المؤلفون: Wang, Yucai, Jain, Preetesh, Locke, Frederick, Maurer, Matthew, Frank, Matthew, Munoz, Javier, Dahiya, Saurabh, Beitinjaneh, Amer, Jacobs, Miriam, Mcguirk, Joseph, Vose, Julie, Goy, Andre, Hill, Brian, Dorritie, Kathleen, Oluwole, Olalekan, Deol, Abhinav, Paludo, Jonas, Shah, Bijal, Wang, Trent, Banerjee, Rahul, Miklos, David, Rapoport, Aaron, Lekakis, Lazaros, Ghobadi, Armin, Neelapu, Sattva, Lin, Yi, Wang, Michael, Jain, Michael, Andreadis, Charalambos

المصدر: Journal of Clinical Oncology. 41(14)

مصطلحات موضوعية: Adult, Humans, Receptors, Chimeric Antigen, Lymphoma, Mantle-Cell, Bendamustine Hydrochloride, Neoplasm Recurrence, Local, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Antigens, CD19

الوصف: 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.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/53p514tc

المؤلفون: Rezvan, Ali, Romain, Gabrielle, Fathi, Mohsen, Heeke, Darren, Martinez-Paniagua, Melisa, An, Xingyue, Bandey, Irfan N., Montalvo, Melisa J., Adolacion, Jay R. T., Saeedi, Arash, Sadeghi, Fatemeh, Fousek, Kristen, Puebla-Osorio, Nahum, Cooper, Laurence J. N., Bernatchez, Chantale, Singh, Harjeet, Ahmed, Nabil, Mattie, Mike, Bot, Adrian, Neelapu, Sattva, Varadarajan, Navin^{Aff1, IDs43018024007861_cor21}

المصدر: Nature Cancer. 5(6):954-954

المؤلفون: Steiner, Raphael E.^{Aff1, IDs40164023003960_cor1}, Parra, Edwin R., Vega, Francisco, Feng, Lei, Westin, Jason R., Neelapu, Sattva S., Strati, Paolo, Green, Michael R., Flowers, Christopher R., Solis, Luisa M., Wistuba, Ignacio I., Ahmed, Sairah, Nair, Ranjit, Hagemeister, Fredrick B., Noorani, Mansoor, Marques-Piubelli, Mario L.

المصدر: Experimental Hematology & Oncology. 12(1)

المؤلفون: Gunther, Jillian R ^*, Xu, Jie, Bhutani, Manoop S, Strati, Paolo, Fang, Penny Q, Wu, Susan Y, Dabaja, Bouthaina S, Dong, Wenli, Bhosale, Priya R, Flowers, Christopher R, Nair, Ranjit, Malpica Castillo, Luis, Fayad, Luis, Iyer, Swaminathan P, Parmer, Simrit, Wang, Michael, Lee, Hun Ju, Samaniego, Felipe, Westin, Jason, Ahmed, Sairah, Nze, Chijioke C, Jain, Preetesh, Neelapu, Sattva S, Rodriguez, Maria A, Chihara, Dai, Nastoupil, Loretta J, Pinnix, Chelsea C

المصدر: In The Lancet Haematology July 2024 11(7):e521-e529

المؤلفون: Cai, Tianyu, Gouble, Agnès, Black, Kathryn, Skwarska, Anna, Naqvi, Ammar, Taylor, Deanne, Zhao, Ming, Yuan, Qi, Sugita, Mayumi, Zhang, Qi, Galetto, Roman, Filipe, Stéphanie, Cavazos, Antonio, Han, Lina, Kuruvilla, Vinitha, Ma, Helen, Weng, Connie, Liu, Chang-Gong, Liu, Xiuping, Konoplev, Sergej, Gu, Jun, Tang, Guilin, Su, Xiaoping, Al-Atrash, Gheath, Neelapu, Sattva, Lane, Andrew, Kantarjian, Hagop, Guzman, Monica, Pemmaraju, Naveen, Smith, Julianne, Thomas-Tikhonenko, Andrei, Konopleva, Marina, Ciurea, Stefan

المصدر: Nature Communications. 13(1)

مصطلحات موضوعية: Acute Disease, Animals, Dendritic Cells, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Interleukin-3 Receptor alpha Subunit, Mice, Myeloproliferative Disorders, Skin Neoplasms

الوصف: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN® nucleases. In this study, we examine the antitumor activity of UCART123 in preclinical models of BPDCN. We report that UCART123 have selective antitumor activity against CD123-positive primary BPDCN samples (while sparing normal hematopoietic progenitor cells) in the in vitro cytotoxicity and T cell degranulation assays; supported by the increased secretion of IFNγ by UCART123 cells when cultured in the presence of BPDCN cells. UCART123 eradicate BPDCN and result in long-term disease-free survival in a subset of primary patient-derived BPDCN xenograft mouse models. One potential challenge of CD123 targeting therapies is the loss of CD123 antigen through diverse genetic mechanisms, an event observed in one of three BPDCN PDX studied. In summary, these results provide a preclinical proof-of-principle that allogeneic UCART123 cells have potent anti-BPDCN activity.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/96n41927

المؤلفون: Jain, Michael D., Jacobs, Miriam T., Gao, Feng, Nastoupil, Loretta J., Spiegel, Jay Y., Lin, Yi, Dahiya, Saurabh, Lunning, Matthew, Lekakis, Lazaros, Reagan, Patrick, Oluwole, Olalekan, McGuirk, Joseph, Deol, Abhinav, Sehgal, Alison R., Goy, Andre, Hill, Brian T., Andreadis, Charalambos, Munoz, Javier, Chavez, Julio C, Bennani, N. Nora, Rapoport, Aaron P., Vose, Julie M., Miklos, David, Neelapu, Sattva S., Locke, Frederick L., Ghobadi, Armin

المصدر: In Blood Advances 27 February 2024 8(4):1042-1050

المؤلفون: Neelapu, Sattva S., Chavez, Julio C., Sehgal, Alison R., Epperla, Narendranath, Ulrickson, Matthew, Bachy, Emmanuel, Munshi, Pashna N., Casulo, Carla, Maloney, David G., de Vos, Sven, Reshef, Ran, Leslie, Lori A., Oluwole, Olalekan O., Yakoub-Agha, Ibrahim, Khanal, Rashmi, Rosenblatt, Joseph, Korn, Ronald, Peng, Weixin, Lui, Christine, Wulff, Jacob, Shen, Rhine, Poddar, Soumya, Jung, A. Scott, Miao, Harry, Beygi, Sara, Jacobson, Caron A.

المصدر: In Blood 8 February 2024 143(6):496-506

المؤلفون: Stein-Thoeringer, Christoph K.^{Aff1, Aff14}, Saini, Neeraj Y.^{Aff2, Aff3, IDs41591023022346_cor2}, Zamir, Eli, Blumenberg, Viktoria^{Aff4, Aff5, Aff6}, Schubert, Maria-Luisa, Mor, Uria, Fante, Matthias A., Schmidt, Sabine, Hayase, Eiko, Hayase, Tomo, Rohrbach, Roman, Chang, Chia-Chi, McDaniel, Lauren, Flores, Ivonne, Gaiser, Rogier, Edinger, Matthias^{Aff6, Aff9, Aff11}, Wolff, Daniel^{Aff6, Aff9, Aff11}, Heidenreich, Martin^{Aff6, Aff11}, Strati, Paolo, Nair, Ranjit, Chihara, Dai, Fayad, Luis E., Ahmed, Sairah, Iyer, Swaminathan P., Steiner, Raphael E., Jain, Preetesh, Nastoupil, Loretta J., Westin, Jason, Arora, Reetakshi, Wang, Michael L., Turner, Joel, Menges, Meghan, Hidalgo-Vargas, Melanie, Reid, Kayla, Dreger, Peter, Schmitt, Anita, Müller-Tidow, Carsten, Locke, Frederick L., Davila, Marco L., Champlin, Richard E., Flowers, Christopher R., Shpall, Elizabeth J., Poeck, Hendrik^{Aff6, Aff9, Aff11}, Neelapu, Sattva S., Schmitt, Michael, Subklewe, Marion^{Aff4, Aff5, Aff6}, Jain, Michael D.^{Aff13, IDs41591023022346_cor47}, Jenq, Robert R.^{Aff2, Aff10, Aff15, IDs41591023022346_cor48}, Elinav, Eran^{Aff1, Aff8, IDs41591023022346_cor49}

المصدر: Nature Medicine. 29(4):906-916

المؤلفون: Strati, Paolo^{Aff1, Aff2, IDs4137502201704z_cor1}, Jallouk, Andrew P., Sun, Ryan, Choi, Jaihee, Das, Kaberi, Cherng, Hua-Jay, Ahmed, Sairah, Lee, Hun J., Iyer, Swaminathan P., Nair, Ranjit, Nastoupil, Loretta J., Steiner, Raphael E., Huff, Chad D., Yu, Yao, Mistry, Haleigh, Pulsifer, Brittany, Noorani, Mansoor, Saini, Neeraj, Shpall, Elizabeth J., Kebriaei, Partow, Flowers, Christopher R., Westin, Jason R., Hildebrandt, Michelle A. T., Neelapu, Sattva S.

المصدر: Leukemia. 36(11):2669-2677

المؤلفون: Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan^{Aff4, Aff5}, Rodriguez, Emma, Hussain, Zulekha, Neelapu, Sattva S., Wang, Jennifer, Shah, Amishi Y., Tannir, Nizar M., Campbell, Matthew T., Gibbons, Don L., Cascone, Tina, Lu, Charles, Blumenschein, George R., Altan, Mehmet, Lim, Bora, Valero, Vincente, Loghin, Monica E., Tu, Janet, Westin, Shannon N., Naing, Aung, Garcia-Manero, Guillermo, Abdel-Wahab, Noha^{Aff1, Aff16, Aff17}, Tawbi, Hussein A., Hwu, Patrick^{Aff16, Aff20}, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua^{Aff2, Aff19, IDs41467024497339_cor37}, Nurieva, Roza^{Aff4, Aff19, IDs41467024497339_cor38}

المصدر: Nature Communications. 15(1)