Back to Authors

Wang, Hailin

https://orcid.org/0000-0002-1843-999X

Mayo Clinic

18Kite, a Gilead company, Santa Monica, CA

Citations 15

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity
Jacobson, Caron A. , Ghobadi, Armin , Ahmed, Sairah , Miklos, David B. , Perales, Miguel‐Angel , Fingrut, Warren , Pennisi, Martina , Gowda, Lohith , Abid, Muhammad Bilal , Hong, Sanghee , Kharfan‐Dabaja, Mohamed A. , Khurana, Arushi , Badar, Talha , Hu, Zhen‐Huan , Wang, Hailin , Baer, Anjani, Baro, Elande , Miao, Harry , Spooner, Clare, Xu, Hairong, Pasquini, Marcelo C. , Ghobadi, Armin , Ahmed, Sairah , Miklos, David B , Perales, Miguel-Angel , Fingrut, Warren B , Shadman, Mazyar , Majhail, Navneet S , Kharfan-Dabaja, Mohamed A , Badar, Talha , Bennani, N Nora , Herr, Megan M. , Pasquini, Marcelo , Abid, Muhammad Bilal , Locke, Frederick L. , Siddiqi, Tanya , Muñoz, Javier , Gauthier, Jordan , Shadman, Mazyar , Mirza, Abu‐Sayeef , Majhail, Navneet S. , Lin, Yi , Bennani, N. Nora

Blood | April 18, 2024 | Volume: 143 | Issue: 26 | Pages: 2722-2734

10.1182/blood.2023023447 Get It

Abstract Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell–associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.
Benefit of axicabtagene ciloleucel versus chemoimmunotherapy in older patients and/or patients with poor ECOG performance status with relapsed or refractory large B‐cell lymphoma after 2 or more lines of prior therapy
Lunning, Matthew A. , Wang, Hailin , Hu, Zhen‐Huan , Jacobson, Caron A. , Miklos, David B. , Hill, Brian T. , Neelapu, Sattva S. , Dieyi, C., Field, Polly, Miao, Harry , Shahani, Shilpa, Patel, Anik R. , Spooner, Clare, Fu, Christine, Muramoto, David, Xu, Hairong, Pasquini, Marcelo C. , Westin, Jason R , Miklos, David B , Locke, Frederick L. , Siddiqi, Tanya , Ahmed, Sairah , Lin, Yi , Ghobadi, Armin , Westin, Jason R.

American Journal of Hematology | March 20, 2024 | Volume: 99 | Issue: 5 | Pages: 880-889

10.1002/ajh.27283 Get It

AbstractAxicabtagene ciloleucel (axi‐cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real‐world effectiveness of axi‐cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi‐cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR‐1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow‐up of 24 months for patients receiving axi‐cel and 60 months for patients receiving CIT, 12‐month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24–0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi‐cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi‐cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi‐cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi‐cel in older patients and patients with ECOG PS = 2 with R/R LBCL.
Comparative Effectiveness of Axicabtagene Ciloleucel Vs Historical Standard-of-Care in Patients with Relapsed or Refractory Follicular Lymphoma: An Analysis of CIBMTR and SCHOLAR-5 Data
Kambhampati, Swetha , Wang, Hailin , Yan, Jiali , Herrera, Alex F. , Frank, Matthew J. , Popplewell, Leslie , Best, Timothy, Fu, Christine, Beygi, Sara , Ray, Markqayne D, Bian, John, Hu, Zhen‐Huan , Pasquini, Marcelo C. , Jacobson, Caron A. , Ahmed, Nausheen , Lin, Yi , Locke, Frederick L. , Ghione, Paola , Gribben, John G. , Ray, Markqayne D. , Sun, Fang

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 2121-2121

10.1182/blood-2023-178629 Get It

Background: Axicabtagene ciloleucel (axi-cel), an autologous chimeric antigen receptor (CAR) T-cell therapy, achieved an overall response rate (ORR) of 94% and a complete response (CR) rate of 79% in patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more prior lines of therapy in the ZUMA-5 trial ( Jacobson et al. Lancet Oncol. 2022). Since its FDA approval in March 2021, there has been little evidence on comparative effectiveness (CE) studies of axi-cel vs standard-of-care (SoC), except ones using ZUMA-5 and historical SCHOLAR-5 data (eg, Ghione et al. Blood. 2022). This study was aimed to address this evidence gap in CE of axi-cel vs SoC used to treat r/r FL in real-world settings. Methods: The two data sources in this study were patients who received commercial axi-cel between March 2021 and May 2023 from the CIBMTR and patients who received historical SoC (eg, chemotherapy, anti-CD20 mAb + chemotherapy, immunomodulatory imide drugs) between July 2014 and December 2020 from SCHOLAR-5, which served as an external control of ZUMA-5 trial. The index date was defined as the initiation date of either the infusion for axi-cel patients or the last eligible systemic therapy for SoC patients. Patients were included if they were age ≥ 18, had documented r/r FL with histological grade 1, 2 or 3a, and received at least 2 prior lines of therapy at the index. Patients were excluded if they had transformed diffused large B-cell lymphoma, central nervous system involvement, prior receipt of CAR T or other non-CAR T cellular therapies or allogeneic stem cell transplant, or no post-index information on outcomes. Four effectiveness outcomes were ORR, CR rate, progression-free survival (PFS), and overall survival (OS). Imbalance in observed prognostic risk factors between the two was adjusted via a propensity score analysis using the standard mortality ratio weighting (SMRW). The primary analyses included weighted univariable analysis and multivariable logistic (ORR and CR rate) or Cox (PFS and OS) regressions that were adjusted for the covariates after the SMRW. A sub-analysis of patients age ≥ 65 was conducted using the same methods as the primary analyses. Results: The unweighted study cohort included 376 patients, in which 256 (68%) received axi-cel . Thepatients who received axi-cel were more likely to be younger (median age 61 for axi-cel vs 67 for SoC), have grade 3a FL (37% vs 12%), received 3 or more prior lines of therapy (83% vs 58%), or remained refractory to the last prior therapy (79% vs 73%) vs those who received SoC. The imbalance in the observed prognostic risk factors was mitigated via the SMRW. The weighted univariable analysis, in which the sample size by treatment reflected the SMRW, is shown in Table 1. In patients of all ages, ORR was 92% in axi-cel vs 67% in SoC, and CR rate was 84% vs 37%. Because of varying follow-up lengths by treatment (median 7 months for axi-cel and 37 months for SoC), survival outcomes were reported at month 6, at which time PFS rate was 88% in axi-cel vs 64% in SoC and OS rate was 97% vs 85%. The corresponding proportions for patients age ≥ 65 were similar to those reported for patients of all ages. In the weighted multivariable regressions, axi-cel was associated with statistically significantly better outcomes by all 4 effectiveness measures vs SoC (Table 1). Specifically, in patients of all ages, the odds ratios for axi-cel were 4.93 (95% CI, 2.35−10.34) for ORR and 16.72 (95% CI, 7.03−39.73) for CR rate, and the hazard ratios for axi-cel were 0.41 (95% CI, 0.22−0.77) for PFS and 0.15 (95% CI, 0.06−0.34) for OS. Similar to the patients of all ages in the primary analyses, patients age ≥ 65 in the sub-analysis also demonstrated improved outcomes associated with axi-cel (Figure 1). Conclusions: This study showed that patients with r/r FL after two or more prior lines of therapy treated with axi-cel experienced better outcomes compared with patients treated with SoC, and that older patients also benefited significantly from axi-cel. These findings suggest that axi-cel addresses an important unmet medical need in patients with r/r FL. Future research should include longer follow-up data on outcomes of axi-cel and CE of axi-cel vs other contemporary SoC therapies.
Real-World Evidence in the United States (US) of the Impact of Bridging Therapy Prior to Axicabtagene Ciloleucel (Axi-Cel) for the Treatment of Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)
Dahiya, Saurabh , Jacobson, Caron A. , Logan, Brent R. , Hu, Zhen‐Huan , Wang, Hailin , Smith, Harry W., Pasquini, Marcelo C. , Cook, Michael Roderick , Shouval, Roni , Perales, Miguel‐Angel , Bezerra, Evandro D. , Niu, Alex , Nastoupil, Loretta J. , Budde, Lihua E. , Olson, Amanda L , Luo, Zhong‐Cheng , Kim, Jaeyeon , Lee, Andrew , Sun, Fang , Locke, Frederick L.

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 103-103

10.1182/blood-2023-175034 Get It

Introduction: Axi-cel utilization expanded after demonstration of superior event-free survival in patients (pts) with early relapsed or primary refractory LBCL (Locke, et al. NEJM. 2022) and was reinforced by improved overall survival (OS) among these pts (Westin, et al. NEJM. 2023). Despite increased demand, limited data exist on the impact of bridging therapies (BT) on pt outcomes. Thus, BT use between leukapheresis and lymphodepletion (LD) is largely at the discretion of treating physicians. Here, we assessed the impact of BT on effectiveness and safety outcomes after axi-cel. Methods: Pts receiving axi-cel for 3L+ LBCL in the US between 2017-2020 were prospectively collected through the CIBMTR registry in a post-authorization safety study; data up to May 2023 were included. Effectiveness outcomes were overall response rate (ORR), complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and OS. Safety outcomes were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT grading, non-relapse mortality (NRM), and other key adverse events. Propensity score-based inverse probability of treatment weighting (IPTW) was used in logistic and Cox regressions to account for potential confounding in BT use. For pts who had BT, effects of BT types and responses on outcomes were evaluated using conventional logistic and Cox regressions. Results: Of 1497 pts registered, 1307 had BT data available and were included (median follow-up, 36 mo). Overall, 430 pts (33%) received BT (median time from leukapheresis to LD, 23 days [IQR, 21-28]). Systemic therapy was used in 403 pts (31%), including 305 (23%) with chemotherapy (CT)-based BT (19% treated with CT + anti-CD20 monoclonal antibody [mAb; mainly rituximab] and 4% with CT only), and 98 (7%) with non-CT systemic therapy (Table). Radiotherapy (± systemic therapy) was used in 44 pts (3%). Pts with ≥3 lines of prior therapy (odds ratio [OR], 10.67 [95% CI, 7.17−15.87]) or mild hepatic impairment prior to infusion (OR, 1.64 [1.06−2.55]) were more likely to receive BT, while those with histologic transformation (OR, 0.69 [0.51−0.92]) or longer time from diagnosis to leukapheresis were less likely to receive BT. ORRs to axi-cel were 70% and 79% (CR rates 51% and 64%) for pts with or without BT, respectively. Unadjusted DOR, PFS, and OS at 3 years were 40%, 28%, and 37%, respectively, in pts with BT vs 49%, 39%, and 49%, respectively, in those without BT. After multivariate adjustment, no statistical significance was found between BT and any effectiveness outcome. Adjusted hazard ratios (HRs) for BT were 1.13 (95% CI, 0.94-1.36) for PFS and 1.11 (95% CI, 0.92-1.34) for OS, respectively (Figure). Most safety endpoints were consistent regardless of BT. Grade ≥3 CRS and ICANS occurred in 12% and 30% of pts, respectively, who received BT vs 10% and 24% of pts who did not. Use of BT was associated with more frequent prolonged neutropenia (OR, 2.24 [1.44-3.50]) and thrombocytopenia (OR, 2.33 [1.67-3.24]), but not associated with a higher rate of infections or NRM (Table). Among pts receiving BT, 74 (17%) had a CR or partial response to BT. Of them, median PFS and median OS post infusion were 12.7 mo (3.8-not estimable [NE]) and 48.7 mo (18.6-NE), respectively. Response to BT was associated with increased CR rate (OR, 2.00 [1.07-3.75]), PFS (HR, 0.69 [0.49-0.99]), and OS (HR, 0.59 [0.40-0.88]) and decreased any-grade ICANS (OR, 0.51 [0.29-0.92]). When different BT strategies were considered, effectiveness and most safety outcomes for CT + anti-CD20 mAb vs non-CT treatment were comparable without significant difference. CT + anti-CD20 mAb was associated with improved ORR (OR, 1.90 [1.00-3.60]), PFS (HR, 0.69 [0.49-0.98]), and OS (HR, 0.66 [0.46-0.95]) but increased any-grade CRS (OR, 2.16 [1.02-4.57]) vs CT only. CT use was associated with an increased risk of prolonged thrombocytopenia (41% vs 24% for pts receiving non-CT treatment; OR, 2.37 [1.39-4.02]). No significant association was found between use of radiotherapy as BT and any outcome. Conclusion: These US real-world findings suggest that the addition of BT prior to axi-cel is associated with more frequent prolonged cytopenias but does not impact effectiveness or other critical safety outcomes. Response to BT may prognosticate more favorable outcomes after axi-cel infusion. Further study is warranted to identify the optimal bridging regimen.
Outcomes of Axicabtagene Ciloleucel in Comparison with Chemoimmunotherapy (CIT) in an Elderly Population for Treatment of Relapsed or Refractory (r/r) Large B-Cell Lymphoma (LBCL) after Two or More Lines of Prior Therapy
Lunning, Matthew A. , Wang, Hailin , Hu, Zhen‐Huan , Jacobson, Caron A. , Lin, Yi , Hill, Brian T. , Neelapu, Sattva S. , Miao, Harry , Shahani, Shilpa, Patel, Anik R. , Spooner, Clare, Fu, Christine, Xu, Hairong, Pasquini, Marcelo C. , Locke, Frederick L. , Siddiqi, Tanya , Ahmed, Sairah , Miklos, David B. , Ghobadi, Armin , Westin, Jason R.

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 1852-1855

10.1182/blood-2022-162421 Get It

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML
Menghrajani, Kamal , Gomez-Arteaga, Alexandra , Madero‐Marroquin, Rafael , Zhang, Mei‐Jie , Bo-Subait, Khalid, Sánchez, J. Ortiz, Wang, Hailin , Aljurf, Mahmoud , Assal, Amer , Bejanyan, Nelli , Bredeson, Christopher , Byrne, Michael , Castillo, Paul , Černý, Jan , Ciurea, Stefan O. , DeFilipp, Zachariah , Farhadfar, Nosha , Gadalla, Shahinaz M. , Ganguly, Siddhartha , Gowda, Lohith , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Kanakry, Christopher G. , Khimani, Farhad , Krem, Maxwell M. , Liu, Hongtao , Martino, Rodrigo , Michelis, Fotios V. , Nathan, Sunita , Rizzieri, David A. , Rowe, Jacob M. , Seo, Sachiko , Sharma, Akshay , Solh, Melhem , Üstün, Celalettin , Verdonck, Leo F. , Litzow, Mark R. , Weisdorf, Daniel J. , Zhang, Yanming , Tallman, Martin S. , Saber, Wael , Bacher, Ulrike , Bejanyan, Nelli , Bhatt, Vijaya Raj , Cerny, Jan , Chhabra, Saurabh , DeFilipp, Zachariah , Gadalla, Shahinaz M , Gale, Robert P , Hashmi, Shahrukh K , Hildebrandt, Gerhard C , Kansagra, Ankit , Krem, Maxwell M , Lazarus, Hillard M , Liu, Hongtao , Martino, Rodrigo , Michelis, Fotios V , Nishihori, Taiga , Olsson, Richard F , Reshef, Ran , Rizzieri, David A , Savani, Bipin N , Seo, Sachiko , Sharma, Akshay , Ustun, Celalettin , Hourigan, Christopher S , Sandmaier, Brenda M , Litzow, Mark R. , Weisdorf, Dan , Assal, Amer , Badawy, Sherif M. , Bhatt, Vijaya Raj , Chhabra, Saurabh , Gale, Robert Peter , Grunwald, Michael R. , Kansagra, Ankit , Lazarus, Hillard M. , Nishihori, Taiga , Olsson, Richard F. , Reshef, Ran , Savani, Bipin N. , Hourigan, Christopher S. , Kebriaei, Partow

Blood Advances | September 22, 2021 | Volume: 6 | Issue: 3 | Pages: 828-847

10.1182/bloodadvances.2021004881 Get It

Abstract Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
Wieduwilt, Matthew J. , Metheny, Leland , Zhang, Mei‐Jie , Wang, Hailin , Estrada‐Merly, Noel, Marks, David I. , Al‐Homsi, A. Samer, Muffly, Lori , Chao, Nelson J. , Rizzieri, David A. , Gadalla, Shahinaz M. , Cairo, Mitchell S. , Gore, Steven D. , Patel, Sagar S. , Michelis, Fotios V. , Inamoto, Yoshihiro , Copelan, Edward A. , Palmisiano, Neil , Kharfan‐Dabaja, Mohamed A. , Ganguly, Siddhartha , Bredeson, Christopher , Ballen, Karen K. , Martino, Rodrigo , Wirk, Baldeep , Aljurf, Mahmoud , Bashey, Asad, Murthy, Hemant S. , Farhadfar, Nosha , Liu, Hongtao , Abdel‐Azim, Hisham , Solh, Melhem , Seftel, Matthew D. , Poel, Marjolein van der , Kamble, Rammurti T., Munker, Reinhold , Cahn, Jean‐Yves , Freytes, César O. , Krem, Maxwell M. , Winestone, Lena E. , Nathan, Sunita , Verdonck, Leo F. , Sharma, Akshay , Ringdén, Olle , Černý, Jan , Choe, Hannah , Seo, Sachiko , Baxter‐Lowe, Lee Ann , Hildebrandt, Gerhard , Litzow, Mark R. , Abid, Muhammad Bilal , Weisdorf, Daniel J. , Saber, Wael , Chao, Nelson , Rizzieri, David A , Gadalla, Shahinaz M , Bhatt, Vijaya Raj , Patel, Sagar , Michelis, Fotios V , Kharfan-Dabaja, Mohamed A , Savani, Bipin N , Martino, Rodrigo , Bacher, Ulrike , Liu, Hongtao , Waller, Edmund K , McGuirk, Joseph , Krem, Maxwell M , Winestone, Lena E , Olsson, Richard F , Sharma, Akshay , Ringden, Olov , Friend, Brian D , Cerny, Jan , Chhabra, Saurabh , Nishihori, Taiga , Seo, Sachiko , George, Biju , Baxter-Lowe, Lee Ann , Hildebrandt, Gerhard C , de Lima, Marcos , Litzow, Mark R. , Hourigan, Christopher S , Weisdorf, Dan , Murthy, Hemant S , Muffly, Lori , Abid, Muhammad Bilal , Gale, Robert Peter , Mussetti, Alberto , Bhatt, Vijaya Raj , Badawy, Sherif M. , Lazarus, Hillard M. , Díaz, Miguel Ángel , Cassaday, Ryan D. , Savani, Bipin N. , Yared, Jean A. , Aldoss, Ibrahim , Waller, Edmund K. , Grunwald, Michael R. , Liesveld, Jane L. , McGuirk, Joseph P. , Lee, Jong Wook , Gergis, Usama , Olsson, Richard F. , Chhabra, Saurabh , Nishihori, Taiga , Lima, Marcos de , Kebriaei, Partow , Hourigan, Christopher S.

Blood Advances | September 21, 2021 | Volume: 6 | Issue: 1 | Pages: 339-357

10.1182/bloodadvances.2021004916 Get It

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
Comparison of Haploidentical Donor Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide to Matched-Sibling, Matched-Unrelated, Mismatched-Unrelated, and Umbilical Cord Blood Donor Transplantation in Adults with Acute Lymphoblastic Leuk
Wieduwilt, Matthew J. , Metheny, Leland , Zhang, Mei‐Jie , Wang, Hailin , Estrada‐Merly, Noel, Litzow, Mark R. , Hourigan, Chris S., Saber, Wael , Lima, Marcos de , Kebriaei, Partow , Hourigan, Christopher S. , Weisdorf, Daniel J.

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 50-51

10.1182/blood-2020-137186 Get It

Background The relative benefits of haploidentical HCT using PTCy compared to traditional matched-sibling donor, traditional unrelated donor and umbilical cord blood (UCB) allogeneic HCT for adult acute lymphoblastic leukemia (ALL) is still being defined. Methods We performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database comparing post-HCT outcomes of haploidentical donors with PTCy to HLA-identical sibling donors, 8/8 HLA-MUDs, 7/8 HLA-MUDs, and UCB. Outcomes were overall survival (OS) leukemia-free survival (LFS), relapse, non-relapse mortality (NRM), grade 2-4 and grade 3-4 acute graft-versus-host disease (aGVHD), and chronic GVHD (cGVHD). Eligible patients were adults with ALL in complete remission (CR1, CR2, or CR3) undergoing first allogeneic HCT from 2013 to 2017. Key exclusion included not receiving PTCy for haploidentical HCT and ex vivo T-cell depleted or CD34-selected grafts. Cox proportional hazards multivariable regression analysis was used to compare the treatment groups. Results 4201 patients were studied: 393 haploidentical donor (92 centers), 1627 HLA-identical sibling donor (206 centers), 1646 8/8 HLA-MUD (181 centers), 230 7/8 HLA-MUD (90 centers), and 305 UCB (79 centers). Groups were well matched, however, notable differences between included race, time from diagnosis to HCT (CR1 only), conditioning regimen intensity, donor age, graft source for non-cord (peripheral blood or bone marrow), GVHD prophylaxis modality, and the use of in vivo T-cell depletion. Compared to other groups, haploidentical HCT had the lowest percentage of non-Hispanic white patients (43% vs. 49-74%), was more likely to use reduced-intensity conditioning (42% vs 17-25%), and was more likely to use bone marrow (41% vs. 14-29%). In multivariate analysis comparing haploidentical to matched-sibling donor HCT, no differences were observed in OS, LFS, NRM, relapse, or aGVHD. Compared to haploidentical HCT, the risk of cGVHD was significantly higher with matched-sibling donor HCT (D/R sex match F/M, HR 2.59, P<0.001, D/R sex match, other, HR 1.37, P=0.003). Comparing haploidentical to 8/8 HLA-MUD HCT, no differences were seen in OS, LFS, relapse, or Grade 2-4 aGVHD but 8/8 HLA-MUD HCT was associated with increased incidences of NRM (HR 1.42, P=0.02), grade 3-4 aGVHD (HR 1.59, P=0.005), and cGVHD (HR D/R sex match F/M, HR 2.91, P<0.001, D/R sex match, other, HR 1.38, P=0.001). Comparing haploidentical to 7/8 HLA-MUD HCT, no differences were seen in LFS or relapse but 7/8 HLA-MUD HCT was associated with worse OS (HR 1.38, P=0.01) and increased incidences of NRM (HR 2.13, P=<0.001), grade 2-4 aGVHD (HR 1.33, P=0.04) , grade 3-4 aGVHD (HR 1.86, P=0.003), and cGVHD (HR 1.72, P=<0.001). Comparing haploidentical to UCB HCT, no differences were seen in late OS (>18 months), late LFS, relapse, or cGVHD. Compared to haploidentical HCT, UCB HCT was associated with worse early OS (≤18 months, HR 1.93, P<0.001), worse early LFS (HR 1.40, P=0.007) and increased incidences of NRM (HR 2.08, P<0.001), grade 2-4 aGVHD (HR 1.83, P<0.001), and grade 3-4 aGVHD (HR 1.97, P<0.001). Similar outcomes were observed in sensitivity analyses restricting cohorts to (1) MA conditioning with peripheral blood stem cells and (2) calcineurin inhibitor-based GVHD prophylaxis for matched-sibling, unrelated donor, and UCB HCT. Conclusions For OS and LFS, haploidentical HCT using PTCy for adult ALL was superior to traditional HCT using 7/8 HLA-MUDs and UCB but equivalent to traditional HCT using matched-sibling donors and 8/8 HLA-MUDs. Results were consistent across all subgroups. Haploidentical HCT had a lower incidence of aGVHD compared to 8/8 HLA-MUD, 7/8 HLA-MUD, and UCB HCT and a lower incidence of cGVHD compared to matched-sibling donor, 8/8 HLA-MUD, and 7/8 HLA-MUD HCT. Based on these data, haploidentical HCT with PTCy results in similar survival with less GVHD compared to traditional matched-sibling and 8/8 HLA-matched donor HCT and is the superior alternative donor option for adult patients with ALL needing allogeneic HCT in CR. Figure Disclosures Wieduwilt: Leadiant: Research Funding; Shire: Research Funding; Merck: Research Funding; Macrogeneics: Research Funding; Amgen: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. de Lima:Incyte: Other: Personal Fees, advisory board; BMS: Other: Personal Fees, advisory board; Pfizer: Other: Personal fees, advisory board, Research Funding; Celgene: Research Funding; Kadmon: Other: Personal Fees, Advisory board. Kebriaei:Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Amgen: Other: Research Support; Jazz: Consultancy. Hourigan:Merck: Other: Research Support (CRADA); Sellas: Other: Research Support (CRADA). Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding.
Allogeneic Hematopoietic Stem Cell Transplantation for Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemia
Metheny, Leland , Saber, Wael , Litzow, Mark R. , Hall, Aric C. , Zhang, Mei‐Jie , Wang, Hailin , Bo-Subait, Khalid, Weisdorf, Daniel J. , Lima, Marcos de , Callander, Natalie S. , Kebriaei, Partow , Sandmaier, Brenda M

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 2036-2036

10.1182/blood-2019-125946 Get It

Patients who develop therapy-related myelodysplastic syndromes (t-MDSs) or acute myeloid leukemia (t-AML) following prior chemotherapy or an autologous hematopoietic cell transplant (HCT), have a poor prognosis. An earlier analysis of allogeneic HCT (n=868, 1990-2004) showed 5-year overall survival (OS) and disease free survival (DFS) were 22% and 21% (reference). Furthermore, older age, graft source other than a HLA-matched sibling or HLA well matched unrelated donor (URD), t-AML not in remission or advanced t-MDS, and poor risk cytogenetics were associated with worse outcomes. Modern supportive care and conditioning regimens including reduced intensity (RIC) regimens may have improved outcomes. Therefore we analyzed 1531 HCT for t-AML (n = 772) or t-MDS (n = 759) performed from 2000 to 2014. The median age at transplant was 52 (18-77) for t-AML and 59 (18-74) for t-MDS. Eleven percent of patient with t-AML and 24% of patient with t-MDS had a prior autologous transplant. A myeloablative regimen was used for conditioning in 61% of patients with t-AML and 49% of patients with t-MDS (Table 1). For t-AML, the 5-year non-relapse mortality (NRM) and relapse rates (RR) were 33% (95% confidence interval [CI], 30-36) and 43% (40-47), respectively. For t-MDS, the 5 year TRM and RR were 32% (29-36) and 46% (43-50), respectively. Five year DFS and OS were 24% (21-27) and 25% (22-28), respectively, for patients with t-AML. Five year DFS and OS were 21% (18-24) and 27% (23-31), respectively, for patients with t-MDS. In multivariate analysis, t-AML OS and DFS was worse for: previous autologous transplant, relapsed disease at HCT, intermediate or adverse cytogenetics, partially matched and cord blood grafts, and RIC. For t-MDS: age greater than 60, previous autologous transplant, very high IPSS score, and use of HLA-partially matched unrelated grafts. A significant minority of patients with t-AML and t-MDS can achieve long-term remission with allogeneic HCT, yet risks of both NRM and relapse are still excessive. Relapse is the major cause of treatment failure. Disclosures Metheny: Takeda: Speakers Bureau; Incyte: Speakers Bureau. Weisdorf:Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy. Kebriaei:Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria; Kite: Honoraria.
Myeloablative Conditioning Is Preferred for Allogeneic Transplantation of Acute Myeloid Leukemia and Myelodysplastic Syndromes with Low/Intermediate but Not High Disease Risk Index
Bejanyan, Nelli , Zhang, Mei‐Jie , Bo-Subait, Khalid, Wang, Hailin , Warlick, Erica D. , Brunstein, Claudio G. , Litzow, Mark R. , Saber, Wael , Sandmaier, Brenda M , Kebriaei, Partow , Weisdorf, Daniel J.

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 4603-4603

10.1182/blood-2019-123513 Get It

Although some data (Scott, JCO 2017) suggest that myeloablative conditioning (MAC) is preferred for allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), these data were not informed by analysis of disease specific risk factors. We analyzed AML and MDS HCT outcomes stratified by the disease risk index (DRI) in order to identify the preferred transplant conditioning intensity (reduced-intensity conditioning [RIC] vs. MAC). In this large CIBMTR registry study we identified 4387 adult patients (age 40-65 years) who received HCT for AML (68%) or MDS (32%) between 2009 and 2015. DRI was stratified as low/ intermediate risk (1539 MAC and 999 RIC) and high/ very high risk (1121 MAC and 728 RIC). Examining the low/ intermediate risk DRI cohort (Table), RIC was associated with lower risk of TRM (HR=0.74, 95% CI 0.62-0.88; p<0.001) but significantly higher risk of relapse (HR=1.54, 95% CI 1.35-1.76; p<0.001). As a result, RFS in this cohort was significantly worse with RIC (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/ very high risk DRI cohort, RIC resulted in similar TRM (HR=0.83, 95% CI 0.68-1.00; p=0.051) but again significantly higher risk of relapse (HR=1.23, 95% CI 1.08-1.41; p=0.002). RFS in high/ very high risk DRI cohort was similar between RIC and MAC. Adjusted outcome curves for the 3 endpoints are shown in the Figure. In this large study of HCT for AML or MDS stratified by DRI, RIC was independent predictor of lower TRM, but significantly higher risk of relapse. The MAC was an independent predictor of lower relapse in both low/ intermediate and high/very high DRI groups. However, MAC only resulted in RFS benefit in the low/ intermediate group where the magnitude of impact on relapse was not offset by the higher TRM. In adults with AML or MDS aged 40-65 years, these data support MAC as the preferred conditioning intensity for low/ intermediate risk DRI, whereas MAC does not provide significant benefit in those with high/ very high risk DRI. Safer, yet still potent MAC regimens could benefit this higher risk group. Disclosures Bejanyan: Kiadis Pharma: Other: advisory board. Brunstein:Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria; Pfizer: Honoraria; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.