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2,270 results on '"Richardson, Paul"'

105. Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity

Author

Pai, Chien-Chun Steven, Simons, Donald M., Lu, Xiaoqing, Evans, Michael, Wei, Junnian, Wang, Yung-hua, Chen, Mingyi, Huang, John, Park, Chanhyuk, Chang, Anthony, Wang, Jiaxi, Westmoreland, Susan, Beam, Christine, Banach, Dave, Bowley, Diana, Dong, Feng, Seagal, Jane, Ritacco, Wendy, Richardson, Paul L., Mitra, Soumya, Lynch, Grace, Bousquet, Pete, Mankovich, John, Kingsbury, Gillian, and Fong, Lawrence

Subjects
Immune response -- Research, Immunotherapy -- Usage, Ipilimumab -- Drug therapy, Melanoma -- Drug therapy -- Risk factors, Health care industry
Abstract

While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte-associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4-binding domain. Upon reaching the tumor, the outer domain was cleaved by membrane type-serine protease 1 (MT-SP1) present in the tumor microenvironment, leading to enhanced localization of CTLA4 blockade. Anti-CTLA4 DVD markedly reduced multiorgan immune toxicity by preserving tissue-resident Tregs in [Rag1.sup.-/-] mice that received naive donor [CD4.sup.+] T cells from WT C57BL/6j mice. Moreover, anti-CTLA4 DVD induced potent antitumor effects by decreasing tumor-infiltrating Tregs and increasing the infiltration of antigen-specific [CD8.sup.+] T lymphocytes in TRAMP-C2-bearing C57BL/6j mice. Treg depletion was mediated through the antibody-dependent cellular cytotoxicity (ADCC) mechanism, as anti-CTLA4 without the Fc[gamma]R-binding portion (anti- CTLA4 DANA) spared Tregs, preventing treatment-induced toxicities. In summary, our results demonstrate an approach to anti-CTLA4 blockade that depletes tumor-infiltrating, but not tissue-resident, Tregs, preserving antitumor effects while minimizing toxicity. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities., IntroductionImmune checkpoint inhibition (CPI) has demonstrated promising results in both preclinical models (1, 2) and in the clinic (3). Yet several issues remain and severely hinder the clinical benefits, including [...]

Published
2019
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111. Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma

Author

Samur, Mehmet Kemal, Minvielle, Stephane, Gulla, Annamaria, Fulciniti, Mariateresa, Cleynen, Alice, Aktas Samur, Anil, Szalat, Raphael, Shammas, Masood, Magrangeas, Florence, Tai, Yu-Tzu, Auclair, Daniel, Keats, Jonathan, Richardson, Paul, Attal, Michel, Moreau, Philippe, Anderson, Kenneth C., Parmigiani, Giovanni, Avet-Loiseau, Hervé, and Munshi, Nikhil C.

Published
2018
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112. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients

Author

Avet-Loiseau, Hervé, Bahlis, Nizar J., Chng, Wee-Joo, Masszi, Tamas, Viterbo, Luisa, Pour, Ludek, Ganly, Peter, Palumbo, Antonio, Cavo, Michele, Langer, Christian, Pluta, Andrzej, Nagler, Arnon, Kumar, Shaji, Ben-Yehuda, Dina, Rajkumar, S. Vincent, San-Miguel, Jesus, Berg, Deborah, Lin, Jianchang, van de Velde, Helgi, Esseltine, Dixie-Lee, di Bacco, Alessandra, Moreau, Philippe, and Richardson, Paul G.

Published
2017
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113. Consensus Report by Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees: Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 1: Focus on Investigations, Prophylaxis, and Specific Treatment

Author

Bajwa, Rajinder P.S., Mahadeo, Kris M., Taragin, Benjamin H., Dvorak, Christopher C., McArthur, Jennifer, Jeyapalan, Asumthia, Duncan, Christine N., Tamburro, Robert, Gehred, Alison, Lehmann, Leslie, Richardson, Paul, Auletta, Jeffery J., and Woolfrey, Ann E.

Published
2017
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118. The Genome of the Diatom Thalassiosira pseudonana: Ecology, Evolution, and Metabolism

Author

Armbrust, E. Virginia, Berges, John A., Bowler, Chris, Green, Beverley R., Martinez, Diego, Putnam, Nicholas H., Zhou, Shiguo, Allen, Andrew E., Apt, Kirk E., Bechner, Michael, Brzezinski, Mark A., Chaal, Balbir K., Chiovitti, Anthony, Davis, Aubrey K., Demarest, Mark S., Detter, J. Chris, Glavina, Tijana, Goodstein, David, Hadi, Masood Z., Hellsten, Uffe, Hildebrand, Mark, Jenkins, Bethany D., Jurka, Jerzy, Kapitonov, Vladimir V., Kröger, Nils, Lane, Todd W., Larimer, Frank W., Lippmeier, J. Casey, Lucas, Susan, Medina, Mónica, Montsant, Anton, Obornik, Miroslav, Parker, Micaela Schnitzler, Palenik, Brian, Pazour, Gregory J., Richardson, Paul M., Rynearson, Tatiana A., Saito, Mak A., Schwartz, David C., Thamatrakoln, Kimberlee, Valentin, Klaus, Vardi, Assaf, Wilkerson, Frances P., and Rokhsar, Daniel S.

Published
2004

120. Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Author

Gulick, Roy M., Wilkin, Timothy J., Chen, Ying Q., Landovitz, Raphael J., Amico, K. Rivet, Young, Alicia M., Richardson, Paul, Marzinke, Mark A., Hendrix, Craig W., Eshleman, Susan H., McGowan, Ian, Cottle, Leslie M., Andrade, Adriana, Marcus, Cheryl, Klingman, Karin L., Chege, Wairimu, Rinehart, Alex R., Rooney, James F., Andrew, Philip, Salata, Robert A., Magnus, Manya, Farley, Jason E., Liu, Albert, Frank, Ian, Ho, Ken, Santana, Jorge, Stekler, Joanne D., McCauley, Marybeth, and Mayer, Kenneth H.

Published
2017

121. Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma

Author

Hideshima, Teru, Qi, Jun, Paranal, Ronald M., Tang, Weiping, Greenberg, Edward, West, Nathan, Colling, Meaghan E., Estiu, Guillermina, Mazitschek, Ralph, Perry, Jennifer A., Ohguchi, Hiroto, Cottini, Francesca, Mimura, Naoya, Görgün, Güllü, Tai, Yu-Tzu, Richardson, Paul G., Carrasco, Ruben D., Wiest, Olaf, Schreiber, Stuart L., Anderson, Kenneth C., and Bradner, James E.

Published
2016

122. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma

Author

Paludo, Jonas, Mikhael, Joseph R., LaPlant, Betsy R., Halvorson, Alese E., Kumar, Shaji, Gertz, Morie A., Hayman, Suzanne R., Buadi, Francis K., Dispenzieri, Angela, Lust, John A., Kapoor, Prashant, Leung, Nelson, Russell, Stephen J., Dingli, David, Go, Ronald S., Lin, Yi, Gonsalves, Wilson I., Fonseca, Rafael, Bergsagel, P.Leif, Roy, Vivek, Sher, Taimur, Chanan-Khan, Asher A., Ailawadhi, Sikander, Stewart, A.Keith, Reeder, Craig B., Richardson, Paul G., Rajkumar, S.Vincent, and Lacy, Martha Q.

Published
2017
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123. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial

Author

Holstein, Sarah A, Jung, Sin-Ho, Richardson, Paul G, Hofmeister, Craig C, Hurd, David D, Hassoun, Hani, Giralt, Sergio, Stadtmauer, Edward A, Weisdorf, Daniel J, Vij, Ravi, Moreb, Jan S, Callander, Natalie S, van Besien, Koen, Gentile, Teresa G, Isola, Luis, Maziarz, Richard T, Bashey, Asad, Landau, Heather, Martin, Thomas, Qazilbash, Muzaffar H, Rodriguez, Cesar, McClune, Brian, Schlossman, Robert L, Smith, Scott E, Hars, Vera, Owzar, Kouros, Jiang, Chen, Boyd, Molly, Schultz, Chelsea, Wilson, Marcia, Hari, Parameswaran, Pasquini, Marcelo C, Horowitz, Mary M, Shea, Thomas C, Devine, Steven M, Linker, Charles, Anderson, Kenneth C, and McCarthy, Philip L

Published
2017
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124. Prognostic Validation of SKY92 and Its Combination With ISS in an Independent Cohort of Patients With Multiple Myeloma

Author

van Beers, Erik H., van Vliet, Martin H., Kuiper, Rowan, de Best, Leonie, Anderson, Kenneth C., Chari, Ajai, Jagannath, Sundar, Jakubowiak, Andrzej, Kumar, Shaji K., Levy, Joan B., Auclair, Daniel, Lonial, Sagar, Reece, Donna, Richardson, Paul, Siegel, David S., Stewart, A. Keith, Trudel, Suzanne, Vij, Ravi, Zimmerman, Todd M., and Fonseca, Rafael

Published
2017
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126. The Draft Genome of Ciona intestinalis: Insights into Chordate and Vertebrate Origins

Author

Dehal, Paramvir, Satou, Yutaka, Campbell, Robert K., Chapman, Jarrod, Degnan, Bernard, de Tomaso, Anthony, Davidson, Brad, Di Gregorio, Anna, Gelpke, Maarten, Goodstein, David M., Harafuji, Naoe, Ho, Isaac, Hotta, Kohji, Huang, Wayne, Kawashima, Takeshi, Lemaire, Patrick, Martinez, Diego, Meinertzhagen, Ian A., Necula, Simona, Nonaka, Masaru, Putnam, Nik, Rash, Sam, Saiga, Hidetoshi, Satake, Masanobu, Terry, Astrid, Yamada, Lixy, Wang, Hong-Gang, Awazu, Satoko, Azumi, Kaoru, Boore, Jeffrey, Branno, Margherita, Chin-bow, Stephen, DeSantis, Rosaria, Doyle, Sharon, Francino, Pilar, Keys, David N., Haga, Shinobu, Hayashi, Hiroko, Hino, Kyosuke, Imai, Kaoru S., Inaba, Kazuo, Kano, Shungo, Kobayashi, Kenji, Kobayashi, Mari, Lee, Byung-In, Makabe, Kazuhiro W., Manohar, Chitra, Matassi, Giorgio, Medina, Monica, Mochizuki, Yasuaki, Mount, Steve, Morishita, Tomomi, Miura, Sachiko, Nakayama, Akie, Nishizaka, Satoko, Nomoto, Hisayo, Ohta, Fumiko, Oishi, Kazuko, Rigoutsos, Isidore, Sano, Masako, Sasaki, Akane, Sasakura, Yasunori, Shoguchi, Eiichi, Spagnuolo, Antoinetta, Stainier, Didier, Suzuki, Miho M., Tassy, Olivier, Takatori, Naohito, Tokuoka, Miki, Yagi, Kasumi, Yoshizaki, Fumiko, Wada, Shuichi, Zhang, Cindy, Hyatt, P. Douglas, Larimer, Frank, Detter, Chris, Doggett, Norman, Glavina, Tijana, Hawkins, Trevor, Richardson, Paul, Lucas, Susan, Kohara, Yuji, Levine, Michael, Satoh, Nori, and Rokhsar, Daniel S.

Published
2002

128. Molecular Sequelae of Proteasome Inhibition in Human Multiple Myeloma Cells

Author

Mitsiades, Nicholas, Mitsiades, Constantine S., Poulaki, Vassiliki, Chauhan, Dharminder, Fanourakis, Galinos, Gu, Xuesong, Bailey, Charles, Joseph, Marie, Libermann, Towia A., Treon, Steven P., Munshi, Nikhil C., Richardson, Paul G., Hideshima, Teru, and Anderson, Kenneth C.

Published
2002

129. Whole-Genome Shotgun Assembly and Analysis of the Genome of Fugu rubripes

Author

Aparicio, Samuel, Chapman, Jarrod, Stupka, Elia, Putnam, Nik, Chia, Jer-ming, Dehal, Paramvir, Christoffels, Alan, Rash, Sam, Hoon, Shawn, Smit, Arian, Roach, Jared, Oh, Tania, Ho, Isaac Y., Wong, Marie, Detter, Chris, Verhoef, Frans, Predki, Paul, Tay, Alice, Lucas, Susan, Richardson, Paul, Smith, Sarah F., Clark, Melody S., Doggett, Norman, Zharkikh, Andrey, Tavtigian, Sean V., Pruss, Dmitry, Barnstead, Mary, Evans, Cheryl, Baden, Holly, Powell, Justin, Glusman, Gustavo, Rowen, Lee, Hood, Leroy, Tan, Y. H., Elgar, Greg, Hawkins, Trevor, Venkatesh, Byrappa, Rokhsar, Daniel, and Brenner, Sydney

Published
2002

130. Role of 18F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group

Author

Cavo, Michele, Terpos, Evangelos, Nanni, Cristina, Moreau, Philippe, Lentzsch, Suzanne, Zweegman, Sonja, Hillengass, Jens, Engelhardt, Monika, Usmani, Saad Z, Vesole, David H, San-Miguel, Jesus, Kumar, Shaji K, Richardson, Paul G, Mikhael, Joseph R, da Costa, Fernando Leal, Dimopoulos, Meletios-Athanassios, Zingaretti, Chiara, Abildgaard, Niels, Goldschmidt, Hartmut, Orlowski, Robert Z, Chng, Wee Joo, Einsele, Hermann, Lonial, Sagar, Barlogie, Bart, Anderson, Kenneth C, Rajkumar, S Vincent, Durie, Brian G M, and Zamagni, Elena

Published
2017
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134. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study

Author

Dimopoulos, Meletios A., Lonial, Sagar, White, Darrell, Moreau, Philippe, Weisel, Katja, San-Miguel, Jesus, Shpilberg, Ofer, Grosicki, Sebastian, Špička, Ivan, Walter-Croneck, Adam, Magen, Hila, Mateos, Maria-Victoria, Belch, Andrew, Reece, Donna, Beksac, Meral, Spencer, Andrew, Oakervee, Heather, Orlowski, Robert Z., Taniwaki, Masafumi, Röllig, Christoph, Einsele, Hermann, Matsumoto, Morio, Wu, Ka Lung, Anderson, Kenneth C., Jou, Ying-Ming, Ganetsky, Alex, Singhal, Anil K., and Richardson, Paul G.

Published
2020
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135. Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Author

Mouhieddine, Tarek H., Sperling, Adam S., Redd, Robert, Park, Jihye, Leventhal, Matthew, Gibson, Christopher J., Manier, Salomon, Nassar, Amin H., Capelletti, Marzia, Huynh, Daisy, Bustoros, Mark, Sklavenitis-Pistofidis, Romanos, Tahri, Sabrin, Hornburg, Kalvis, Dumke, Henry, Itani, Muhieddine M., Boehner, Cody J., Liu, Chia-Jen, AlDubayan, Saud H., Reardon, Brendan, Van Allen, Eliezer M., Keats, Jonathan J., Stewart, Chip, Mehr, Shaadi, Auclair, Daniel, Schlossman, Robert L., Munshi, Nikhil C., Anderson, Kenneth C., Steensma, David P., Laubach, Jacob P., Richardson, Paul G., Ritz, Jerome, Ebert, Benjamin L., Soiffer, Robert J., Trippa, Lorenzo, Getz, Gad, Neuberg, Donna S., and Ghobrial, Irene M.

Published
2020
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138. A chemical biology toolbox to study protein methyltransferases and epigenetic signaling

Author

Scheer, Sebastian, Ackloo, Suzanne, Medina, Tiago S., Schapira, Matthieu, Li, Fengling, Ward, Jennifer A., Lewis, Andrew M., Northrop, Jeffrey P., Richardson, Paul L., Kaniskan, H. Ümit, Shen, Yudao, Liu, Jing, Smil, David, McLeod, David, Zepeda-Velazquez, Carlos A., Luo, Minkui, Jin, Jian, Barsyte-Lovejoy, Dalia, Huber, Kilian V. M., De Carvalho, Daniel D., Vedadi, Masoud, Zaph, Colby, Brown, Peter J., and Arrowsmith, Cheryl H.

Published
2019
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139. Immunomodulation of NK, NKT and B/T cell subtypes in relapsed/refractory multiple myeloma patients treated with pomalidomide along with velcade and dexamethasone and its association with improved progression-free survival.

Author

Prabhala, Rao, Pierceall, William E., Samur, Mehmet, Potluri, Lakshmi B., Hong, Kevin, Peluso, Teresa, Talluri, Srikanth, Wang, Angela, Katiki, Aishwarya, Vangala, Sahan D., Buonopane, Michael, Bade, Vaishnavi, Seah, Hannah, Krogman, Arthur, Derebail, Sanika, Fulciniti, Mariateresa, Lazo, Suzan B., Richardson, Paul, Anderson, Kenneth, and Corre, Jill

Subjects
T cells, MULTIPLE myeloma, PROGRESSION-free survival, KILLER cells, BIOMARKERS
Abstract

Background: Multiple Myeloma (MM) patients exhibit dysregulated immune system, which is further weakened by chemotherapeutic agents. While cereblon-modulating agents, such as pomalidomide and lenalidomide, have been found to improve the immune profile, the efficacy of their impact in combination with other treatments is yet unknown. Methods: We conducted an immune-profiling of a longitudinal cohort of 366 peripheral blood samples from the CC4047-MM-007 (OPTIMISMM, NCT01734928) study. This study followed relapsed/refractory Multiple Myeloma (RRMM) patients who were treated with Velcade + dexamethasone (Vd), or Vd with pomalidomide (PVd). 366 blood samples from 186 patients were evaluated using multi-color flow cytometry at 3 timepoints: screening, day 8 of cycle 1, and cycle 3. Results: Among NK and NKT cell populations, adding pomalidomide showed no inhibition in the frequency of NK cells. When expression of double positivity for activation markers like, p46/NKG2D, on NK cells was higher than the median, PVd treated patients showed significantly better (p=0.05) progression-free survival (PFS) (additional 15 months) than patients with lower than the median expression of p46/NKG2D on NK cells. PVd treated patients who expressed CD158a/b below the median at cycle 1 demonstrated a significantly better PFS (more than 18months). Among B cell subtypes, PVd treatment significantly increased the abundance of B1b cells (p<0.05) and decreased Bregs (p<0.05) at day 8 of both cycle 1 and cycle 3 when compared to screening samples. Of all the B cell-markers evaluated among paired samples, a higher expression of MZB cells at day 8 of cycle 1 has resulted in enhanced PFS in PVd treated patients. Within T cells, pomalidomide treatment did not decrease the frequency of CD8 T cells when compared with screening samples. The higher the surface expression of OX-40 on CD8 T cells and the lower the expression of PD-1 and CD25 on CD4 T cells by PVd treatment resulted in improved PFS. Conclusion: The prognostic significance for the number of immune markers is only seen in the PVd arm and none of these immune markers exhibit prognostic values in the Vd arm. This study demonstrates the importance of the immunomodulatory effects and the therapeutic benefit of adding pomalidomide to Vd treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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140. Guidelines for the Use and Reporting of Patient-Reported Outcomes in Multiple Myeloma Clinical Trials.

Author

Laane, Edward, Salek, Sam, Oliva, Esther Natalie, Bennink, Christine, Clavreul, Solène, Richardson, Paul G, Scheid, Christof, Weisel, Katja, and Ionova, Tatyana

Subjects
MULTIPLE myeloma treatment, CLINICAL trials, PATIENT autonomy, STRATEGIC planning, GLOBAL burden of disease, HEMATOLOGY, HEALTH outcome assessment, MEDICAL protocols, TREATMENT effectiveness, HUMAN services programs, QUALITY of life, DISEASE remission, GOAL (Psychology)
Abstract

Simple Summary: It is recognized that patients with multiple myeloma (MM) experience a high burden of disease and treatment-related symptoms that impact upon their quality of life (QoL). In these patients, patient-reported outcome (PRO) measures are important in providing information on how treatment affects their QoL. In the past 10 years in the MM setting, the main focus has been to achieve the most durable remission with the best QoL as primary goals of therapy. Optimizing the QoL of patients with MM is an important treatment goal and the use of PROs in clinical trials has the potential to improve treatment outcomes. The present report, on behalf of the European Hematology Association (EHA), provides evidence-based guidelines for the use and reporting of PROs in patients with MM that have been developed according to the EHA's core Guidelines Development Methodology. Currently, there is considerable variation in the measurement of QoL in MM trials, thus underlining the importance of systematic measurements. These Guidelines will aid clinicians, regulatory agencies and the pharmaceutical industry in the measurement of QoL in patients with MM in clinical trials. In the era of personalized medicine there is an increasing need for the assessment of patient-reported outcomes (PROs) to become a standard of patient care. Patient-reported outcome measures (PROM) are important in assessing significant and meaningful changes as a result of an intervention based on a patient's own perspective. It is well established that active multiple myeloma (MM) can be characterized by a high burden of disease and treatment-related symptoms, with considerable worsening of quality of life (QoL). In general, and over the past decade, the focus has shifted to obtaining the most durable remissions with the best QoL as primary goals for MM treatment. Patients place considerable value on their QoL and communicating about QoL data prior to treatment decisions allows them to make informed treatment choices. Consequently, optimization of QoL of patients with MM is an important therapeutic goal and the incorporation of PROs into clinical trials has the potential of improving treatment outcomes. In this regard, guidance for the use and reporting of PROMs in MM in clinical trials is warranted. Under the auspices of the European Hematology Association, evidence-based guidelines for the use and reporting of PROs in patients with MM have been developed according to the EHA's core Guidelines Development Methodology. This document provides general considerations for the choice of PROMs in MM clinical trials as well as a series of recommendations covering a selection of PROMs in MM clinical trials; the mode of administration; timing of assessments; strategies to minimize missing data; sample size calculation; reporting of results; and interpretation of results. [ABSTRACT FROM AUTHOR]

Published
2023
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141. Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy.

Author

Mo, Clifton C., Hartley-Brown, Monique A., Midha, Shonali, and Richardson, Paul G.

Subjects
STEM cell transplantation, MULTIPLE myeloma treatment, MULTIPLE myeloma diagnosis, MELPHALAN, AUTOGRAFTS, TREATMENT effectiveness, PROGRESSION-free survival, INDUCTION chemotherapy, OVERALL survival
Abstract

Simple Summary: Patients who are diagnosed with multiple myeloma are given an initial sequence of treatments that usually, for those who are young and fit enough, includes high-dose melphalan followed by autologous stem cell transplantation. This has contributed to the improvement in survival seen over the past 30 years. However, high-dose melphalan has significant limitations, including short-term side effects and longer-term issues such as an increased risk of developing secondary hematologic malignancies including leukemia. There are now numerous highly efficacious combination regimens for initial treatment that result in increasingly large proportions of patients achieving deep responses with no evidence of minimal residual disease. Moreover, large, randomized studies using these regimens have shown no benefit in overall survival after receiving high-dose melphalan with stem cell transplantation. There is thus a growing rationale for selected eligible patients to defer receiving high-dose melphalan and stem cell transplantation until potentially needed in a subsequent line of treatment. The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT. [ABSTRACT FROM AUTHOR]

Published
2023
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142. In severe alcohol‐related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL‐8 and micro‐RNAs.

Author

Tyson, Luke D., Atkinson, Stephen, Hunter, Robert W., Allison, Michael, Austin, Andrew, Dear, James W., Forrest, Ewan, Liu, Tong, Lord, Emma, Masson, Steven, Nunes, Joao, Richardson, Paul, Ryder, Stephen D., Wright, Mark, Thursz, Mark, and Vergis, Nikhil

Subjects
ACUTE kidney failure, MICRORNA, LIVER diseases, HEPATITIS, MORTALITY, KIDNEYS
Abstract

Summary: Background: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol‐related hepatitis (AH) is uncertain. Aims: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date. Methods: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0‐AKI. Survival was compared by Kaplan–Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses. Results: D0‐AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0‐AKI had higher 90‐day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0‐AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56–2.97, p < 0.001); D0‐AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36–0.85, p = 0.007) but not mortality. D0 bilirubin and IL‐8 combined, miR‐6826‐5p, and miR‐6811‐3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01). Conclusions: Incident AKI is associated with 90‐day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL‐8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality. [ABSTRACT FROM AUTHOR]

Published
2023
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143. Green Chemistry Articles of Interest to the Pharmaceutical Industry.

Author

Ashley, Melissa A., Aukland, Miles H., Bryan, Marian C., Cismesia, Megan A., Engl, Oliver D., Engl, Pascal S., Garcia, Álvaro Enriquez, Molina, Alejandro Gimenez, Karageorgis, George, Kelly, Christopher B., Leclair, Alexandre, Li, Wei, Pawlas, Jan, Richardson, Paul F., Steven, Alan, Takale, Balaram S., Zeng, Mingshuo, and Zhang, Yongda

Published
2023
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144. Late versus early response and depth of response are associated with improved outcomes in patients with newly diagnosed multiple myeloma enrolled in the TOURMALINE‐MM2 trial.

Author

Richardson, Paul G., Facon, Thierry, Venner, Christopher P., Bahlis, Nizar J., Offner, Fritz, White, Darrell, Karlin, Lionel, Benboubker, Lotfi, Voog, Eric, Yoon, Sung‐Soo, Suzuki, Kenshi, Shibayama, Hirohiko, Zhang, Xiaoquan, Villarreal, Miguel, Twumasi‐Ankrah, Philip, Labotka, Richard, Rifkin, Robert M., Lonial, Sagar, Kumar, Shaji K., and Rajkumar, S. Vincent

Published
2023
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147. Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial

Author

San-Miguel, Jesús F, Hungria, Vania T M, Yoon, Sung-Soo, Beksac, Meral, Dimopoulos, Meletios A, Elghandour, Ashraf, Jedrzejczak, Wieslaw W, Günther, Andreas, Nakorn, Thanyaphong N, Siritanaratkul, Noppadol, Schlossman, Robert L, Hou, Jian, Moreau, Philippe, Lonial, Sagar, Lee, Jae H, Einsele, Hermann, Sopala, Monika, Bengoudifa, Bourras-Rezki, Binlich, Florence, and Richardson, Paul G

Published
2016
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149. Regional differences between people who inject drugs in an HIV prevention trial integrating treatment and prevention (HPTN 074): a baseline analysis

Author

Lancaster, Kathryn E., Hoffman, Irving F., Hanscom, Brett, Ha, Tran Viet, Dumchev, Kostyantyn, Susami, Hepa, Rose, Scott, Go, Vivian F., Reifeis, Sarah A., Mollan, Katie R., Hudgens, Michael G., Piwowar-Manning, Estelle M., Richardson, Paul, Dvoriak, Sergii, Djoerban, Zubairi, Kiriazova, Tetiana, Zeziulin, Oleksandr, Djauzi, Samsuridjal, Viet Ahn, Chu, Latkin, Carl, Metzger, David, Burns, David N., Sugarman, Jeremy, Strathdee, Steffanie A., Eshleman, Susan H., Clarke, William, Donnell, Deborah, Emel, Lynda, Sunner, Lisa E., McKinstry, Laura, Sista, Nirupama, Hamilton, Erica L., Lucas, Jonathan P., Duong, Bui D., Vuong, Nguyen Van, Sarasvita, Riza, and Miller, William C.

Subjects
Intravenous drug abuse -- Complications and side effects -- Demographic aspects, HIV infections -- Risk factors -- Demographic aspects -- Care and treatment, Medical geography -- Research, Health
Abstract

Introduction: People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention. Methods: We present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two-arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV-positive index and their HIV-negative network injection partner (s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours. Results: The majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self-reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test--Alcohol Consumption Questions (AUDIT-C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions. Conclusions: While regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations. Keywords: injection drug use; PWID; HIV; substance use treatment; ART; treatment as prevention, 1 | INTRODUCTION HIV epidemics in eastern Europe, central Asia and many parts of South East Asia are concentrated among people who inject drugs (PWID) [1]. Serial use and sharing [...]

Published
2018
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