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35 citation(s) found for "Ganguly, Siddhartha".

Impact of Allogeneic Hematopoietic Cell Transplantation (HCT) As Consolidation Following CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for Treatment of Relapsed Acute Lymphoblastic Leukemia (ALL)
Park, Jae H. , Nikiforow, Sarah , Hu, Zhen‐Huan , Bredeson, Christopher , Brown, Valerie I. , Cairo, Mitchell S. , Dholaria, Bhagirathbhai , Ganguly, Siddhartha , Hanna, Rabi , Kohorst, Mira A. , Lekakis, Lazaros J. , Rizzieri, David A. , Savani, Bipin B., Thakar, Monica S. , Wagner, John L. , Qiu, Xianmiao, Pasquini, Marcelo C. , Dholaria, Bhagirathbhai R , Kim, Soyoung , Moskop, Amy , Ahmed, Sairah , Abid, Muhammad Bilal , Badar, Talha , Díaz, Miguel Ángel , Grover, Natalie S. , Hematti, Peiman , Lazarus, Hillard M. , Locke, Frederick L. , Murthy, Hemant S. , Mussetti, Alberto , Pulsipher, Michael A. , Qayed, Muna , Reshef, Ran , Salas, María Queralt , Sharma, Akshay , Schultz, Kirk R. , Turtle, Cameron J. , Yared, Jean A. , Perales, Miguel‐Angel

Mayo Clinic

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 3880-3880

10.1182/blood-2021-148652 Get It

Abstract Background: CD19 CAR T cell therapies have demonstrated high initial complete remission (CR) rates of 70-80% in relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with durable remissions observed in a subset of patients. Despite the remarkable initial CR rate, relapses occur in 20-45% of patients and with increasing use of CD19 CAR T cell therapies in ALL, a key remaining clinical question is the role of post-CAR HCT. Methods: Patients up to 26 years treated with the commercial (i.e., tisagenlecleucel) or investigational CD19 CAR T cell products from 2014 to 2019 in the United States were included. The objectives were to examine the impact of post-CAR HCT on mortality, disease-free survival (DFS), leukemia relapse, GVHD and transplant related mortality among HCT recipients. The intent of HCT was analyzed as consolidation when there was no evidence of post-CAR T cell relapse prior to HCT. Cox regression multivariable analysis used HCT as time-dependent variable along with age, performance status and time from diagnosis to CAR-T cell infusion to evaluate its impact on outcomes. Results: We identified 347 patients who received CD19 CAR T cells from 86 centers. Median age was 13 (range, 0.4-26 years) with 39% of patients from Hispanic or Latino ethnic origin. Patients were high risk and heavily pretreated; 56% had poor cytogenetics, 51% had ≥3 line of prior therapies and 34% had prior HCT. Most of the patients (74%) received tisagenlecleucel. Disease burden at the time of CAR T cell infusion included morphologic disease (≥5% bone marrow blasts) (65%), measurable residual disease (MRD) positive (16%) and negative CR (18%). CRS of all grades was observed in 57.6% and grade 3-4 CRS in 13%; neurotoxicity of all grades was observed in 25% and grade 3-4 in 8%. With a median follow-up of 12.7 months (range, 2.2-60.3), DFS at 3, 6 and 12 months following CAR T cell infusion was 80.9% % (95% CI: 76.6%-84.9%), 71.2% (95% CI: 66.1%-76.0%) and 57.6% (95% CI: 51.8%-63.3%), respectively. OS at 3, 6 and 12 months was 93.6% (95% CI: 90.8%-96.0%), 89.8% (95% CI: 86.4%-92.8%) and 79.4% (95% CI: 74.7%-83.6%), respectively. Incidences of relapse without censoring at subsequent HCT at month 3, 6 and 12 were 18.5% (95% CI: 14.5%-22.8%), 28.2% (95% CI: 23.5%-33.3%), and 40.6% (95% CI: 35.0%-46.3%), respectively. Of the 347 patients who received CD19 CAR therapy, 62 patients (18%) had subsequent HCT in CR as a consolidation post-CAR with a median time from CAR T to HCT of 4.7 months (range, 1.1-18.6). 36% had a prior HCT (i.e., pre-CAR), 87% received myeloablative regimen and among the 57 patients with MRD evaluation 56 were negative (98%). Frequencies of post-CAR HCT did not change during the 5-year study period. Overall, transplant related mortality (TRM) at month 6 was 8.9% (95% CI: 3.6-16.1), and grade 2-4 acute GvHD was observed in 38.0% (95% CI: 28.4-48.2) of patients at month 6. Post-CAR HCT used as a consolidation was associated with lower relapse (hazard ratio (HR) 0.37; p=0.037) but no significant impact on mortality (HR 0.75, p=0.51) or DFS (HR=0.46, p=0.057). When accounting for any HCT performed after CAR T cell, HCT was associated with higher mortality (Figure). Conclusions: This is the largest clinical series to date examining the impact of post-CAR HCT on clinical outcome of R/R B-ALL patients. We found that 18% of the patients had post-CAR HCT as a consolidation therapy with a favorable safety profile of 8.9% TRM rate despite a prior transplant rate of 36%. Consolidation HCT after CAR T cell resulted in significant reduction in leukemia relapse with a trend towards better DFS. Consolidation HCT seem safe and incurred a benefit by reducing disease relapse. Further studies in understanding the role of consolidation HCT as planned, or post-CAR T cell response-based strategy or treatment for early B-cell recovery are needed to further define the best candidates for HCT after tisagenlecleucel . Figure 1 Figure 1. Disclosures Park: BMS: Consultancy; Affyimmune: Consultancy; Kite Pharma: Consultancy; Curocel: Consultancy; Novartis: Consultancy; Minerva: Consultancy; Innate Pharma: Consultancy; PrecisionBio: Consultancy; Intellia: Consultancy; Amgen: Consultancy; Autolus: Consultancy; Servier: Consultancy; Artiva: Consultancy; Kura Oncology: Consultancy. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Ahmed: Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Xencor: Research Funding. Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Cairo: Servier: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Nektar: Membership on an entity's Board of Directors or advisory committees. Dholaria: Janssen: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Pfizer: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Grover: Kite: Other: Advisory Board; Genentech: Research Funding; ADC: Other: Advisory Board; Tessa: Consultancy; Novartis: Consultancy. Locke: Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Novartis: Consultancy, Other, Research Funding; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Takeda: Consultancy, Other; EcoR1: Consultancy; Cowen: Consultancy; Umoja: Consultancy, Other; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding. Murthy: CRISPR Therapeutics: Research Funding. Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Pulsipher: Jasper Therapeutics: Honoraria; Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees. Qayed: Novartis: Membership on an entity's Board of Directors or advisory committees; Medexus: Membership on an entity's Board of Directors or advisory committees; Mesoblast: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; BMS: Other. Reshef: Gilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Gilead and Novartis: Honoraria; Bayer, BMS, Regeneron, TScan, Synthekine, Atara, Jasper: Consultancy. Rizzieri: Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acrotech: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria; Pharmacyclics: Honoraria. Sharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Vindico Medical Education: Honoraria; Spotlight Therapeutics: Consultancy; Novartis: Other: Salary support paid to institution. Schultz: BMS DSMB: Other: payment; Sobi: Membership on an entity's Board of Directors or advisory committees. Turtle: Century Therapeutics Ad hoc advisory boards (last 12 months): Nektar Therapeutics, Allogene, PACT Pharma, Astra Zeneca, Amgen: Membership on an entity's Board of Directors or advisory committees; Precision Biosciences: Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences: Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees; ArsenalBio: Membership on an entity's Board of Directors or advisory committees; Minerva: Other; Nektar Therapeutics: Other; Juno Therapeutics/BMS: Other: Payments, Patents & Royalties: Patent licensed to Juno Therapeutics.; Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, ArsenalBio: Current holder of stock options in a privately-held company. Pasquini: Kite Pharma: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Perales: MorphoSys: Honoraria; Cidara: Honoraria; Bristol-Myers Squibb: Honoraria; Miltenyi Biotec: Honoraria, Other; Sellas Life Sciences: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Omeros: Honoraria; Nektar Therapeutics: Honoraria, Other; Equilium: Honoraria; Novartis: Honoraria, Other; NexImmune: Honoraria; Incyte: Honoraria, Other; Kite/Gilead: Honoraria, Other; Merck: Honoraria; Servier: Honoraria; Medigene: Honoraria.
Autologous transplant vs chimeric antigen receptor T-cell therapy for relapsed DLBCL in partial remission
Shadman, Mazyar , Pasquini, Marcelo C. , Ahn, Kwang Woo , Chen, Yue , Turtle, Cameron J. , Hematti, Peiman , Cohen, Jonathon B. , Khimani, Farhad , Ganguly, Siddhartha , Munshi, Pashna N. , Beitinjaneh, Amer , Herrera, Alex F. , Sauter, Craig S. , Kharfan‐Dabaja, Mohamed A. , Pasquini, Marcelo , Herrera, Alex F , Kharfan-Dabaja, Mohamed A , Hamadani, Mehdi , Shadman, Mazyar , Hematti, Peiman , Turtle, Cameron J , Merryman, Reid W. , Yared, Jean A. , Locke, Frederick L. , Ahmed, Nausheen , Reagan, Patrick Michael , Hamadani, Mehdi

Mayo Clinic

Blood | September 27, 2021 | Volume: 139 | Issue: 9 | Pages: 1330-1339

10.1182/blood.2021013289 | PMID 34570879 Get It

Abstract The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.
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

Mayo Clinic

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

10.1182/bloodadvances.2021004881 | PMID 34551064 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.

Mayo Clinic

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

10.1182/bloodadvances.2021004916 | PMID 34547770 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.
Real-world evidence of axicabtagene ciloleucel (Axi-cel) for the treatment of large B-cell lymphoma (LBCL) in the United States (US).
Jacobson, Caron A. , Hu, Zhen‐Huan , Miklos, David B. , Lunning, Matthew A. , Hill, Brian T. , Ganguly, Siddhartha , Dong, Hua, Nikiforow, Sarah , Xie, Jing , Xu, Hairong , Hooper, Michele, Kawashima, Jun , Pasquini, Marcelo C. , Miklos, David B , Locke, Frederick L. , Siddiqi, Tanya , Ahmed, Sairah , Ghobadi, Armin , Lin, Yi , Perales, Miguel‐Angel , Herr, Megan M.

Mayo Clinic

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7552-7552

10.1200/jco.2021.39.15_suppl.7552 Get It

7552 Background: Axi-cel is approved in the US for the treatment of adult patients with relapsed or refractory LBCL after 2 or more lines of systemic therapy. Post-market long term follow up study of commercial Axi-cel recipients using the Center for International Blood and Marrow Transplant Research was recently completed. Methods: From October 2017 to August 2020, 1,500 Axi-cel recipients from 79 centers were enrolled. Of these, 1001 patients with at least 6 months of follow-up were included in this analysis. Outcomes include complete and overall responses rates (CR and ORR), duration of response (DOR), progression-free and overall survival (PFS and OS), cytokine release syndrome (CRS) (Lee D 2014 and American Society for Transplantation and Cellular Therapy [ASTCT]), immune effector cell associated neurotoxicity syndrome (ICANS), hematologic recovery and subsequent neoplasm (SN). Subgroup analysis by sensitivity to therapy, defined as responsive to the last line of therapy prior to Axi-cel. Median follow-up was 12 months (range, 6-28 months). Results: The median age overall was 62 years, 37% were ≥ 65 years, 83% with Eastern Cooperative Oncology Group (ECOG) performance score 0-1, 28% with transformed lymphoma, 14% with high grade lymphoma, 29% with prior autologous transplant, and 66% with chemotherapy-resistant disease prior to Axi-cel. The median time from diagnosis to Axi-cel infusion was 15 months. Best ORR was 70% (CR 53%). Landmark analysis of patients in CR at 6 months post Axi-cel demonstrates a low number of subsequent progression/death events. With respect to outcomes for chemotherapy-sensitive disease versus resistant disease, the ORR, CR, 12-month PFS and OS were 78% vs. 66%, 60% vs. 48%, 55% (95% CI, 48-62%) vs. 40% (95% CI, 37-44%), and 70% (95% CI, 63-76%) vs. 54% (95% CI, 50-58%), respectively. CRS of any grade was reported in 83% of patients. Incidence of Grades ≥ 3 CRS was 10% according to Lee et al 2014, and 13% according to ASTCT Consensus Grading. Median time to any grade CRS was 4 days (range, 1-28 days), and 93% of CRS cases resolved with a median duration of 7 days (range, 1-121 days). ICANS were reported in 576 (57%) patients, grade >3 was 26%. The median time to onset of ICANS was 7 days (range, 1-82 days), and 86% resolved with a median duration of 9 days (range, 1 to 115 days). Twenty-nine patients (2.9%) reported SN: hematologic (N = 17), solid tumors (N = 12). Conclusions: This is the largest report on Axi-cel in the real-world setting and demonstrates consistent efficacy outcomes and further characterizes safety outcomes. Patients in CR at 6 months have sustained disease control with low number of relapse events. Although patients with therapy-sensitive disease experience better outcomes than patients with therapy-resistant, the overall outcomes on both groups of patients are favorable.
Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis
Bona, Kira , Brazauskas, Ruta , He, Naya, Lehmann, Leslie , Abdel‐Azim, Hisham , Ahmed, Ibrahim , Al‐Homsi, A. Samer, Aljurf, Mahmoud , Arnold, Staci D. , Badawy, Sherif M. , Beattie, Sara , Dalal, Jignesh , Dandoy, Christopher E. , Frangoul, Haydar , Freytes, César O. , Ganguly, Siddhartha , Hahn, Theresa , Kamble, Rammurti T., LeMaistre, Charles F. , Law, Jason , Majhail, Navneet S. , Preussler, Jaime M. , Schears, Raquel M. , Seo, Sachiko , Sharma, Akshay , Steinberg, Amir , Szwajcer, David , Wirk, Baldeep , Khera, Nandita , Wood, William A. , Hashmi, Shahrukh K. , Duncan, Christine , Saber, Wael , Hashmi, Shahrukh, Majhail, Navneet S , Sharma, Akshay , Badawy, Sherif M , Arnold, Staci D , Dandoy, Christopher E , Wood, William A , Battiwalla, Minoo , Bhatt, Neel S. , Díaz, Miguel Ángel , George, Biju , Gómez‐Almaguer, David , Knight, Jennifer M. , Lazarus, Hillard M. , Olsson, Richard F. , Savani, Bipin N. , Srivastava, Alok , Yoshimi, Ayami

Mayo Clinic

Blood | October 26, 2020 | Volume: 137 | Issue: 4 | Pages: 556-568

10.1182/blood.2020006252 | PMID 33104215 Get It

Abstract Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.
Novel prognostic scoring system for autologous hematopoietic cell transplantation in multiple myeloma
Dhakal, Binod , D’Souza, Anita , Chhabra, Saurabh , Fraser, Raphael , Dávila, Omar, Badawy, Sherif M. , Černý, Jan , Comenzo, Raymond L. , Chakraborty, Rajshekhar , Kamble, Rammurti T., Kharfan‐Dabaja, Mohamed A. , Krem, Maxwell M. , Ganguly, Siddhartha , Janakiram, Murali , Munker, Reinhold , Murthy, Hemant S. , Kumar, Shaji , Shah, Nina , Qazilbash, Muzaffar H. , Chhabra, Saurabh , Comenzo, Raymond , Chakraborty, Rajshekhar , Patel, Sagar , Kumar, Shaji K , D'Souza, Anita , Murthy, Hemant S , Badawy, Sherif M , Janakiram, Murali , Dhakal, Binod , Callander, Natalie S. , Anderson, Kenneth C. , Assal, Amer , Berdeja, Jesús G. , Gale, Robert Peter , Kansagra, Ankit , Patel, Sagar S. , Hari, Parameswaran

Mayo Clinic

British Journal of Haematology | October 23, 2020 | Volume: 191 | Issue: 3 | Pages: 442-452

10.1111/bjh.16987 | PMID 33094839 Get It

AbstractWe studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008–2017 to develop a prognostic model to predict outcomes. High‐risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high‐risk cytogenetics [hazard ratio, (HR) 1·68 (1·3–2·17)] and pre‐AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33–2·12)] were assigned 4 points each; albumin at diagnosis <3·5 g/dl [1·31 (1·07–1·61)] 2; standard risk cytogenetics 1, and no cytogenetics abnormality, BMPCs <10% at AHCT and albumin ≥3·5 g/dl at diagnosis 0 points each. A three‐category system with low risk (0–3), intermediate risk (4–8) and high risk (9–10) showed 3‐year progression‐free survival in the low vs. intermediate vs. high risk of 58% (95% CI: 52–63) vs. 49% (95% CI: 43–56) vs. 31% (95% CI: 12–51), P < 0.001 respectively, and 3‐year OS in low vs. intermediate vs. high risk of 88% (95% CI: 84–91) vs. 81% (95% CI: 76–86) vs. 64% (95% CI: 39–80); P < 0·001. Our prognostic scoring system can identify MM patients at risk for early relapse after AHCT.
Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States
Hong, Sanghee , Brazauskas, Ruta , Hebert, Kyle, Ganguly, Siddhartha , Abdel‐Azim, Hisham , Beattie, Sara , Ciurea, Stefan O. , Szwajcer, David , Badawy, Sherif M. , Gratwohl, Aloïs , LeMaistre, Charles F. , Aljurf, Mahmoud , Farhadfar, Nosha , Seo, Sachiko , Beitinjaneh, Amer , Sharma, Akshay , Law, Jason , Ulrickson, Matthew L. , Schoemans, Hélène , Černý, Jan , Rizzieri, David A. , Kamble, Rammurti T., Shaw, Bronwen E. , Khera, Nandita , Wood, William A. , Hashmi, Shahrukh K. , Hahn, Theresa , Lee, Stephanie J. , Rizzo, J. Douglas , Majhail, Navneet S. , Saber, Wael , Ciurea, Stefan O , Farhadfar, Nosha , Savani, Bipin N , Shaw, Bronwen E , Khera, Nandita , Hashmi, Shahrukh K , Majhail, Navneet S , Sharma, Akshay , Badawy, Sherif M , Lee, Stephanie J , Wood, William A , Díaz, Miguel Ángel , Olsson, Richard F. , Bhatt, Neel S. , Yared, Jean A. , Yoshimi, Ayami , Gergis, Usama , Lazarus, Hillard M. , Hashem, Hasan , Savani, Bipin N.

Mayo Clinic

Cancer | October 21, 2020 | Volume: 127 | Issue: 4 | Pages: 609-618

10.1002/cncr.33232 | PMID 33085090 Get It

BackgroundThe association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.MethodsThis study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014‐2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.ResultsThe median age was 55 years (range, 18‐83 years). The median PCS was –0.21 (range, –1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was –0.13 (range, –1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00‐1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00‐1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02‐1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM.ConclusionsPatients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.
Comparison of outcomes of HCT in blast phase of BCR-ABL1− MPN with de novo AML and with AML following MDS
Kim, Soyoung , Hu, Zhen‐Huan , Aljurf, Mahmoud , Beitinjaneh, Amer , Cahn, Jean‐Yves, Černý, Jan , Copelan, Edward A. , Gadalla, Shahinaz M. , Ganguly, Siddhartha , Hamilton, Betty K. , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Kamble, Rammurti T., Kindwall‐Keller, Tamila L. , Litzow, Mark R. , Rizzieri, David A. , Seo, Sachiko , Solh, Melhem , Verdonck, Leo F. , Wirk, Baldeep , Woolfrey, Ann E. , Alyea, Edwin P. , Sobecks, Ronald , Scott, Bart L. , Nakamura, Ryotaro , Saber, Wael , Hashmi, Shahrukh, Gadalla, Shahinaz M , Kim, Soyoung , Gupta, Vikas , Liu, Ying , Bacher, Ulrike , Cahn, Jean‐Yves , Gale, Robert Peter , George, Biju , Gerds, Aaron T. , Gergis, Usama , Lazarus, Hillard M. , Liesveld, Jane L. , Maziarz, Richard Thomas , Nishihori, Taiga , Olsson, Richard F. , Savani, Bipin N. , Szer, Jeff , Yared, Jean A. , Popat, Uday R

Mayo Clinic

Blood Advances | October 2, 2020 | Volume: 4 | Issue: 19 | Pages: 4748-4757

10.1182/bloodadvances.2020002621 | PMID 33007075 Get It

Abstract Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.
African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States
Badar, Talha , Dávila, Omar, Fraser, Raphael , Wirk, Baldeep , Dhakal, Binod , Freytes, César O. , Valdes, Cesar Rodriguez , Vesole, David H. , Malek, Ehsan , Hildebrandt, Gerhard , Landau, Heather , Murthy, Hemant S. , Meehan, Kenneth R., Solh, Melhem , Kharfan‐Dabaja, Mohamed A. , Farhadfar, Nosha , Kamble, Rammurti T., Vij, Ravi , Munker, Reinhold , Kyle, Robert A. , Hashmi, Shahrukh K. , Ganguly, Siddhartha , Kumar, Shaji , Shah, Nina , D’Souza, Anita , Dhakal, Binod , Malek, Ehsan , Farhadfar, Nosha , Hashmi, Shahrukh K , Jagannath, Sundar , Nieto, Yago , Kumar, Shaji K , Shah, Nina , D'Souza, Anita , Murthy, Hemant S , Badar, Talha , Hari, Parameswaran , Lee, Cindy , Lazarus, Hillard M. , Berdeja, Jesús G. , Díaz, Miguel Ángel , Callander, Natalie S. , Bashir, Qaiser , Chhabra, Saurabh , Jagannath, Sundar , Nishihori, Taiga , Nieto, Yago

Mayo Clinic

Cancer | September 23, 2020 | Volume: 127 | Issue: 1 | Pages: 82-92

10.1002/cncr.33208 | PMID 32966625 Get It

BackgroundMultiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard‐risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent.MethodsThis study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187).ResultsAfrican Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation–Comorbidity Index (HCT‐CI). Fewer African Americans with t(11;14) (21%) had a coexistent high‐risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression‐free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30‐0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT‐CI, and receipt of maintenance.ConclusionsRace may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.