Citations 9
Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis
Murthy, Hemant S. , Zhang, Mei‐Jie , Chen, Karen , Ahmed, Sairah , Ganguly, Siddhartha , Kansagra, Ankit , Michelis, Fotios V. , Nishihori, Taiga , Patnaik, Mrinal M. , Aljurf, Mahmoud , Arai, Yasuyuki , Badar, Talha , Ballen, Karen K. , Bejanyan, Nelli , Brown, Valerie I. , Martino, Rodrigo , Cahn, Jean‐Yves , Castillo, Paul , Černý, Jan , Copelan, Edward A. , Daly, Andrew , Freytes, César O. , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Jamy, Omer , Joseph, Jacinth , Kanakry, Christopher G. , Khera, Nandita , Krem, Maxwell M. , Kuwatsuka, Yachiyo , Lekakis, Lazaros J. , Liu, Hongtao , Modi, Dipenkumar , Munshi, Pashna N. , Palmisiano, Neil , Rizzieri, David A. , Seo, Sachiko , Sharma, Akshay , Sohl, Melhm, Solomon, Scott R. , Ulrickson, Matthew L. , Üstün, Celalettin , Poel, Marjolein van der , Verdonck, Leo F. , Wagner, John L. , Wang, Trent , Wirk, Baldeep , Zeidan, Amer M. , Litzow, Mark R. , Weisdorf, Daniel J. , Saber, Wael , Kharfan‐Dabaja, Mohamed A. , Kansagra, Ankit , Michelis, Fotios V , Nishihori, Taiga , Patnaik, Mrinal , Arai, Yasuyuki , Badar, Talha , Bejanyan, Nelli , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai R , Diaz Perez, Miguel Angel , Freytes, Cesar O , Hashmi, Shahrukh K , Jamy, Omer , Krem, Maxwell M , Lazarus, Hillard M , Liu, Hongtao , Modi, Dipenkumar , Mussetti, Alberto , Patel, Sagar , Shah, Mithun V , Sharma, Akshay , Ustun, Celalettin , Wagner, John , Litzow, Mark R. , Hourigan, Christopher S , Weisdorf, Dan , Kharfan-Dabaja, Mohamed A , Murthy, Hemant S , Martino, Rodrigo , Ahmed, Sairah , Zeidan, Amer M , Deotare, Uday , Abid, Muhammad Bilal , Bacher, Ulrike , Badawy, Sherif M. , Battiwalla, Minoo , Beitinjaneh, Amer , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai , Díaz, Miguel Ángel , Grunwald, Michael R. , Lazarus, Hillard M. , Mussetti, Alberto , Patel, Sagar S. , Shah, Meera , Kebriaei, Partow , Hourigan, Christopher S.
Blood Advances | October 4, 2023 | Volume: 7 | Issue: 22 | Pages: 7007-7016
10.1182/bloodadvances.2023011308
Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.
Comparison of clinical outcomes in patients with relapsed/refractory large B‐cell lymphoma treated with epcoritamab versus chemoimmunotherapy
Mutebi, Alex , Wang, T., Ma, Jun , Wang, A., Yu, Jinhua , Brodkin, Samantha, Kalsekar, Anupama, Ip, Andrew , Rosenthal, Allison , Wang, Trent , Yu, J., Sacchi, M., Muñoz, Javier
Hematological Oncology | June 9, 2023 | Volume: 41 | Issue: S2 | Pages: 433-434
COMPARISON OF THE EFFICACY OF EPCORITAMAB VERSUS CHIMERIC ANTIGEN RECEPTOR THERAPIES, POLATUZUMAB‐BASED REGIMENS, AND TAFASITAMAB‐BASED REGIMENS
Jun, Mira , Wang, T., Mutebi, Alex , Wang, A., Osei-Bonsu, Kojo, Elliott, Brian , Kalsekar, Anupama, Navarro, Fátima, Rosenthal, Allison , Jun, M., Muñoz, Javier , Wang, Trent , Su, Yang , Navarro, F. Rivas, Ip, Andrew
Hematological Oncology | June 9, 2023 | Volume: 41 | Issue: S2 | Pages: 790-792
Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium
Wang, Yucai , Jain, Preetesh , Locke, Frederick L. , Maurer, Matthew J. , Frank, Matthew J. , Muñoz, Javier , Dahiya, Saurabh , Beitinjaneh, Amer , Jacobs, Miriam T. , McGuirk, Joseph P. , Hill, Brian T. , Dorritie, Kathleen , Oluwole, Olalekan O. , Deol, Abhinav , Wang, Trent , Banerjee, Rahul , Miklos, David B. , Rapoport, Aaron P. , Lekakis, Lazaros J. , Neelapu, Sattva S. , Wang, Michael , Munoz, Javier L , Vose, Julie , Goy, Andre Henri , Oluwole, Olalekan O , Deol, Abhinav , Paludo, Jonas , Wang, Trent , Banerjee, Rahul , Miklos, David B , Rapoport, Aaron P , Neelapu, Sattva S , Lin, Yi , Wang, Michael L , Jain, Michael D , Maurer, Matthew , McGuirk, Joseph , Wang, Yucai , Dahiya, Saurabh , Jacobs, Miriam T , Locke, Frederick L , Jain, Preetesh , Vose, Julie M. , Andreadis, Charalambos Babis , Paludo, Jonas , Shah, Bijal , Ghobadi, Armin , Lin, Yi , Jain, Michael D.
Journal of Clinical Oncology | February 8, 2023 | Volume: 41 | Issue: 14 | Pages: 2594-2606
PURPOSE Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication. PATIENTS AND METHODS Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines. RESULTS Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis. CONCLUSION In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
P1155: BREXUCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA IN ROUTINE PRACTICE: UPDATED REPORT FROM THE US LYMPHOMA CAR T CONSORTIUM
Wang, Y., Locke, Fredrick L., Munoz, Jaime O., Dahiya, Saurabh , Jacobs, Michael E. , Vose, JM, Hill, Brian T. , Dorritie, Kathleen , Deol, Abhinav , Wang, T., Neelapu, S.S., Rapoport, Aaron P. , Lekakis, Lazaros J. , Lin, Yu‐Te , Wang, M. , Wang, Yucai , Jain, Preetesh , Maurer, Matthew J. , Frank, Matthew J. , Munoz, J., Beitinjaneh, Amer , McGuirk, Joseph P. , Goy, Andre Henri , Andreadis, Charalambos Babis , Oluwole, Olalekan O. , Shah, Bijal , Paludo, Jonas , Wang, Trent , Banerjee, R., Miklos, David B. , Ghobadi, Armin , Lin, Y., Jain, Michael D.
HemaSphere | June 23, 2022 | Volume: 6 | Issue: No issue available | Pages: 1042-1043
Brexucabtagene Autoleucel for Relapsed/Refractory Mantle Cell Lymphoma: Real World Experience from the US Lymphoma CAR T Consortium
Beitinjaneh, Amer , Frank, Matthew J. , Dahiya, Saurabh , Hill, Brian T. , Oluwole, Olalekan O. , Deol, Abhinav , Wang, Trent , Lekakis, Lazaros J. , Rapoport, Aaron P. , Neelapu, Sattva S. , Wang, Michael , Oluwole, Olalekan O , Wang, Yucai , Jain, Preetesh , Locke, Frederick L. , Muñoz, Javier , Maurer, Matthew J. , McGuirk, Joseph P. , Jacobs, Miriam T. , Goy, Andre Henri , Vose, Julie M. , Shah, Bijal , Paludo, Jonas , Miklos, David B. , Ghobadi, Armin , Lin, Yi , Jain, Michael D.
Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 744-744
Abstract Introduction: Brexucabtagene autoleucel (brexu-cel) was approved by US FDA for relapsed/refractory (R/R) mantle cell lymphoma (MCL) on July 24, 2020 based on results from the pivotal ZUMA-2 (NCT02601313) study, in which an objective response rate (ORR) of 93% and a complete response (CR) rate of 67% were achieved among the 60 treated patients with at least 7 months of follow-up. The study had stringent eligibility criteria, including prior treatment with a BTK inhibitor (BTKi), and only allowed BTKi and/or corticosteroid for bridging therapy. We report here the safety and efficacy of brexu-cel in standard of care practice among centers in the US Lymphoma CAR-T Consortium. Methods: Fourteen centers participated in this retrospective study. Patients who underwent leukapheresis by 6/15/2021 with an intent to manufacture brexu-cel were included. Baseline clinical characteristics, bridging therapy, adverse events after brexu-cel infusion, and post-infusion outcome data were collected. Eligibility for ZUMA-2 was retrospectively determined based on characteristics at the time of leukapheresis. Duration of response (time from initial response to disease progression or death from any cause), progression-free survival (PFS; time from infusion to disease progression or death from any cause) and overall survival (OS; time from infusion to death from any cause) were analyzed using the Kaplan-Meier method. Results: At the data cut-off date of 7/9/2021, 107 patients underwent leukapheresis, among whom 93 (87%) completed brexu-cel infusion, 2 (2%) were waiting for infusion, and 12 (11%) did not receive infusion (manufacture failure n=6, organ dysfunction n=1, death n=5). Baseline clinical characteristics of the 93 infused patients are shown in Table 1. The median age was 67 years and 81% were male. 32% had high risk simplified MIPI, 77% had Ki-67≥30%, 45% had blastoid or pleomorphic variant, 46% had TP53 alteration, 29% had complex karyotype, and 7% had CNS involvement. The median number of prior lines of therapy was 3. Eighty-two percent had prior BTKi treatment, and 44% had refractory disease to the last line of therapy. Sixty-eight (73%) patients would not have met ZUMA-2 eligibility criteria. Reasons for ineligibility included ECOG PS ≥2 (n=8), CNS involvement by lymphoma (n=6), prior therapies (n=33), cytopenia (n=11), renal or hepatic dysfunction (n=13), other medical conditions (n=18), and active infection (n=2). Sixty (65%) of the 93 patients received bridging therapy, which included BTKi (n=27), venetoclax (n=14), chemotherapy (n=19), CD20 antibody (n=26), lenalidomide (n=3), corticosteroid (n=9), and radiotherapy (n=13). Only 13 (14%) patients received BTKi or corticosteroid alone as in ZUMA-2. Among 93 infused patients, cytokine release syndrome (CRS) rate was 88% (8% grade ≥3), and immune effector cell-associated neurotoxicity syndrome (ICANS) rate was 58% (33% grade ≥3). No grade 5 CRS or ICANS occurred. Medications used to manage CRS and ICANS were 71 (76%) for tocilizumab, 64 (69%) for steroid, and 16 (17%) for anakinra. Twenty-four (26%) patients required ICU admission, 9 patients required vasopressors, and 4 patients required mechanical ventilation. With a median follow-up of 3.0 months (range 0.1-9.6), day 30 response was evaluable in 81 patients, and the ORR was 86%, with 64% CR (Table 2). The ORR/CR rates were 94%/70% for blastoid or pleomorphic variants, 82%/50% for TP53 altered, 84%/61% for BTKi-exposed, 94%/76% for BTKi-naïve, and 88%/67% for those not meeting ZUMA-2 eligibility criteria. The ORR/CR rates were 87%/69% for patients who received bridging therapy and 85%/56% for those who did not. For patients who achieved a response at day 30, the rate of continued response at 3-month was 83.7% (95% CI 68.3%-92.0%). The 3-month PFS rate was 80.6% (95% CI 68.6%-88.4%), and the 6-month OS rate was 82.1% (95% CI 67.7%-90.5%). Conclusions: This multicenter retrospective study demonstrated encouraging safety and efficacy data of brexu-cel in R/R MCL in the real world practice. The CRS and ICANS incidences were comparable to those reported in ZUMA-2, but use of tocilizumab and steroid was more frequent than in ZUMA-2. Although 73% of the patients would have been ineligible for ZUMA-2, the ORR and CR rate were comparable to those reported in ZUMA-2. Longer follow-up is necessary to confirm long term safety and efficacy. YW, PJ and FLL are co-first authors, and YL, MW and MDJ are co-senior authors. Figure 1 Figure 1. Disclosures Wang: Novartis: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; InnoCare: Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding. Jain: Kite: Consultancy; Lilly: Membership on an entity's Board of Directors or advisory committees. Locke: Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; EcoR1: Consultancy; Cowen: Consultancy; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Umoja: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Legend Biotech: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: 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. Munoz: Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, and Millennium: Research Funding; Kite, a Gilead Company, Kyowa, Bayer, Pharmacyclics/Janssen, Seagen, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche.: Speakers Bureau; Targeted Oncology, OncView, Kyowa Kirin, Physicians' Education Resource, and Seagen: Honoraria; Pharmacyclics/Abbvie, Bayer, Kite, a Gilead Company, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa Kirin, Alexion, Fosun Kite, Innovent, Seagen, BeiGene, Debiopharm, Epizyme, Karyopharm, ADC Therapeutics, Servier, and Genmab: Consultancy, Other: advisory role; Alexion, AstraZeneca Rare Disease: Other: Study investigator. Maurer: BMS: Research Funding; Genentech: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding. Beitinjaneh: Kite/Gilead: Other: Ad Board Event Attendee. Frank: Allogene Therapeutics: Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Research Funding. Dahiya: Miltenyi Biotech: Research Funding; Kite, a Gilead Company: Consultancy; Jazz Pharmaceuticals: Research Funding; Atara Biotherapeutics: Consultancy; BMS: Consultancy. McGuirk: Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Gamida Cell: Research Funding; Novartis: Research Funding; Bellicum Pharmaceuticals: Research Funding; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; EcoR1 Capital: Consultancy. Goy: Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Phamacyclics: Research Funding; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Rosewell Park: Consultancy; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Incyte: Honoraria; Hoffman la Roche: Consultancy; LLC(Targeted Oncology): Consultancy; Xcenda: Consultancy, Honoraria; OncLive Peer Exchange: Honoraria; Infinity/Verastem: Research Funding; Genentech/Hoffman la Roche: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medscape: Consultancy; Xcenda: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; MorphoSys: Honoraria, Other; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Hill: Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Gentenech: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria. Oluwole: Pfizer: Consultancy; Curio Science: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Deol: Kite, a Gilead Company: Consultancy. Shah: Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Pfizer: Consultancy, Other: Expenses; Novartis: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; BeiGene: Consultancy, Honoraria; Amgen: Consultancy; Precision Biosciences: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Acrotech/Spectrum: Honoraria; Servier Genetics: Other; Adaptive Biotechnologies: Consultancy. Paludo: Karyopharm: Research Funding. Miklos: Pharmacyclics: Patents & Royalties; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy. Ghobadi: Wugen: Consultancy; Atara: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding. Lin: Legend: Consultancy; Novartis: Consultancy; Gamida Cell: Consultancy; Vineti: Consultancy; Bluebird Bio: Consultancy, Research Funding; Sorrento: Consultancy; Takeda: Research Funding; Merck: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Wang: Moffit Cancer Center: Honoraria; Chinese Medical Association: Honoraria; InnoCare: Consultancy, Research Funding; Epizyme: Consultancy, Honoraria; Hebei Cancer Prevention Federation: Honoraria; Newbridge Pharmaceuticals: Honoraria; Genentech: Consultancy; OMI: Honoraria; Physicians Education Resources (PER): Honoraria; Clinical Care Options: Honoraria; CAHON: Honoraria; VelosBio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; CStone: Consultancy; Loxo Oncology: Consultancy, Research Funding; BioInvent: Research Funding; Juno: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; BGICS: Honoraria; Bayer Healthcare: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Molecular Templates: Research Funding; Imedex: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Dava Oncology: Honoraria; Oncternal: Consultancy, Research Funding; Lilly: Research Funding; Celgene: Research Funding; Anticancer Association: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Scripps: Honoraria; Mumbai Hematology Group: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Jain: BMS, Kite/Gilead, Novartis, Precision Biosciences, Takeda: Consultancy.
Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant
Scordo, Michael , Wang, Trent , Ahn, Kwang Woo , Chen, Yue , Beitinjaneh, Amer , Chen, Andy , Chow, Victor A. , Dholaria, Bhagirathbhai , Epperla, Narendranath , Farooq, Umar , Hamad, Nada , Hildebrandt, Gerhard , Holmberg, Leona , Hong, Sanghee , Inwards, David J. , Jimenez-Jimenez, Antonio Martin, Kenkre, Vaishalee P. , Khimani, Farhad , Klyuchnikov, Evgeny , Krem, Maxwell M. , Munshi, Pashna N. , Prestidge, Tim , Geethakumari, Praveen Ramakrishnan , Rezvani, Andrew R. , Riedell, Peter A. , Seo, Sachiko , Shah, Nirav N. , Solh, Melhem , Kharfan‐Dabaja, Mohamed A. , Herrera, Alex F. , Sauter, Craig S. , Holmberg, Leona , Chen, Andy I. , Dholaria, Bhagirathbhai R , Epperla, Narendranath , Farooq, Umar , Riedell, Peter A , Hamad, Nada , Ahmed, Sairah , Awan, Farrukh T. , Ghosh, Nilanjan , Grover, Natalie S. , Karmali, Reem , Nieto, Yago , Yared, Jean A. , Hamadani, Mehdi
JAMA Oncology | May 7, 2021 | Volume: 7 | Issue: 7 | Pages: 993
Superiority of Thiotepa-Containing Conditioning Regimens in Patients with Primary Diffuse Large B-Cell Lymphoma (DLBCL) of the Central Nervous System (CNS) Undergoing Autologous Hematopoietic Cell Transplantation (autoHCT)
Wang, Trent , Scordo, Michael , Ahn, Kwang Woo , Kharfan‐Dabaja, Mohamed A. , Herrera, Alex F. , Sauter, Craig S. , Chen, Stella , Hamadani, Mehdi
Blood | February 6, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 8-9
INTRODUCTION Primary DLBCL of the CNS (PCNSL) is a rare, extra-nodal non-Hodgkin lymphoma with high risk of relapse without consolidation therapies. AutoHCT has emerged as an accepted consolidation strategy, especially with increasing use of CNS penetrant chemotherapy agents in transplant conditioning. However, studies defining the optimal conditioning regimen for PCNSL have not been performed. The use of two common conditioning regimens in the U.S., thiotepa/busulfan/cyclophosphamide (TBC) and thiotepa/carmustine (TT-BCNU), is supported by phase II trials, but lack comparative data. Extrapolating experience from systemic lymphomas, BEAM (BCNU/etoposide/cytarabine/melphalan) is also prescribed for PCNSL in the U.S. Using the Center for International Blood & Marrow Transplant Research (CIBMTR) registry, we compared outcomes for PCNSL patients undergoing autoHCT using the three most commonly employed conditioning regimens: TBC vs. TT-BCNU vs. BEAM. METHODS Six hundred and eight adult PCNSL patients who underwent a first autoHCT between 2010-2018 were included. Conditioning regimens included TBC (n = 265), TT-BCNU (n = 278), and BEAM (n = 65). The primary endpoint was progression-free survival (PFS). Secondary endpoints included (a) time to hematopoietic recovery, (b) relapse/progression, (c) non-relapse mortality (NRM), and (d) overall survival (OS). Kaplan-Meier method was used to estimate probabilities of PFS and OS. Cox proportional hazard analysis was used to identify prognostic factors for relapse, NRM, PFS, and OS. Variables considered in regression model include patient age, sex, race, performance status, HCT-comorbidity index (HCT-CI), rituximab use during conditioning, interval between diagnosis and HCT, and remission status. Covariates with a p<0.05 were considered significant. RESULTS Baseline characteristics are presented in Table 1. The groups were comparable with regards to median patient age, gender, race, HCT-CI, and remission status. The cumulative incidences of neutrophil recovery at 1-month for the three conditioning regimens were: TBC 96% (95%CI 94-98%), TT-BCNU 100% (95%CI 98-100%), and BEAM 100% (95%CI 100%), (p < 0.001). The cumulative incidence rate of relapse for TBC, TT-BCNU, and BEAM at 1-year were 6% (95%CI 3-9%), 10% (95%CI 7-14%), and 23% (95%CI 14-35%), respectively (p = 0.003). The corresponding cumulative incidence rate of relapse at 3-years were 11% (95%CI 7-16%), 15% (95%CI 10-20%) and 37% (95%CI 25-50%) (p < 0.001) respectively. The adjusted NRM were higher for TBC: 100-day 7% (95%CI 4-10%) and 1-year 11% (95%CI 7-15%), compared to TT-BCNU: 100-day 2% (95%CI 0.2-3%) and 1-year 4% (95%CI 2-6%), and BEAM: 100-day 0% (95%CI 0%) and 1-year 4% (95%CI 0-9%) (1-year p=0.01). The 3-year adjusted PFS across the three conditioning regimens were: TBC 75% (95%CI 69-81%), TT-BCNU 76% (95%CI 70-82%), and BEAM 58% (95%CI 46-70%) (p = 0.03) [Figure 1a]. The adjusted OS at 3-years were: TBC 81% (95%CI 75-86%), TT-BCNU 78% (95%CI 72-85%) and BEAM 69% (95%CI 58-80%), (p = 0.17) [Figure 1b]. Relapse of primary disease was the most common cause of death in all three cohorts: TBC 38% (n=20), TT-BCNU 72% (n=33) and BEAM 76% (n=19). Other significant causes of death in the TBC group included infections 15% (n=8) and organ failure 21% (n=11). CONCLUSIONS In this CIBMTR analysis in patients with PCNSL, we found favorable outcomes with thiotepa-containing conditioning regimens. Adjusted 3-year PFS favored TBC and TT-BCNU over BEAM and suggest that use of BEAM should be discouraged in this specific setting. Whether TBC or TT-BCNU is the optimal conditioning regimen requires further inquiry in a prospective clinical trial. Disclosures Scordo: McKinsey & Company: Consultancy; Omeros Corporation: Consultancy; Kite - A Gilead Company: Other: Ad-hoc advisory board; Angiocrine Bioscience, Inc.: Consultancy, Research Funding. Kharfan-Dabaja:Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy. Herrera:Pharmacyclics: Research Funding; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding. Hamadani:Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; Sanofi Genzyme, AstraZeneca: Speakers Bureau; Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Sauter:Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharamaceuticals: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy, Research Funding; Kite - a Gilead Company: Consultancy; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding; Juno Therapeutics: Consultancy, Research Funding.
Prognostic Impact of a Modified European LeukemiaNet (ELN) Genetic Risk Stratification in Predicting Outcomes for Adults with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT). a Center for International Blood
Wang, Trent , Litzow, Mark R. , Baron, Frédéric , Saad, Ayman , Khera, Nandita , Copelan, Edward A. , DeFilipp, Zachariah , Bredeson, Christopher , Krem, Maxwell M. , Zhang, Mei‐Jie , Chen, Karen , Saber, Wael , Saad, Ayman , Jiménez, Antonio , Lima, Marcos de , Komanduri, Krishna V. , Kebriaei, Partow , Bhatt, Vijaya Raj , Maakaron, Joseph E. , Murthy, Hemant S. , Martino, Rodrigo , Nishihori, Taiga , Weisdorf, Daniel J.
Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 27-29
Background: Allogeneic HCT continues to be the optimal consolidation strategy for many patients with AML. Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes. We tested the prognostic ability of a modified (mELN) classification system based on available CIBMTR genetic data, to predict post-transplant outcomes. Methods: Adult patients with a diagnosis of AML in first complete remission (CR1) with available pre-transplant cytogenetic and molecular mutational data, receiving a first allogeneic HCT from 2013-2017, were included. Patients were stratified according to mELN genetic classification in three distinct groups: favorable (Fav), intermediate (IM) and adverse (Adv). Clinical outcomes following HCT were compared among groups after adjusting for significant patient, disease, and transplant-related variables. The primary endpoint was disease free survival (DFS). Secondary endpoints were overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse, acute GVHD, and chronic GVHD. Cox proportional hazard models were used to compare endpoints among mELN risk groups, age groups and genetic subsets within the adverse-risk group. Results: Demographic characteristics are summarized in Table 1. 2289 patients (Fav, n=181; IM n=1185; and Adv n=923) met the inclusion criteria. Median follow-up for survivors was 35 months. Importantly, 41% of transplant recipients (n=936) were >60 years, 76% (n=1743) had de novo AML and 48% (n=1111) received a myeloablative conditioning regimen. Univariate analysis (UVA) demonstrated significant differences in 2-year OS (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p<0.001); DFS (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p<0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p<0.001) There were no significant differences in NRM (p=0.467) or the incidence of acute (p=0.423) and chronic GVHD (p=0.442) among mELN groups. Initial multivariate analysis (MVA) of mELN risk groups indicated that there was no significant difference in clinical outcomes between the Fav and IM risk groups. Thus, these groups were combined for subsequent analyses. Adv risk (vs. Fav/IM) led to significantly worse OS (HR 1.39 [1.24-1.57] p=<0.001), DFS (HR 1.32 [1.18-1.48] p=<0.001), and relapse (HR 1.42 [1.23-1.63] p=<0.001) (Table 2). This mELN classification effectively stratified both younger (<60 y/o) and older (>60 y/o) patients for OS (Adv vs. Fav/IM HR for <60: 1.43 [1.21-1.69] p<0.001; >60: 1.44 [1.21-1.72] p<0.001), DFS (Adv HR for <60: 1.31 [1.12-1.53] p<0.001; >60: 1.41 [1.19-1.66] p<0.001) and relapse (Adv HR for <60: 1.44 [1.20-1.74] p<0.001, >60: 1.42 [1.15-1.76] p=0.001). NRM was higher for older patients (>60 y/o) in both the Fav/IM (HR 1.40 [1.10-1.78] p=0.007) and Adv-risk cohorts (HR 1.59 [1.18-2.13] p=0.002). Genetic subset comparisons within the adverse-risk group showed that patients carrying monosomy 5, del(5q) or monosomy 7 had inferior 2-year OS (42.6%, p<0.001) and DFS (35.2%, p<0.001), as well as higher rates of relapse (45%, p= 0.002) when compared to other patients within the Adv-risk cohort (OS 60%, DFS 50.8%, relapse 33.5%). Conclusion: Stratification using mELN criteria resulted in clear prognostic separation of OS, DFS and relapse in this large cohort of AML patients undergoing allogeneic HCT. While Fav and IM groups had similar OS, DFS and relapse rates; patients in the Adv risk group had the highest risk of relapse and inferior DFS/OS. However, the majority of patients in all cohorts had favorable outcomes for HCT in CR1. Our findings confirm the value of a combined genetic prognostic model in the AML HCT setting and justify the use of this stratification system in future HCT trials. Correlation of genetic subtypes with other important transplant variables, such as conditioning intensity and pre-transplant MRD status deserves further evaluation. There remains a subset of Adv-risk patients for which post-transplant outcomes continue to be poor, even when transplanted in CR1. Novel peri-transplant pre-emptive/therapeutic strategies are urgently needed for this high-risk cohort. Disclosures de Lima: Celgene: Research Funding; Pfizer: Other: Personal fees, advisory board, Research Funding; BMS: Other: Personal Fees, advisory board; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board. Komanduri:Kiadis: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kebriaei:Ziopharm: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Bhatt:National Marrow Donor Program: Research Funding; Rigel Pharmaceuticals: Other; Jazz: Research Funding; Agios: Other: Personal Fees; Incyte: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees; Partner Therapeutics: Other: Personal Fees; Pfizer: Other, Research Funding; CSL Behring: Other; Tolero Pharmaceuticals: Research Funding; Oncoceutics: Other: Drug support for a trial; Partnership for health analytic research, LLC: Other: Personal Fees; Omeros: Other: Personal Fees; Abbvie: Other: Personal Fees, Research Funding. Saad:Orcabio: Other: research support; Kadmon: Other: research support; Amgen: Other: research support; Incyte Pharmaceuticals: Other: Personal Fees; Magenta Therapeutics: Other: Personal Fees. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Defilipp:Incyte: Research Funding; Regimmune: Research Funding; Syndax Pharmaceuticals: Consultancy. Nishihori:Karyopharm: Other: Research support to institution; Novartis: Other: Research support to institution. Weisdorf:Incyte: Research Funding; FATE Therapeutics: Consultancy.