于这种方法的NRM率较低且生存结局良好，应更多地考虑对老年患者，特别是70岁及以上的患者进行allo-HCT。
