Giebel, Sebastian

Abstract Checkpoint inhibitors (CPIs) have shown remarkable efficacy in Hodgkin lymphoma (HL), and are now used routinely. While allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for HL, there are concerns prior CPIs may exacerbate post–allo-HCT complications, particularly graft-versus-host disease (GVHD), and lead to worse outcomes. Given the relative paucity of data, we performed a Center for International Blood and Marrow Transplant Research/European Society for Blood and Marrow Transplantation study to examine the impact of prior CPIs in allo-HCT. We included 2186 adult patients aged >18 years who received a first allo-HCT using a matched related, unrelated, or haploidentical donor from 2008 to 2023. Twenty-seven percent of patients received prior CPIs. GVHD prophylaxis was posttransplant cyclophosphamide (PTCy) in 55.8% of patients in the CPI cohort, and 35% in the non-CPI cohort. Median follow-up among survivors was longer for the non-CPI (39 months) than CPI cohort (16.5 months). In multivariate analysis, prior CPI exposure did not affect overall survival (OS) or nonrelapse mortality, but resulted in improved progression-free survival (non-CPI vs CPI hazard ratio [HR], 0.81; 0.67-0.98; P = .03) and lower relapse incidence (HR, 0.58; 0.45-0.76; P < 001). While grade 2 to 4 (HR, 1.26; 1.04-1.53; P = .02) and 3 to 4 (HR, 1.41; 1.04-1.92; P = .03) acute GVHD (aGVHD) were increased, differences in chronic GVHD (cGVHD) were not significant. PTCy–based GVHD prophylaxis resulted in improved OS, lower grade 2 to 4 aGVHD, and cGVHD in patients with prior CPI exposure. In summary, allo-HCT should still be considered a curative option for patients with HL in the era of CPIs.

In REACH3 (ClinicalTrials.gov identifier: NCT03112603 ), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.

Background: In 2015 the first B-cell acute lymphoblastic leukemia (B-ALL) patient receiving CAR T-cell therapy in Europe was reported to the EBMT registry. Today, the EBMT registry counts with more than 9000 patients treated with CAR T-cell therapies across all indications. Here, on behalf of the GoCART coalition, we present the outcomes of the largest European cohort of B-ALL patients treated with autologous, second generation, CD19-targeted CAR T-cells to date. Methods: Adult and paediatric patients with B-ALL received treatment with CAR T-cell therapy using either academic or commercially available products in 40 centres across 17 different countries. Safety was retrospectively assessed as per ASCTC 2019 consensus grading and CTCAE, and efficacy as per NCCN guidelines. Relapse incidence was defined as haematological relapse or progression after CART with non-relapse mortality as competing event. Leukemia free survival (LFS) was defined as being alive without occurrence of relapse. Follow-up includes patients treated from 2016 to Dec 2023 until data cutoff in June 2024. Results: A total of 345 patients (173 adults and 172 pediatrics) received therapy from 2016 to 2023 with tisagenlecleucel (65.2%), varnimcabtagene autoleucel (25.8%), brexucabtagene autoleucel (5.5%), and others (3.5%). Median age at infusion was 18 yrs. (range, 1.1-78.2) and 41.7% were females. High-risk features were identified including cytogenetic/genomic high-risk as per ELN guidelines (33.8%), relapse after allo-HCT (57.7%), early relapse (<1 year) after prior allo-HCT (30.4%), ≥3 prior treatment lines (55.5%) including prior exposure (and refractoriness) to blinatumomab and inotuzumab in 27.3% (34%) and 28.8% (32.3%), respectively. Median time from diagnosis to CART infusion was 2.8 years (0.1-17.9). Median time from last relapse prior CART to infusion was 2 months (range, 0.9-38.4). Bridging therapy was administered in 86.4% (298) of patients based on high or low intensity chemotherapy (32.1% or 26.5%, respectively), inotuzumab-ozogamicin (13.4%), TKI (8.2%), involved-site therapy (intrathecal chemotherapy, radiotherapy, orchiectomy) (3.5%), and blinatumomab (2.6%), alone or in combination. Prior to infusion, 34.7% had more than 5% BM blast count, 16.3% had circulating blasts in PB, and 20.6% had extramedullary disease. Lymphodepletion was performed in all but one patient, based on fludarabine and cyclophosphamide regimens. The reverse Kaplan-Meier median follow-up was of 2.2 years. The incidence of any grade (and severe) CRS was 71.6% (14.5%), and for ICANS was 15.7% (7.6%). The cumulative incidence of MRD-negative CR at month +3 was 76.9% (71.9-81.1), followed by a 2-year overall survival of 64.6% (58.7-69.8), leukemia-free survival of 48% (42.1-53.7), and relapse incidence of 45.5% (39.6-51.2). Non-relapse mortality at 2 years was 6.5% (4-9.6), 2-year cumulative incidence of subsequent HSCT of 33.3% (28-38.7) and second CAR-T infusions of 12.4% (8.8-16.6). Allogeneic HSCT after CAR-T was performed in 113 cases including 67 (59.3%) HSCT-naïve patients, due to molecular or overt disease relapse (60.9%), and other non-relapse reasons including suboptimal CAR-T persistence/B-cell aplasia (19.1%), pre-CAR-T high-risk features (13.6%), second malignancies (1.8%), and others. Second CAR-T infusions were performed in 39 cases due to molecular or overt disease relapse (79.5%) or suboptimal CAR-T persistence/B-cell aplasia in the absence of relapse (20.5%). Conclusions: The results from this European study demonstrate that CD19-targeted CAR T-cell therapy is an effective treatment for patients with high-risk B-cell ALL, providing substantial leukemia-free survival and overall survival rates despite the high-risk nature of the patient population. The necessity for bridging therapies and subsequent consolidative approaches, such as HSCT and second CAR T infusions, underscores the complexity and tailored nature of managing R/R B-ALL. These findings support the continued use and further investigation of CAR T-cell therapy in diverse clinical settings, emphasizing the importance of post-infusion strategies to sustain long-term remission. This will provide deeper insights into the factors influencing outcomes and help refine treatment protocols to improve patient care.

Background: The prognosis of patients (pts) with relapsed or refractory B ALL (r/r B-ALL) treated with CAR T-cells and receive a 2nd CART infusion is unknown. Few reports with limited numbers of patients suggest that 2nd CART infusion is feasible with questionable efficacy. This GoCART coalition registry study aimed at compiling data to investigate the indications, efficacy, and toxicity of CART2 infusion in pts with r/r B-ALL. Methods: This is a multicenter, retrospective registry study that included pediatric and adult patients with r/r B-ALL who received autologous CD19-targeted CAR T-cell therapy (CART1) and subsequently were treated with a second administration of CD19 and/or CD22-targeted CAR-T cell therapy (CART2) from 2017 to 2023. Baseline features, prior stem cell transplant (SCT), indications for CART2 and outcomes were collected. Relapse incidence (RI) was defined as overt recurrence, non-relapse mortality (NRM) as death without relapse occurrence, leukemia free survival (LFS) as being alive without occurrence of relapse and overall survival (OS) as being alive. RI and NRM were estimated using cumulative incidence function and OS and LFS Kaplan-Meier estimation. Results: Out of 345 pts who received CART1, 39 (2y cumulative incidence of second CART: 12.4% (95%CI: 8.8-16.6)) received CART2. Reasons for CART2 were overt relapse (n= 26; 66.7%), molecular relapse by measurable residual disease (MRD+) (n=5; 12.8%), and B-cell recovery (BCR) in the absence of relapse (n=8; 20.5%). Seventeen pts (43.6%) were female and median age at CART2 infusion was 19 yrs (range: 6.9-67.1), including 19 children and 20 adults. 74.4% of the pts had received a prior SCT, 25 pts (64%) before CART1, 2 (5.1%) only between CART1 and CART2, and 2 (5.1%) before CART1 and between CART1 and CART2. Among the 31 pts who received CART2 for relapse, this was CD19+ in 24 (92.3%), CD19- in 2 (7.7%), and unknown in 5. CART1 products were varnimcabtagene autoleucel (ARI-0001) (23), tisagenlecleucel (13), brexucabtagene autoleucel (1), and other experimental (2). All CART2 products targeted CD19 except 2 (1 CD22 and 1 dual CD19-CD22). Median time between CART1 and CART2 was 11.0 months. For patients who received CART2 for BCR, median time between CART1 and CART2 was shorter than for those who received it for relapse: 2.4 (IQR: 2.3-3.3) months vs. 12.4 (IQR:6.4-19.3) months. Regarding leukemic burden at the time of CART2 infusion, 19 pts (48.8%) were in overt relapse (14/19 with extramedullary disease, including 7 in CNS), 12 (30.1%) were in complete remission (CR) MRD+ and 8 (20.5%) CR MRD-. With a median follow-up time of 2.3 yrs [95% CI: 1.2-3.4], the 2-yr OS and LFS after CART2 were 47.1% [95% CI: 27.8-64.3] and 39.9% [95% CI: 24-55.3], respectively. 2-yr RI was 54.5% (95% CI: 36.5-69.4) and NRM was 5.6% (95% CI 1-16.8). 2-yr OS, LFS and RI for pts in CR at CART2 infusion irrespective to MRD were 76.1%, 63.3% and 25.6% while for those not in CR these outcomes were 17.7%, 15% and 85%, respectively (p= 0.007, 0.006 and 0.002). 2-yr LFS (71.4% [95% CI 25.8-92]) and RI (0%) was significantly better for pts receiving CART2 for BCR than in those who received it for relapse (31.6% [15.6-48.9] and 68.4% [46.7-82.8]; p= 0.036, p=0.002). Conclusion: This is a large registry study describing indications and outcome of CART2 in patients with r/r B-ALL. At 2-yrs after CART2, the LFS was of 39.9% and for patients receiving CART2 due to B-cell recovery was of 71.4%. These results show that CART2 is associated with low NRM and might be a bridge to SCT or other additional therapies. Updated results with data about subsequent therapies after CART2 will be presented at ASH meeting.

Introduction: Despite the success of anti-CD19 Chimeric Antigen Receptor T cells (CART19) in patients with B-cell acute lymphoblastic leukemia (B-ALL), an allogeneic haematopoietic stem cell transplantation (HSCT) might rescue patients with disease recurrence. However, in patients at high risk of relapse, indication and timing of HSCT are challenging. Whether waiting for detectable disease or proceeding to consolidative HSCT in remission, is still controversial. This GoCART Coalition registry study aimed at investigating the outcome of patients who received HSCT after CART19. Methods: We retrieved data from the EBMT registry on adults and children with B-ALL who received autologous CART19 from 2016 and 2023. Baseline, previous treatment, bridging therapy, CART19 therapy, B cell aplasia duration, outcome, disease status at follow-up were collected. Kaplan Meier estimates were used for overall survival (OS), leukemia-free survival (LFS) and non-relapse mortality (NRM) from date of HSCT, whereas cumulative incidence was used for relapse after HSCT. The relapse was defined as molecular or hematologic recurrence of the disease. Relapse and NRM were mutually competing events. Results: Of 345 patients (173 adults and 172 children) infused with CART19 (Tisagenlecleucel in 65.2%, Varnimcabtagene autoleucel 25.8%, brexucabtagene autoleucel 5.5%, and others 3.5%), 113 subsequently received an HSCT (37 adults and 76 children; median age 13.5 years, IQR 8.2-22.2) at a median of 6.2 months (3.7-11.8) after CART19 infusion. Median follow-up was 1.6 years (95%CI 1.1-1.9). Overall, 67/113 (59.3%) patients were transplant-naive (17 adults; 50 children). 78.2% received a myeloablative conditioning, 36.8% were grafted from a mismatched related donor. Most of the patients (64.2%) were transplanted in CR3 or more. Disease status at HSCT was relapsed disease for 9% of the patients, whereas among patients in CR with reported MRD 26/95 (27%) received HSCT with MRD positivity (MRD+). Among the patients with disease recurrence after CART19, 19/60 (32%) detected a CD19-negative clone. Indication for the subsequent HSCT was reported for 110 patients, as follow: (I) Rescue HSCT in 68 (62%) patients with molecular/morphological disease after CAR-T (including one patient with MDS post CAR-T); (II) Pre-emptive HSCT in 22 (20%) patients with B-cell aplasia loss with no signs of disease recurrence; (III) ConsolidativeHSCT in the 20 patients (18%) who were transplanted for the high risk of relapse, despite ongoing B cell aplasia and no disease recurrence. Median time elapsed between CART19 and HSCT was 9.5, 4.4 and 3.4 months in the three groups, respectively. The 2-yr OS was 71.1% (95%CI 59.8-79.7) and 2-yr LFS was 53.5% (41.9- 63.8), relapse incidence was 32.7% (22.4-43.5), while NRM was 11.6% (6.1-19.1). The 2-years LFS was 59.6% (45.2-71.4) vs 42% (19.2-63.4), for patients transplanted with negative or positive MRD, respectively. 5/11 patients transplanted with overt disease (including one with MDS) relapsed or died, the 6 survivors free of disease had follow-up inferior to 2 years. Children compared with adults showed better OS (76.8%, 62.1-86.4; 59.9%; 40.8-74.6; p=0.02), and better LFS (64.3%, vs. 36.4%; p= 0.02). Patients receiving a rescue HSCT for MRD+ or overt relapse had a significant lower LFS (43.6% and 33.2%), as compared to pre-emptive (77.3%) and consolidative HSCT (83.6%, p= 0.001). In univariate analysis, no significant differences in OS (74.5% vs 65.6%, p=0.32), LFS (54.3% vs 52.4%, p=0.75) and NRM (10.7% vs 12.9%, p=0.68) were reported for those patients having a previous HSCT before CART19. Conclusion: To the best of our knowledge this is the largest cohort of transplanted patients after CART19. In this “real-world” registry-based study we found that patients transplanted without disease recurrence had a better LFS, also accounting for MRD. For those who experienced molecular or overt relapse, achieving MRD negativity appeared to be relevant for a better outcome. The low NRM, with no differences between pre-transplanted and transplant naive patients, suggest that HSCT after CART19 is well tolerated, and represent a valid strategy to reduce the risk of relapse. As it remains unclear for which patients autologous CART19 cells remains a stand-alone treatment, future studies should focus on strategies for early identification of patients at higher risk of treatment failure.

Introduction: Corticosteroids (CS) are the standard first-line treatment for patients (pts) with chronic graft-versus-host disease (cGvHD), but pts can be unresponsive or become refractory to or dependent on CS (SR/D).Ruxolitinib (RUX), a JAK1/2 inhibitor, is approved for the treatment of pts ≥12 years of age with SR/D-cGVHD, based on the primary outcomes from the randomized, phase III REACH3 (NCT03112603) study, which demonstrated the superior efficacy of RUX vs best available treatment (BAT) in pts with SR/D-cGVHD. Here, we present the final, long-term efficacy and safety outcomes from REACH3. Methods: Pts ≥12 years of age with moderate or severe SR/D-cGVHD were randomized 1:1 to receive either RUX 10 mg twice daily (BID) or investigator-selected BAT and followed for 3 years, till discontinuation or death. The primary analysis was conducted at week 24 (Cycle 7 Day 1 [C7D1]) in randomized pts, then pts entered the extension period (C7-39) in which they continued treatment, switched from BAT to RUX (crossover cohort), or discontinued treatment and entered long-term survival follow-up (FU). Failure-free survival (FFS; key secondary endpoint), duration of response (DOR), overall survival (OS), non-relapse mortality (NRM), malignancy relapse (MR), and safety were analyzed at 3 years (week 156; final data cut off 15 Dec 2022). Overall response rate (ORR) and best overall response (BOR) during the crossover treatment period were analyzed for pts who switched from BAT to RUX on or after C7D1. Results: Of 329 pts randomized, 53 completed the treatment period and 276 discontinued, 115 entered survival FU (RUX: 73/165; BAT:42/164); 70 pts crossed over from BAT to RUX of which 16 completed the crossover treatment period and 24 entered survival FU. Median FFS was longer in the RUX vs BAT arms (38.4 vs 5.7 months; hazard ratio [HR]=0.361, 95% confidence interval [CI]: 0.268, 0.485) with 12-month FFS probabilities of 64.0% (95% CI: 56.1, 70.8) and 28.8% (95% CI: 21.8, 36.1), respectively. Median OS was not reached and there was no difference in risk of death between the arms (HR=0.851, 95% CI: 0.544, 1.331) [Table 1]. Median DOR was 6.4 months (95% CI: 4.9, 11.4) in the BAT arm but was not reached for the RUX arm; notably, the probability of maintaining DOR at 3 years was higher in RUX (59.6%; 95% CI: 50.4, 67.6) vs BAT (26.7%; 95% CI: 18.5, 35.5). NRM event rates were similar between the arms (RUX: 29/165; BAT 34/164), and MR events were similar and low in both arms (13/156 and 11/160, RUX and BAT respectively) up to 3 years. The ORR at week 24 after crossover from BAT to RUX was 50.0% (95% CI: 37.8, 62.2), including complete response (CR) in 4 (5.7%) pts and partial response (PR) in 31 (44.3%) pts. The BOR during crossover was 81.4% (95% CI: 70.3, 89.7), including CR of 7.1% and PR of 74.3%; disease progression only occurred in 1 pt. Almost all pts treated during the main treatment period (RUX: 100%; BAT: 93.7%) experienced ≥1 adverse event (AE) and, in general, AE rates were higher in the RUX vs BAT arms [Table 2], likely due to prolonged FU and exposure to RUX (median exposure to treatment of 52.9 weeks vs. 24.1 weeks for RUX and BAT, respectively).Anemia was the most common AE (RUX: 33.9%; BAT: 15.8%) and grade ≥3 AE for RUX (17.6% vs BAT 9.5%, respectively); grade ≥3 neutropenia, thrombocytopenia, alanine aminotransferase increase, and gamma-glutamyltransferase increase were also ≥5% higher for RUX than BAT. Anemia (24.2%; grade ≥3, 10.3%) and thrombocytopenia (3.8%) were the most common RUX and BAT treatment-related AEs, respectively. Infections, excluding tuberculosis, were the most common AE of special interest (77.6% vs. 68.4%; grade ≥3, 31.5% and 26.6%, for RUX and BAT, respectively). On-treatment deaths were mainly due to cGvHD (n/N, RUX: 10/18; BAT 6/12). Conclusions: After 3 years of treatment in REACH3, the longer FFS and higher DOR with RUX vs BAT indicated that cGVHD was more in control with RUX treatment. Notably, efficacy was demonstrated in pts who switched from BAT to RUX with an ORR similar to that in pts randomized to RUX. RUX was well tolerated with no unexpected toxicities and safety that was consistent with earlier studies. Overall, the long-term control of cGVHD and tolerability of RUX was demonstrated for pts ≥12 years of age with SR/D-cGvHD.

Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.

Abstract Background: A recent study from the Acute Leukemia Working Party of EBMT demonstrated that outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adults with acute lymphoblastic leukemia (ALL) have improved significantly over time and that total body irradiation (TBI) should be considered as the preferable type of myeloablative conditioning (MAC). This study, however, did not compare outcomes of allo-HCT in patients with CNS involvement (CNS-pos) vs. those without CNS disease (CNS-neg). Study population: Here, we evaluate post allo-HCT outcomes of 547 patients (CNS-pos at initial presentation=96, CNS-neg=451) who underwent the procedure in first complete remission (CR1) between 2009 and 2019 at an EBMT participating transplant center. The distribution of ALL subtypes were as follows: CNS-pos (Ph-neg B ALL=28%, Ph-pos B ALL=27%, and T-cell ALL=45%) and for CNS-neg (Ph-neg B ALL=21%, Ph-pos B ALL=44%, and T-cell ALL=35%), p=0.01. The primary endpoint was leukemia-free survival (LFS). Results: The median follow up was not statistically different between the CNS-pos (78.7 months) and the CNS-neg group (67.2 months), p=0.58. Patients in the CNS-pos group were younger (median age 31.3 vs. 39.7 years, p=0.004), received the procedure more recently (median year 2012 vs. 2010, p=0.003), were less likely to have a Karnofsky score of equal or higher than 90 (70.8% vs. 81.9%, p=0.017), or to have received peripheral blood stem cells (PBSC) (61.5% vs. 72.7%, p=0.028). The groups did not differ in regards to donor source (URD, 50% vs. 56.5%, p=0.24) or the intensity of the preparative regimen (MAC, 82.3% vs. 85.6%, p=0.41). In multivariate analysis, CNS-pos were associated with higher cumulative incidence of relapse (HR=1.58 (95%CI=1.06-2.35), P=0.025) and a trend for an inferior leukemia-free survival (LFS) (HR=1.38 (95%CI=0.99-1.92), p=0.057), but did not adversely impact overall survival (OS) (HR=1.28 (95%CI=0.89-1.85), p=0.18). A subgroup multivariate analysis limited to patients with CNS-pos showed that prescribing a TBI MAC regimen (vs. others) results in a lower cumulative incidence of relapse (HR=0.35 (95%CI=0.15-0.79), p=0.012) and better LFS (HR=0.43 (95%CI=0.22-0.83), p=0.01) and OS (HR=0.44 (95%CI=0.21-0.92), p=0.03). Use of PBSC (vs. BM) was also independently associated with better OS (HR=0.53 (95%CI=0.29-0.99), p=0.046). Conclusion: Notwithstanding the inherent limitations of registry data, particularly ascertaining the absence of CNS involvement in the CNS-neg group, our results show CNS involvement as an independent risk factor for relapse following allo-HCT. Our data support, nonetheless, the choice of a TBI-based MAC regimen in this group of patients but stresses the need for close monitoring of relapse after allo-HCT. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Mielke: Immunicum: Other: Data safety monitoring board; DNA Prime SA: Speakers Bureau; Gilead/KITE: Other: Travel support, Expert panel ; Miltenyi: Other: Data safety monitoring board; Novartis: Speakers Bureau; Celgene/BMS: Speakers Bureau. Socie: Alexion: Research Funding. Huynh: Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.