-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4916 Optimized Double-Unit Cord Blood Transplantation Mitigates Transplant-Related Mortality Resulting in High Progression-Free Survival in Adults with Hematologic Malignancies

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, adult, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Myeloid Malignancies, Study Population, Human, Transplantation
Monday, December 11, 2023, 6:00 PM-8:00 PM

Ioannis Politikos, MD1,2, Sean M. Devlin, PhD3*, Stephanie Chinapen2*, Sean Quach, BSc4*, Parastoo B. Dahi, MD5,6*, Boglarka Gyurkocza, MD6,7, Ann A. Jakubowski, MD, PhD8, Esperanza B. Papadopoulos, MD6,7, Doris M. Ponce, MD, MS6,9, Roni Tamari, MD7, Andromachi Scaradavou, MD10 and Juliet N Barker, MBBS1

1Department of Medicine, Weill Cornell Medicine, New York
2Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
3Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
4Memorial Sloan Kettering Cancer Center, New York
5Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
6Department of Medicine, Weill Cornell Medical College, New York, NY
7Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
8Memorial Sloan-Kettering Cancer Ctr., New York, NY
9Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY
10Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY

Background: Double-unit cord blood transplantation (dCBT) with intermediate intensity conditioning (Cy50/ Flu150/ Thio10/ TBI400cGy) and cyclosporine-A (CSA)/ mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis has been associated with high progression-free survival (PFS) in adult patients (pts) with hematologic malignancies (Barker JN et al, Blood Advances 2020). Now, our Center has investigated multiple refinements to further mitigate transplant-related mortality (TRM). Herein, we have analyzed transplant outcomes in these adult dCBT pts to establish an optimized dCBT platform.

Methods: Consecutive adult first allograft pts with high-risk hematologic malignancies who underwent first allografts with intermediate intensity dCBT between 3/2018-8/2022 were analyzed. Optimizations involved further refined unit selection placing highest priority on unit quality (i.e. optimized banking practices) & CD34+ cell dose over HLA-match, ensuring therapeutic (CSA) levels (> 250 ng/mL) by day 0, prompt treatment of pre-engraftment syndrome (PES) & letermovir prophylaxis in CMV seropositive pts from day +7. Also, we have investigated 2 strategies to mitigate acute graft-versus-host disease (aGVHD): pts early in the study period received CSA, MMF & tocilizumab (8 mg/kg on day -1) prophylaxis (Toci Group), whereas recent pts (Recent Group) received CSA/ MMF with prompt therapy of clinically diagnosed aGVHD.

Results: Of 74 patients (Table), 49 were in the Toci Group, & 25 in the Recent Group. Most pts were transplanted for acute leukemia (n = 55, 74%) & over half (n = 39, 53%) had non-European ancestry. Distribution of diagnoses, CMV serostatus, HCT-CI & graft characteristics were similar between the groups but Recent Group pts tended to be younger (38 vs. 47 years, p = 0.071).

Toci Group pts had delayed neutrophil recovery [engraftment incidence 94% (95%CI: 87-99) at a median of 25 days (range 16-40), one graft failure], but low rates of PES (n = 19, 39%). The day-100 incidence of grade II-IV & III-IV aGVHD were 69% (95%CI: 56-82) & 10% (95%CI: 2-19), respectively. One pt (false negative CMV-serostatus) who did not receive letermovir had CMV infection. One-year TRM was 16% (95%CI: 6-27) with a 1-year relapse rate of 6% (95%CI: 3-13). TRM was due to infection (n = 3), aGVHD (n = 3, 1 with concurrent COVID-19 infection), multiorgan failure (n = 2) & graft failure (n = 1). With a median follow-up of 47 months (range 28-62), the 1-year OS was 84% (95%CI: 73-94) & 1-year PFS was 78% (95%CI: 66-89).

By contrast, the engraftment incidence in Recent Group pts was 100% with a faster median neutrophil recovery of 19 days (range 11-36, p = 0.002) & all engrafted platelets at a median of 36 days (range 24-92). However, most Recent group pts developed PES [n = 20 (80%), p < 0.001] although this responded promptly to short course corticosteroids. Day 100 grade II-IV aGVHD was also higher [92% (95%CI: 81-99), p = 0.009], although grade III-IV aGVHD was low [8% (95%CI: <1-19)] & similar to tocilizumab pts. Day 100 incidence of CMV was 0%. With a median follow-up of 17 months (range 6-50), the 1-year TRM in Recent Group pts is 0% with a 1-year relapse incidence of 13% (95%CI: 7-27). Consequently, the 1-year OS & PFS are high at 96% (95%: 89-99) & 87% (95%CI: 74-99), respectively (Figure).

Conclusions: Optimized dCBT with intermediate intensity conditioning, graft selection that prioritizes unit quality & CD34+ dose, CSA/ MMF prophylaxis with prompt therapy of PES & aGVHD, & letermovir CMV prophylaxis mitigates TRM in young & middle-aged adults. Thus, combined with relatively low relapse rates, the PFS & OS are high. Tocilizumab has been abandoned due to its notable association with delayed neutrophil engraftment & lack of survival advantage. Letermovir is highly effective completely preventing CMV infections & may contribute to the reduced aGVHD-related mortality recently (as compared to the pre-tocilizumab era), since avoidance of CMV antiviral therapy toxicities greatly facilitates aGVHD prevention & therapy. Given the rapid availability of cryopreserved unmanipulated CB grafts & frequent limitations of URD availability for minority populations, optimized dCBT is a highly attractive curative therapy for acute leukemias & other high-risk myeloid malignancies warranting prospective multi-center investigation.

Disclosures: Politikos: ExcellThera: Other: Membership on Data and Safety Monitoring Board ; Merck: Research Funding. Gyurkocza: Actinium Pharmaceuticals, Inc: Research Funding. Ponce: Evive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Ceramedix: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kadmon/Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Barker: Gamida Cell: Consultancy; New York Blood Center: Consultancy; Merck: Research Funding.

*signifies non-member of ASH