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320 results on '"Diab, Adi"'

1. Author Correction: Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, 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, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2024
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2. Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

Author

El Zarif, Talal, Nassar, Amin, Adib, Elio, Fitzgerald, Bailey, Huang, Jiaming, Mouhieddine, Tarek, Rubinstein, Paul, Nonato, Taylor, McKay, Rana, Li, Mingjia, Mittra, Arjun, Owen, Dwight, Baiocchi, Robert, Lorentsen, Michael, Dittus, Christopher, Dizman, Nazli, Falohun, Adewunmi, Abdel-Wahab, Noha, Diab, Adi, Bankapur, Anand, Reed, Alexandra, Kim, Chul, Arora, Aakriti, Shah, Neil, El-Am, Edward, Kozaily, Elie, Abdallah, Wassim, Al-Hader, Ahmad, Abu Ghazal, Batool, Saeed, Anwaar, Drolen, Claire, Lechner, Melissa, Drakaki, Alexandra, Baena, Javier, Nebhan, Caroline, Haykal, Tarek, Morse, Michael, Cortellini, Alessio, Pinato, David, Dalla Pria, Alessia, Hall, Evan, Bakalov, Veli, Bahary, Nathan, Rajkumar, Aarthi, Mangla, Ankit, Shah, Vishal, Singh, Parminder, Aboubakar Nana, Frank, Lopetegui-Lia, Nerea, Dima, Danai, Dobbs, Ryan, Funchain, Pauline, Saleem, Rabia, Woodford, Rachel, Long, Georgina, Menzies, Alexander, Genova, Carlo, Barletta, Giulia, Puri, Sonam, Florou, Vaia, Idossa, Dame, Saponara, Maristella, Queirolo, Paola, Lamberti, Giuseppe, Addeo, Alfredo, Bersanelli, Melissa, Freeman, Dory, Xie, Wanling, Reid, Erin, Chiao, Elizabeth, Sharon, Elad, Johnson, Douglas, Ramaswami, Ramya, Bower, Mark, Emu, Brinda, Marron, Thomas, Choueiri, Toni, Baden, Lindsey, Lurain, Kathryn, Sonpavde, Guru, and Naqash, Abdul

Subjects
Male, Humans, Middle Aged, Female, Carcinoma, Hepatocellular, Immune Checkpoint Inhibitors, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Liver Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Head and Neck Neoplasms, HIV Infections
Abstract

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load

Published
2023

3. Tilsotolimod Exploits the TLR9 Pathway to Promote Antigen Presentation and Type 1 IFN Signaling in Solid Tumors: A Multicenter International Phase I/II Trial (ILLUMINATE-101).

Author

Babiker, Hani, Borazanci, Erkut, Subbiah, Vivek, Agarwala, Sanjiv, Algazi, Alain, Schachter, Jacob, Lotem, Michael, Maurice-Dror, Corinne, Hendler, Daniel, Rahimian, Shah, Minderman, Hans, Haymaker, Cara, Mahadevan, Daruka, Bernatchez, Chantale, Murthy, Ravi, Hultsch, Rolf, Kaplan, Nadia, Woodhead, Gregory, Hennemeyer, Charles, Chunduru, Srinivas, Anderson, Peter, Diab, Adi, and Puzanov, Igor

Subjects
Humans, Toll-Like Receptor 9, Antigen Presentation, Neoplasms, Melanoma, Cohort Studies, Skin Neoplasms, Tumor Microenvironment
Abstract

PURPOSE: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors. PATIENTS AND METHODS: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the safety, establishing the dose, efficacy, and immunologic assessment. Blood samples and tumor biopsies of injected and noninjected lesions were obtained at baseline and 24 hours after treatment for immune analyses. RESULTS: Thirty-eight and 16 patients were enrolled into the dose escalation and melanoma expansion cohorts, respectively. Deep visceral injections were conducted in 91% of patients. No dose-limiting toxicities (DLT) or grade 4 treatment-related adverse events were observed. Biopsies 24 hours after treatment demonstrated an increased IFN pathway signature and dendritic cell maturation. Immunologic profiling revealed upregulation of IFN-signaling genes and modulation of genes for checkpoint proteins. In the dose escalation cohort, 12 (34%) of 35 evaluable patients achieved a best overall response rate (ORR) of stable disease (SD), whereas 3 (19%) of 16 evaluable patients in the melanoma cohort achieved stable disease. CONCLUSIONS: Overall, tilsotolimod monotherapy was generally well tolerated and induced rapid, robust alterations in the tumor microenvironment. See related commentary by Punekar and Weber, p. 5007.

Published
2022

5. Author Correction: Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results

Author

Glitza Oliva, Isabella C., Ferguson, Sherise D., Bassett, Jr, Roland, Foster, Alexandra P., John, Ida, Hennegan, Tarin D., Rohlfs, Michelle, Richard, Jessie, Iqbal, Masood, Dett, Tina, Lacey, Carol, Jackson, Natalie, Rodgers, Theresa, Phillips, Suzanne, Duncan, Sheila, Haydu, Lauren, Lin, Ruitao, Amaria, Rodabe N., Wong, Michael K., Diab, Adi, Yee, Cassian, Patel, Sapna P., McQuade, Jennifer L., Fischer, Grant M., McCutcheon, Ian E., O’Brien, Barbara J., Tummala, Sudhakar, Debnam, Matthew, Guha-Thakurta, Nandita, Wargo, Jennifer A., Carapeto, Fernando C. L., Hudgens, Courtney W., Huse, Jason T., Tetzlaff, Michael T., Burton, Elizabeth M., Tawbi, Hussein A., and Davies, Michael A.

Published
2024
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6. Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results

Author

Glitza Oliva, Isabella C., Ferguson, Sherise D., Bassett, Jr, Roland, Foster, Alexandra P., John, Ida, Hennegan, Tarin D., Rohlfs, Michelle, Richard, Jessie, Iqbal, Masood, Dett, Tina, Lacey, Carol, Jackson, Natalie, Rodgers, Theresa, Phillips, Suzanne, Duncan, Sheila, Haydu, Lauren, Lin, Ruitao, Amaria, Rodabe N., Wong, Michael K., Diab, Adi, Yee, Cassian, Patel, Sapna P., McQuade, Jennifer L., Fischer, Grant M., McCutcheon, Ian E., O’Brien, Barbara J., Tummala, Sudhakar, Debnam, Matthew, Guha-Thakurta, Nandita, Wargo, Jennifer A., Carapeto, Fernando C. L., Hudgens, Courtney W., Huse, Jason T., Tetzlaff, Michael T., Burton, Elizabeth M., Tawbi, Hussein A., and Davies, Michael A.

Published
2023
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7. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant

Author

Murakami, Naoka, Mulvaney, Patrick, Danesh, Melissa, Abudayyeh, Ala, Diab, Adi, Abdel-Wahab, Noha, Abdelrahim, Maen, Khairallah, Pascale, Shirazian, Shayan, Kukla, Aleksandra, Owoyemi, Itunu O, Alhamad, Tarek, Husami, Samir, Menon, Madhav, Santeusanio, Andrew, Blosser, Christopher D, Zuniga, Sandra Carias, Soler, Maria Jose, Moreso, Francesc, Mithani, Zain, Ortiz-Melo, David, Jaimes, Edgar A, Gutgarts, Victoria, Lum, Erik, Danovitch, Gabriel M, Cardarelli, Francesca, Drews, Reed E, Bassil, Claude, Swank, Jennifer L, Westphal, Scott, Mannon, Roslyn B, Shirai, Keisuke, Kitchlu, Abhijat, Ong, Song, Machado, Shana M, Mothi, Suraj S, Ott, Patrick A, Rahma, Osama, Hodi, F Stephen, Sise, Meghan E, Gupta, Shruti, Leaf, David E, Devoe, Craig E, Wanchoo, Rimda, Nair, Vinay V, Schmults, Chrysalyne D, Hanna, Glenn J, Sprangers, Ben, Riella, Leonardo V, Jhaveri, Kenar D, and Consortium, Immune Checkpoint Inhibitors in Solid Organ Transplant

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Organ Transplantation, Kidney Disease, Transplantation, Cancer, Rare Diseases, Clinical Research, Prevention, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Renal and urogenital, Carcinoma, Squamous Cell, Humans, Immune Checkpoint Inhibitors, Kidney Transplantation, Prospective Studies, Retrospective Studies, Skin Neoplasms, immune checkpoint inhibitors, kidney transplant, onconephrology, rejection, Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium, Urology & Nephrology, Clinical sciences
Abstract

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Published
2021

8. Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma

Author

Grasso, Catherine S, Tsoi, Jennifer, Onyshchenko, Mykola, Abril-Rodriguez, Gabriel, Ross-Macdonald, Petra, Wind-Rotolo, Megan, Champhekar, Ameya, Medina, Egmidio, Torrejon, Davis Y, Shin, Daniel Sanghoon, Tran, Phuong, Kim, Yeon Joo, Puig-Saus, Cristina, Campbell, Katie, Vega-Crespo, Agustin, Quist, Michael, Martignier, Christophe, Luke, Jason J, Wolchok, Jedd D, Johnson, Douglas B, Chmielowski, Bartosz, Hodi, F Stephen, Bhatia, Shailender, Sharfman, William, Urba, Walter J, Slingluff, Craig L, Diab, Adi, Haanen, John BAG, Algarra, Salvador Martin, Pardoll, Drew M, Anagnostou, Valsamo, Topalian, Suzanne L, Velculescu, Victor E, Speiser, Daniel E, Kalbasi, Anusha, and Ribas, Antoni

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Good Health and Well Being, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Published
2021

10. Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma

Author

Grasso, Catherine S, Tsoi, Jennifer, Onyshchenko, Mykola, Abril-Rodriguez, Gabriel, Ross-Macdonald, Petra, Wind-Rotolo, Megan, Champhekar, Ameya, Medina, Egmidio, Torrejon, Davis Y, Shin, Daniel Sanghoon, Tran, Phuong, Kim, Yeon Joo, Puig-Saus, Cristina, Campbell, Katie, Vega-Crespo, Agustin, Quist, Michael, Martignier, Christophe, Luke, Jason J, Wolchok, Jedd D, Johnson, Douglas B, Chmielowski, Bartosz, Hodi, F Stephen, Bhatia, Shailender, Sharfman, William, Urba, Walter J, Slingluff, Craig L, Diab, Adi, Haanen, John BAG, Algarra, Salvador Martin, Pardoll, Drew M, Anagnostou, Valsamo, Topalian, Suzanne L, Velculescu, Victor E, Speiser, Daniel E, Kalbasi, Anusha, and Ribas, Antoni

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Genetics, Vaccine Related, Human Genome, Immunization, Cancer, Aetiology, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cell Line, Cell Line, Tumor, Female, Gene Expression Profiling, Humans, Immune Checkpoint Inhibitors, Interferon-gamma, Ipilimumab, Male, Melanoma, Middle Aged, Nivolumab, T-Lymphocytes, Transcriptome, Young Adult, RNA-seq, anti-CTLA-4, anti-PD-1, biopsies, clinical trial, immune checkpoint blockade, immune exclusion, interferon-γ, resistance, response, transcriptomics, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations. This conserved IFN-γ transcriptome response in melanoma cells serves to amplify the antitumor immune response. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFN-γ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

Published
2020

11. Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist.

Author

Parisi, Giulia, Saco, Justin D, Salazar, Felix B, Tsoi, Jennifer, Krystofinski, Paige, Puig-Saus, Cristina, Zhang, Ruixue, Zhou, Jing, Cheung-Lau, Gardenia C, Garcia, Alejandro J, Grasso, Catherine S, Tavaré, Richard, Hu-Lieskovan, Siwen, Mackay, Sean, Zalevsky, Jonathan, Bernatchez, Chantale, Diab, Adi, Wu, Anna M, Comin-Anduix, Begoña, Charych, Deborah, and Ribas, Antoni

Subjects
T-Lymphocytes, Animals, Mice, Inbred C57BL, Humans, Mice, Melanoma, Melanoma, Experimental, Polyethylene Glycols, Receptors, Interleukin-2, Interleukin-2, Adoptive Transfer, Lymphocyte Activation, Inbred C57BL, Experimental, Receptors
Abstract

Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.

Published
2020

12. Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Amaria, Rodabe N., Postow, Michael, Burton, Elizabeth M., Tezlaff, Michael T., Ross, Merrick I., Torres-Cabala, Carlos, Glitza, Isabella C., Duan, Fei, Milton, Denái R., Busam, Klaus, Simpson, Lauren, McQuade, Jennifer L., Wong, Michael K., Gershenwald, Jeffrey E., Lee, Jeffrey E., Goepfert, Ryan P., Keung, Emily Z., Fisher, Sarah B., Betof-Warner, Allison, Shoushtari, Alexander N., Callahan, Margaret, Coit, Daniel, Bartlett, Edmund K., Bello, Danielle, Momtaz, Parisa, Nicholas, Courtney, Gu, Aidi, Zhang, Xuejun, Korivi, Brinda Rao, Patnana, Madhavi, Patel, Sapna P., Diab, Adi, Lucci, Anthony, Prieto, Victor G., Davies, Michael A., Allison, James P., Sharma, Padmanee, Wargo, Jennifer A., Ariyan, Charlotte, and Tawbi, Hussein A.

Published
2022
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13. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial

Author

Naing, Aung, Wong, Deborah J, Infante, Jeffrey R, Korn, W Michael, Aljumaily, Raid, Papadopoulos, Kyriakos P, Autio, Karen A, Pant, Shubham, Bauer, Todd M, Drakaki, Alexandra, Daver, Naval G, Hung, Annie, Ratti, Navneet, McCauley, Scott, Van Vlasselaer, Peter, Verma, Rakesh, Ferry, David, Oft, Martin, Diab, Adi, Garon, Edward B, and Tannir, Nizar M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Lung, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Interleukin-10, Male, Middle Aged, Neoplasms, Nivolumab, Polyethylene Glycols, Programmed Cell Death 1 Receptor, United States, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundIL-10 has anti-inflammatory and CD8+ T-cell stimulating activities. Pegilodecakin (pegylated IL-10) is a first-in-class, long-acting IL-10 receptor agonist that induces oligoclonal T-cell expansion and has single-agent activity in advanced solid tumours. We assessed the safety and activity of pegilodecakin with anti-PD-1 monoclonal antibody inhibitors in patients with advanced solid tumours.MethodsWe did a multicentre, multicohort, open-label, phase 1b trial (IVY) at 12 cancer research centres in the USA. Patients were assigned sequentially into cohorts. Here, we report on all enrolled patients from two cohorts treated with pegilodecakin combined with anti-PD-1 inhibitors. Eligible patients were aged at least 18 years with histologically or cytologically confirmed advanced malignant solid tumours refractory to previous therapies, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with uncontrolled infectious diseases were excluded. Pegilodecakin was provided in single-use 3 mL vials and was self-administered subcutaneously by injection at home at 10 μg/kg or 20 μg/kg once per day in combination with pembrolizumab (2 mg/kg every 3 weeks or 200 mg every 3 weeks) or nivolumab (3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks at the approved dosing), both of which were given intravenously at the study site. Patients received pembrolizumab or nivolumab with pegilodecakin until disease progression, toxicity necessitating treatment discontinuation, patient withdrawal of consent, or study end. The primary endpoints were safety and tolerability, assessed in all patients enrolled in the study who received any amount of study medication including at least one dose of pegilodecakin, and pharmacokinetics (previously published). Secondary endpoints included objective response by immune-related response criteria in all patients who were treated and had evaluable measurements. The study is active but no longer recruiting, and is registered with ClinicalTrials.gov, NCT02009449.FindingsBetween Feb 13, 2015, and Sept 12, 2017, 111 patients were enrolled in the two cohorts. 53 received pegilodecakin plus pembrolizumab, and 58 received pegilodecakin plus nivolumab. 34 (31%) of 111 patients had non-small-cell lung cancer, 37 (33%) had melanoma, and 38 (34%) had renal cell carcinoma; one (

Published
2019

15. Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity

Author

Hailemichael, Yared, Johnson, Daniel H., Abdel-Wahab, Noha, Foo, Wai Chin, Bentebibel, Salah-Eddine, Daher, May, Haymaker, Cara, Wani, Khalida, Saberian, Chantal, Ogata, Dai, Kim, Sang T., Nurieva, Roza, Lazar, Alexander J., Abu-Sbeih, Hamzah, Fa'ak, Faisal, Mathew, Antony, Wang, Yinghong, Falohun, Adewunmi, Trinh, Van, Zobniw, Chrystia, Spillson, Christine, Burks, Jared K., Awiwi, Muhammad, Elsayes, Khaled, Soto, Luisa Solis, Melendez, Brenda D., Davies, Michael A., Wargo, Jennifer, Curry, Jonathan, Yee, Cassian, Lizee, Gregory, Singh, Shalini, Sharma, Padmanee, Allison, James P., Hwu, Patrick, Ekmekcioglu, Suhendan, and Diab, Adi

Published
2022
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17. Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, 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, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2022
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19. High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial

Author

Patel, Roshal R., He, Kewen, Barsoumian, Hampartsoum B., Chang, Joe Y., Tang, Chad, Verma, Vivek, Comeaux, Nathan, Chun, Stephen G., Gandhi, Saumil, Truong, Mylene T., Erasmus, Jeremy J., Hong, David S., Lee, Percy P., Ning, Matthew S., Nguyen, Quynh-Nhu, Heymach, John V., Altan, Mehmet, Blumenschein, George, Fossella, Frank V., Sezen, Duygu, Chen, Dawei, Carter, Brett W., Davies, Michael A., Glitza, Isabella C., Diab, Adi, Ferrarotto, Renata, Cabanillas, Maria E., Yuan, Ying, Shah, Shalin J., Parra, Edwin R., Sun, Baohua, Cortez, Maria Angelica, and Welsh, James W.

Published
2021
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20. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Andrews, Miles C., Duong, Connie P. M., Gopalakrishnan, Vancheswaran, Iebba, Valerio, Chen, Wei-Shen, Derosa, Lisa, Khan, Md Abdul Wadud, Cogdill, Alexandria P., White, Michael G., Wong, Matthew C., Ferrere, Gladys, Fluckiger, Aurélie, Roberti, Maria P., Opolon, Paule, Alou, Maryam Tidjani, Yonekura, Satoru, Roh, Whijae, Spencer, Christine N., Curbelo, Irina Fernandez, Vence, Luis, Reuben, Alexandre, Johnson, Sarah, Arora, Reetakshi, Morad, Golnaz, Lastrapes, Matthew, Baruch, Erez N., Little, Latasha, Gumbs, Curtis, Cooper, Zachary A., Prieto, Peter A., Wani, Khalida, Lazar, Alexander J., Tetzlaff, Michael T., Hudgens, Courtney W., Callahan, Margaret K., Adamow, Matthew, Postow, Michael A., Ariyan, Charlotte E., Gaudreau, Pierre-Olivier, Nezi, Luigi, Raoult, Didier, Mihalcioiu, Catalin, Elkrief, Arielle, Pezo, Rossanna C., Haydu, Lauren E., Simon, Julie M., Tawbi, Hussein A., McQuade, Jennifer, Hwu, Patrick, Hwu, Wen-Jen, Amaria, Rodabe N., Burton, Elizabeth M., Woodman, Scott E., Watowich, Stephanie, Diab, Adi, Patel, Sapna P., Glitza, Isabella C., Wong, Michael K., Zhao, Li, Zhang, Jianhua, Ajami, Nadim J., Petrosino, Joseph, Jenq, Robert R., Davies, Michael A., Gershenwald, Jeffrey E., Futreal, P. Andrew, Sharma, Padmanee, Allison, James P., Routy, Bertrand, Zitvogel, Laurence, and Wargo, Jennifer A.

Published
2021
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22. Survival and treatment outcomes in patients with leptomeningeal disease from metastatic melanoma.

Author

Saberian, Chantal, Milton, Denái R, Simon, Julie, Amaria, Rodabe N, Diab, Adi, McQuade, Jennifer, Patel, Sapna P, Tawbi, Hussein, Yee, Cassian, Wong, Michael K, McCutcheon, Ian E, Davies, Michael A, Ferguson, Sherise D, and Oliva, Isabella C Glitza

Subjects
MENINGEAL cancer, SURVIVAL rate, PROPORTIONAL hazards models, TREATMENT effectiveness, SPINAL infusions, MAGNETIC resonance imaging
Abstract

Background Melanoma leptomeningeal disease (LMD) has a poor prognosis. However, the management of patients with advanced melanoma has evolved with time, including those with LMD. We reviewed a large cohort of melanoma LMD patients to assess factors associated with survival. Methods Retrospective clinical data was collected on patients diagnosed with LMD at MD Anderson Cancer Center from 2015 to 2020. Overall survival (OS) was determined from LMD diagnosis to date of death or last follow-up. The Kaplan–Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable associations of survival with variables of interest were determined using Cox proportional hazards regression models. Results A total of 172 patients were identified. The median age at LMD diagnosis was 53 (range 20–79) years, and all patients had radiographic evidence of LMD on magnetic resonance imaging of either brain or spine. In total 143 patients previously received systemic therapy (83%), with a median of 2 prior treatments (range 0–5). 81 patients (47%) had concurrent uncontrolled systemic disease and 80 patients (53%) had elevated serum LDH at the time of diagnosis. With a median follow-up of 4.0 months (range 0.1–65.3 months), median OS for all patients from LMD diagnosis was 4.9 months. Patients (n  = 45) who received intrathecal therapy or systemic immunotherapy for LMD had a median OS of 8.0 months and 10.2 months, respectively. On multivariable analysis, decreased performance status, positive CSF cytology, elevated LDH, and whole brain radiation were associated with worse OS. Conclusions Despite many advances in therapeutic options, the outcomes of melanoma patients with LMD remains poor. However, a subset of patients appears to derive benefit from LMD-directed treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

Author

Gogas, Helen, Ravimohan, Shruthi, Datta, Antara, Chhibber, Aparna, Couselo, Eva Muñoz, Diab, Adi, Pereira, Caio, Quéreux, Gaëlle, Sandhu, Shahneen, Curti, Brendan, Khushalani, Nikhil I., Taylor, Matthew H., Daniels, Gregory A., Spreafico, Anna, Meniawy, Tarek, Van Den Eertwegh, Alfons J. M., Sun, Yongliang, Arriaga, Yull, Zhou, Ming, and Long, Georgina V.

Subjects
REGULATORY T cells, TUMOR markers, NIVOLUMAB, BIOMARKERS, T cells
Abstract

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Author Correction: Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Amaria, Rodabe N., Postow, Michael, Burton, Elizabeth M., Tetzlaff, Michael T., Ross, Merrick I., Torres-Cabala, Carlos, Glitza, Isabella C., Duan, Fei, Milton, Denái R., Busam, Klaus, Simpson, Lauren, McQuade, Jennifer L., Wong, Michael K., Gershenwald, Jeffrey E., Lee, Jeffrey E., Goepfert, Ryan P., Keung, Emily Z., Fisher, Sarah B., Betof-Warner, Allison, Shoushtari, Alexander N., Callahan, Margaret, Coit, Daniel, Bartlett, Edmund K., Bello, Danielle, Momtaz, Parisa, Nicholas, Courtney, Gu, Aidi, Zhang, Xuejun, Korivi, Brinda Rao, Patnana, Madhavi, Patel, Sapna P., Diab, Adi, Lucci, Anthony, Prieto, Victor G., Davies, Michael A., Allison, James P., Sharma, Padmanee, Wargo, Jennifer A., Ariyan, Charlotte, and Tawbi, Hussein A.

Published
2023
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27. A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling.

Author

McArthur, Heather, Diab, Adi, Page, David, Yuan, Jianda, Solomon, Stephen, Sacchini, Virgilio, Comstock, Christopher, Durack, Jeremy, Maybody, Majid, Sung, Janice, Ginsberg, Arielle, Wong, Phillip, Barlas, Afsar, Dong, Zhiwan, Zhao, Chunjun, Blum, Brian, Patil, Sujata, Neville, Deirdre, Comen, Elizabeth, Kotin, Alan, Brogi, Edi, Wen, Y, Morrow, Monica, Lacouture, Mario, Sharma, Padmanee, Allison, James, Hudis, Clifford, Wolchok, Jedd, Norton, Larry, and Morris, Elizabeth

Subjects
Adult, Aged, Antigens, Neoplasm, Antineoplastic Agents, Immunological, Breast Neoplasms, Combined Modality Therapy, Cryosurgery, Female, Humans, Ipilimumab, Middle Aged, Pilot Projects, Preoperative Care, Receptor, ErbB-2, T-Lymphocytes, Regulatory
Abstract

PURPOSE: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. EXPERIMENTAL DESIGN: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activation were performed on peripheral blood and tumor. RESULTS: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. CONCLUSIONS: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy. Clin Cancer Res; 22(23); 5729-37. ©2016 AACR.

Published
2016

28. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A, Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A, Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K, Wolchok, Jedd D, Merghoub, Taha, Lum, Lawrence G, Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P, Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A, Hwu, Patrick, Overwijk, Willem W, Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H, Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C, Urba, Walter, Schadendorf, Dirk, Ferris, Robert L, Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J, Sharfman, William, Barlesi, Fabrice, Ott, Patrick A, Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, and Qiao, Guanxi

Subjects
Good Health and Well Being
Published
2016

29. Deep Sequencing of T-cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy.

Author

Page, David, Yuan, Jianda, Redmond, David, Wen, Y, Durack, Jeremy, Emerson, Ryan, Solomon, Stephen, Dong, Zhiwan, Wong, Phillip, Comstock, Christopher, Diab, Adi, Sung, Janice, Maybody, Majid, Brogi, Edi, Morrow, Monica, Sacchini, Virgilio, Elemento, Olivier, Robins, Harlan, Patil, Sujata, Allison, James, Wolchok, Jedd, Hudis, Clifford, Norton, Larry, McArthur, Heather, and Morris, Elizabeth

Subjects
Antineoplastic Agents, Immunological, Biomarkers, Tumor, Biopsy, Breast Neoplasms, Combined Modality Therapy, Cryosurgery, DNA, Neoplasm, Feasibility Studies, Female, High-Throughput Nucleotide Sequencing, Humans, Immunotherapy, Ipilimumab, Leukemic Infiltration, Lymphocyte Count, Lymphocytes, Tumor-Infiltrating, Mastectomy, Neoplasm Staging, Pilot Projects, Receptors, Antigen, T-Cell, alpha-beta, Sequence Analysis, DNA
Abstract

In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti-CTLA-4 (ipilimumab), or cryoablation + ipilimumab. TCRs within serially collected peripheral blood and tumor tissue were sequenced. In baseline tumor tissues, T-cell density as measured by TCR sequencing correlated with TIL scores obtained by hematoxylin and eosin (H&E) staining. However, tumors with little or no lymphocytes by H&E contained up to 3.6 × 106 TCR DNA sequences, highlighting the sensitivity of the ImmunoSEQ platform. In this dataset, ipilimumab increased intratumoral T-cell density over time, whereas cryoablation ± ipilimumab diversified and remodeled the intratumoral T-cell clonal repertoire. Compared with monotherapy, cryoablation plus ipilimumab was associated with numerically greater numbers of peripheral blood and intratumoral T-cell clones expanding robustly following therapy. In conclusion, TCR sequencing correlates with H&E lymphocyte scoring and provides additional information on clonal diversity. These findings support further study of the use of TCR sequencing as a biomarker for T-cell responses to therapy and for the study of cryoimmunotherapy in early-stage breast cancer. Cancer Immunol Res; 4(10); 835-44. ©2016 AACR.

Published
2016

30. LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade

Author

Hickman, Amber, Koetsier, Joost, Kurtanich, Trevin, Nielsen, Michael C., Winn, Glenn, Wang, Yunfei, Bentebibel, Salah-Eddine, Shi, Leilei, Williams, Simone PunLeila, Haymaker, Cara, Chesson, Charles B., Faak, Faisal, Dominguez, Ana L., Jones, Richard, Kuiatse, Isere, Caivano, Amy R., Khounlo, Sayadeth, Warier, Navin D., Marathi, Upendra, Biediger, Robert V. MarkeRonald J., Craft, John W., Jr., Hwu, Patrick, Davies, Michael A., Woodside, Darren G., Vanderslice, Peter, Diab, Adi, Overwijk, Willem W., and Hailemichael, Yared

Subjects
Immunotherapy -- Physiological aspects, Integrins -- Physiological aspects -- Health aspects, Immunity -- Physiological aspects -- Health aspects, Cancer -- Care and treatment, Melanoma -- Models -- Physiological aspects -- Drug therapy, Health care industry
Abstract

The inability of [CD8.sup.+] effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti-programmed death 1-resistant (anti-PD-1-resistant) tumors, whereas combinatorial treatment with anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) increased [CD8.sup.+] Teff intratumoral sequestration and synergized in cooperation with neutrophils in inducing cancer regression. 7HP349 intratumoral [CD8.sup.+] Teff enrichment activity depended on CXCL12. We analyzed gene expression profiles using RNA from baseline and on treatment tumor samples of 14 melanoma patients. We identified baseline CXCL12 gene expression as possibly improving the likelihood or response to anti-CTLA-4 therapies. Our results provide a proof-of-principle demonstration that LFA-1 activation could convert a T cellexclusionary TME to a T cell-enriched TME through mechanisms involving cooperation with innate immune cells., Introduction Immune checkpoint blockade (ICB) Abs that target programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which are focused on activating and mobilizing the body's immune system [...]

Published
2022
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32. Combining radiation and immunotherapy: a new systemic therapy for solid tumors?

Author

Tang, Chad, Wang, Xiaohong, Soh, Hendrick, Seyedin, Steven, Cortez, Maria, Krishnan, Sunil, Massarelli, Erminia, Hong, David, Naing, Aung, Diab, Adi, Gomez, Daniel, Ye, Huiping, Heymach, John, Komaki, Ristuko, Allison, James, Sharma, Padmanee, and Welsh, James

Subjects
Animals, Antigens, Neoplasm, Combined Modality Therapy, Humans, Immune System, Immunotherapy, Mice, Neoplasms, Radiotherapy
Abstract

With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. Herein, we present a comprehensive overview of the early clinical and preclinical evidence behind this approach.

Published
2014

33. Phase III randomized trial evaluating tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with advanced refractory melanoma (ILLUMINATE 301).

Author

Diab, Adi, Ascierto, Paolo Antonio, Abdel-Wahab, Reham, Maio, Michele, Negrier, Sylvie, Mortier, Laurent, Dalle, Stéphane, Krajsova, Ivana, de la Cruz, Luis, Leccia, Marie Thérèse, Guida, Michele, Lebbe, Celeste, Grob, Jean-Jacques, Butler, Marcus O., In, Gino Kim, Chunduru, Srinivas, Rahimian, Shah, and Robert, Caroline

Published
2024
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35. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial

Author

Amaria, Rodabe N, Prieto, Peter A, Tetzlaff, Michael T, Reuben, Alexandre, Andrews, Miles C, Ross, Merrick I, Glitza, Isabella C, Cormier, Janice, Hwu, Wen-Jen, Tawbi, Hussein A, Patel, Sapna P, Lee, Jeffrey E, Gershenwald, Jeffrey E, Spencer, Christine N, Gopalakrishnan, Vancheswaran, Bassett, Roland, Simpson, Lauren, Mouton, Rosalind, Hudgens, Courtney W, Zhao, Li, Zhu, Haifeng, Cooper, Zachary A, Wani, Khalida, Lazar, Alexander, Hwu, Patrick, Diab, Adi, Wong, Michael K, McQuade, Jennifer L, Royal, Richard, Lucci, Anthony, Burton, Elizabeth M, Reddy, Sangeetha, Sharma, Padmanee, Allison, James, Futreal, Phillip A, Woodman, Scott E, Davies, Michael A, and Wargo, Jennifer A

Published
2018
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38. Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy

Author

Sharma, Meenu, Khong, Hiep, Fa’ak, Faisal, Bentebibel, Salah-Eddine, Janssen, Louise M. E., Chesson, Brent C., Creasy, Caitlin A., Forget, Marie-Andrée, Kahn, Laura Maria S., Pazdrak, Barbara, Karki, Binisha, Hailemichael, Yared, Singh, Manisha, Vianden, Christina, Vennam, Srinivas, Bharadwaj, Uddalak, Tweardy, David J., Haymaker, Cara, Bernatchez, Chantale, Huang, Shixia, Rajapakshe, Kimal, Coarfa, Cristian, Hurwitz, Michael E., Sznol, Mario, Hwu, Patrick, Hoch, Ute, Addepalli, Murali, Charych, Deborah H., Zalevsky, Jonathan, Diab, Adi, and Overwijk, Willem W.

Published
2020
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39. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Author

Amaria, Rodabe N., Reddy, Sangeetha M., Tawbi, Hussein A., Davies, Michael A., Ross, Merrick I., Glitza, Isabella C., Cormier, Janice N., Lewis, Carol, Hwu, Wen-Jen, Hanna, Ehab, Diab, Adi, Wong, Michael K., Royal, Richard, Gross, Neil, Weber, Randal, Lai, Stephen Y., Ehlers, Richard, Blando, Jorge, Milton, Denái R., Woodman, Scott, Kageyama, Robin, Wells, Daniel K., Hwu, Patrick, Patel, Sapna P., Lucci, Anthony, Hessel, Amy, Lee, Jeffrey E., Gershenwald, Jeffrey, Simpson, Lauren, Burton, Elizabeth M., Posada, Liberty, Haydu, Lauren, Wang, Linghua, Zhang, Shaojun, Lazar, Alexander J., Hudgens, Courtney W., Gopalakrishnan, Vancheswaran, Reuben, Alexandre, Andrews, Miles C., Spencer, Christine N., Prieto, Victor, Sharma, Padmanee, Allison, James, Tetzlaff, Michael T., and Wargo, Jennifer A.

Published
2018
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42. Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy

Author

Menon, Hari, Chen, Dawei, Ramapriyan, Rishab, Verma, Vivek, Barsoumian, Hampartsoum B., Cushman, Taylor R., Younes, Ahmed I., Cortez, Maria A., Erasmus, Jeremy J., de Groot, Patricia, Carter, Brett W., Hong, David S., Glitza, Isabella C., Ferrarotto, Renata, Altan, Mehmet, Diab, Adi, Chun, Stephen G., Heymach, John V., Tang, Chad, Nguyen, Quynh N., and Welsh, James W.

Published
2019
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44. Correction to: Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis

Author

Johnson, Daniel H., Zobniw, Chrystia M., Trinh, Van A., Ma, Junsheng, Bassett Jr, Roland L., Abdel-Wahab, Noha, Anderson, Jaime, Davis, Jennifer E., Joseph, Jocelyn, Uemura, Marc, Noman, Ali, Abu-Sbeih, Hamzah, Yee, Cassian, Amaria, Rodabe, Patel, Sapna, Tawbi, Hussein, Glitza, Isabella C., Davies, Michael A., Wong, Michael K., Woodman, Scott, Hwu, Wen-Jen, Hwu, Patrick, Wang, Yinghong, and Diab, Adi

Published
2019
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46. Infliximab for Treatment of Immune Adverse Events and Its Impact on Tumor Response.

Author

Parvathareddy, Vishnupriyadevi, Selamet, Umut, Sen, Aditi A., Mamlouk, Omar, Song, Juhee, Page, Valda D., Abdelrahim, Maen, Diab, Adi, Abdel-Wahab, Noha, and Abudayyeh, Ala

Subjects
PREVENTION of drug side effects, DISEASE progression, IMMUNE checkpoint inhibitors, INFLIXIMAB, RETROSPECTIVE studies, TREATMENT effectiveness, CANCER patients, KAPLAN-Meier estimator, RESEARCH funding, TUMORS, PROGRESSION-free survival, PATIENT safety, OVERALL survival, PROPORTIONAL hazards models, EVALUATION
Abstract

Simple Summary: The use of biologic agents in the treatment of immune adverse events (irAEs) due to immune checkpoint inhibitors has been an attractive option but there are limited data on their impact on tumor progression. This study is one of the largest retrospective cohorts that evaluated the predictors of response to infliximab for the treatment of irAEs and infliximab's impact on tumor response. The study helps to support the safe and effective use of infliximab in treatment of irAEs without significant impact on tumor response. Background: Immune-related adverse events (irAEs) challenge the use of immune checkpoint inhibitors (ICIs). We performed a retrospective study to evaluate response to infliximab for immune-related adverse event management, and infliximab's effect on progression-free survival (PFS) and overall survival (OS) with a focus on melanoma and genitourinary cancers. Methods: We retrospectively reviewed records of all cancer patients exposed to infliximab after immune checkpoint inhibitor (ICI) treatment from 2004 to 2021 at the MD Anderson Cancer Center. Survival was assessed utilizing the Kaplan–Meier method. Univariate and multivariate logistic regression was utilized to evaluate predictors of infliximab response, OS, and PFS. Results: We identified 185 cancer patients (93 melanoma and 37 genitourinary cancers) treated with ICI and who received infliximab to treat irAEs. Within 3 months of treatment initiation, 71% of the patients responded to infliximab, 27% had no response, and 2% had unknown response. Among different irAEs, colitis was associated with increased response to infliximab at 3 months, irrespective of the type of malignancy. We evaluated best tumor response before and after infliximab in the entire cohort and again in the melanoma and genitourinary (GU); the findings were similar in the melanoma cohort and the entire cohort, where best tumor response before and after infliximab was not significantly different. In the melanoma cohort, acute kidney injury (AKI) was associated with increased risk of death, p = 0.0109, and having response to infliximab was associated with decreased risk of death, p = 0.0383. Interestingly in GU cancer patients, myositis was associated with increased risk of death, p = 0.0041, and having a response to infliximab was marginally associated with decreased risk of death, p = 0.0992. As regards PFS, in a multivariate Cox regression model, having a history of cardiovascular disease remained significantly associated with shorter PFS in the melanoma cohort. For patients with GU cancers, response to infliximab was associated with longer PFS. Conclusions: Our study is among the largest retrospective analyses of infliximab use for irAE management. Patients with colitis were the best responders to infliximab. AKI before initiation of infliximab in the melanoma subcohort and myositis in GU subcohort are associated with higher risk of death. Our results indicate no association between infliximab and cancer progression with the exception of genitourinary cancers. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

Author

Diab, Adi, Gogas, Helen, Sandhu, Shahneen, Long, Georgina V., Ascierto, Paolo A., Larkin, James, Sznol, Mario, Franke, Fabio, Ciuleanu, Tudor E., Pereira, Caio, Muñoz Couselo, Eva, Bronzon Damian, Fernanda, Schenker, Michael, Perfetti, Aldo, Lebbe, Celeste, Quéreux, Gaëlle, Meier, Friedegund, Curti, Brendan D., Rojas, Carlos, and Arriaga, Yull

Published
2023
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48. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Author

Roh, Whijae, Chen, Pei-Ling, Reuben, Alexandre, Spencer, Christine N., Prieto, Peter A., Miller, John P., Gopalakrishnan, Vancheswaran, Wang, Feng, Cooper, Zachary A., Reddy, Sangeetha M., Gumbs, Curtis, Little, Latasha, Chang, Qing, Chen, Wei-Shen, Wani, Khalida, De Macedo, Mariana Petaccia, Chen, Eveline, Austin-Breneman, Jacob L., Jiang, Hong, Roszik, Jason, Tetzlaff, Michael T., Davies, Michael A., Gershenwald, Jeffrey E., Tawbi, Hussein, Lazar, Alexander J., Hwu, Patrick, Hwu, Wen-Jen, Diab, Adi, Glitza, Isabella C., Patel, Sapna P., Woodman, Scott E., Amaria, Rodabe N., Prieto, Victor G., Hu, Jianhua, Sharma, Padmanee, Allison, James P., Chin, Lynda, Zhang, Jianhua, Wargo, Jennifer A., and Futreal, P. Andrew

Published
2017
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50. Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis

Author

Johnson, Daniel H, Zobniw, Chrystia M, Trinh, Van A, Ma, Junsheng, Bassett, Jr, Roland L, Abdel-Wahab, Noha, Anderson, Jaime, Davis, Jennifer E, Joseph, Jocelyn, Uemura, Marc, Noman, Ali, Abu-Sbeih, Hamzah, Yee, Cassian, Amaria, Rodabe, Patel, Sapna, Tawbi, Hussein, Glitza, Isabella C, Davies, Michael A, Wong, Michael K, Woodman, Scott, Hwu, Wen-Jen, Hwu, Patrick, Wang, Yinghong, and Diab, Adi

Published
2018
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