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4. Real-world impact of bridging therapy on outcomes of ide-cel for myeloma in the U.S. Myeloma Immunotherapy Consortium

Author

Afrough, Aimaz, Hashmi, Hamza, Hansen, Doris K., Sidana, Surbhi, Ahn, Chul, Peres, Lauren C., Dima, Danai, Freeman, Ciara L., Puglianini, Omar Castaneda, Kocoglu, Mehmet H., Atrash, Shebli, Voorhees, Peter M., Shune, Leyla, McGuirk, Joseph P., Simmons, Gary, Sborov, Douglas W., Davis, James A., Kaur, Gurbakhash, Sannareddy, Aishwarya, Ferreri, Christopher J., Gaballa, Mahmoud R., Goldsmith, Scott, Nadeem, Omar, Midha, Shonali, Wagner, Charlotte B., Locke, Frederick L., Patel, Krina K., Khouri, Jack, Anderson, Jr., Larry D., and Lin, Yi

Published
2024
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6. Characterizing dry mass and volume changes in human multiple myeloma cells upon treatment with proteotoxic and genotoxic drugs.

Author

Liu, Xili, Moscvin, Maria, Chen, Tianzeng, Choi, Wonshik, Evans, Benjamin, Rowell, Sean, Nadeem, Omar, Mo, Clifton, Sperling, Adam, Anderson, Kenneth, Yaqoob, Zahid, Bianchi, Giada, Sung, Yongjin, and Oh, Seungeun

Subjects
Apoptosis, Cell dry mass, Label-free biomarkers, Multiple myeloma, Proteasome inhibitors, Humans, Bortezomib, Multiple Myeloma, Cell Line, Tumor, Proteasome Inhibitors, DNA Damage, Antineoplastic Agents, Apoptosis
Abstract

Multiple myeloma (MM) is a cancer of terminally differentiated plasma cells. MM remains incurable, but overall survival of patients has progressively increased over the past two decades largely due to novel agents such as proteasome inhibitors (PI) and the immunomodulatory agents. While these therapies are highly effective, MM patients can be de novo resistant and acquired resistance with prolonged treatment is inevitable. There is growing interest in early, accurate identification of responsive versus non-responsive patients; however, limited sample availability and need for rapid assays are limiting factors. Here, we test dry mass and volume as label-free biomarkers to monitor early response of MM cells to treatment with bortezomib, doxorubicin, and ultraviolet light. For the dry mass measurement, we use two types of phase-sensitive optical microscopy techniques: digital holographic tomography and computationally enhanced quantitative phase microscopy. We show that human MM cell lines (RPMI8226, MM.1S, KMS20, and AMO1) increase dry mass upon bortezomib treatment. This dry mass increase after bortezomib treatment occurs as early as 1 h for sensitive cells and 4 h for all tested cells. We further confirm this observation using primary multiple myeloma cells derived from patients and show that a correlation exists between increase in dry mass and sensitivity to bortezomib, supporting the use of dry mass as a biomarker. The volume measurement using Coulter counter shows a more complex behavior; RPMI8226 cells increase the volume at an early stage of apoptosis, but MM.1S cells show the volume decrease typically observed with apoptotic cells. Altogether, this cell study presents complex kinetics of dry mass and volume at an early stage of apoptosis, which may serve as a basis for the detection and treatment of MM cells.

Published
2023

7. Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma

Author

Sidana, Surbhi, Patel, Krina K., Peres, Lauren C., Bansal, Radhika, Kocoglu, Mehmet H., Shune, Leyla, Atrash, Shebli, Smith, Kinaya, Midha, Shonali, Ferreri, Christopher, Dhakal, Binod, Dima, Danai, Costello, Patrick, Wagner, Charlotte, Reshef, Ran, Hosoya, Hitomi, Mikkilineni, Lekha, Atanackovic, Djordje, Chhabra, Saurabh, Parrondo, Ricardo, Nadeem, Omar, Mann, Hashim, Kalariya, Nilesh, Hovanky, Vanna, De Avila, Gabriel, Freeman, Ciara L., Locke, Frederick L., Alsina, Melissa, Wong, Sandy, Herr, Megan, Htut, Myo, McGuirk, Joseph, Sborov, Douglas W., Khouri, Jack, Martin, Thomas, Janakiram, Murali, Lin, Yi, and Hansen, Doris K.

Published
2025
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10. Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy

Author

Ferreri, Christopher J., Hildebrandt, Michelle A. T., Hashmi, Hamza, Shune, Leyla O., McGuirk, Joseph P., Sborov, Douglas W., Wagner, Charlotte B., Kocoglu, M. Hakan, Rapoport, Aaron, Atrash, Shebli, Voorhees, Peter M., Khouri, Jack, Dima, Danai, Afrough, Aimaz, Kaur, Gurbakhash, Anderson, Jr., Larry D., Simmons, Gary, Davis, James A., Kalariya, Nilesh, Peres, Lauren C., Lin, Yi, Janakiram, Murali, Nadeem, Omar, Alsina, Melissa, Locke, Frederick L., Sidana, Surbhi, Hansen, Doris K., Patel, Krina K., and Castaneda Puglianini, Omar Alexis

Published
2023
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11. Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy

Author

Peres, Lauren C., Oswald, Laura B., Dillard, Christen M., De Avila, Gabriel, Nishihori, Taiga, Blue, Brandon J., Freeman, Ciara L., Locke, Frederick L., Alsina, Melissa, Castaneda Puglianini, Omar, Shune, Leyla, Sborov, Douglas W., Wagner, Charlotte, Dima, Danai, Hashmi, Hamza, Davis, James A., Kocoglu, Mehmet H., Badros, Ashraf Z., Atrash, Shebli, Simmons, Gary, Kalariya, Nilesh, Ferreri, Christopher, Anderson, Larry D., Jr, Afrough, Aimaz, Kaur, Gurbakhash, Lin, Yi, Liu, Lawrence, Nadeem, Omar, Voorhees, Peter, Khouri, Jack, McGuirk, Joseph, Sidana, Surbhi, Hansen, Doris K., and Patel, Krina

Published
2024
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12. Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma

Author

Yee, Andrew J., Laubach, Jacob P., Campagnaro, Erica L., Lipe, Brea C., Nadeem, Omar, Friedman, Robb S., Cole, Craig E., O’Donnell, Elizabeth K., Bianchi, Giada, Branagan, Andrew R., Schlossman, Robert L., Shapiro, Samantha J., Harrington, Cynthia C., Burke, Jill N., Gammon, Marilyn T., Lively, Kathleen J., Reimonn, Cassandra A., Andrade, Danielle X., Redd, Robert, Lohr, Jens G., Anderson, Kenneth C., Richardson, Paul G., and Raje, Noopur S.

Published
2024
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16. Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study

Author

Cowan, Annie, Ferrari, Federico, Freeman, Samuel S, Redd, Robert, El-Khoury, Habib, Perry, Jacqueline, Patel, Vidhi, Kaur, Priya, Barr, Hadley, Lee, David J, Lightbody, Elizabeth, Downey, Katelyn, Argyelan, David, Theodorakakou, Foteini, Fotiou, Despina, Liacos, Christine Ivy, Kanellias, Nikolaos, Chavda, Selina J, Ainley, Louise, Sandecká, Viera, Pospíšilová, Lenka, Minarik, Jiri, Jungova, Alexandra, Radocha, Jakub, Spicka, Ivan, Nadeem, Omar, Yong, Kwee, Hájek, Roman, Kastritis, Efstathios, Marinac, Catherine R, Dimopoulos, Meletios A, Getz, Gad, Trippa, Lorenzo, and Ghobrial, Irene M

Published
2023
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17. Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma

Author

Sklavenitis-Pistofidis, Romanos, Aranha, Michelle P., Redd, Robert A., Baginska, Joanna, Haradhvala, Nicholas J., Hallisey, Margaret, Dutta, Ankit K., Savell, Alexandra, Varmeh, Shohreh, Heilpern-Mallory, Daniel, Ujwary, Sylvia, Zavidij, Oksana, Aguet, Francois, Su, Nang K., Lightbody, Elizabeth D., Bustoros, Mark, Tahri, Sabrin, Mouhieddine, Tarek H., Wu, Ting, Flechon, Lea, Anand, Shankara, Rosenblatt, Jacalyn M., Zonder, Jeffrey, Vredenburgh, James J., Boruchov, Adam, Bhutani, Manisha, Usmani, Saad Z., Matous, Jeffrey, Yee, Andrew J., Jakubowiak, Andrzej, Laubach, Jacob, Manier, Salomon, Nadeem, Omar, Richardson, Paul, Badros, Ashraf Z., Mateos, Maria-Victoria, Trippa, Lorenzo, Getz, Gad, and Ghobrial, Irene M.

Published
2022
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19. Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience

Author

Khouri, Jack, Dima, Danai, Li, Hong, Hansen, Doris, Sidana, Surbhi, Shune, Leyla, Anwer, Faiz, Sborov, Douglas, Wagner, Charlotte, Kocoglu, Mehmet H., Atrash, Shebli, Voorhees, Peter, Peres, Lauren, Hovanky, Vanna, Simmons, Gary, Williams, Louis, Raza, Shahzad, Afrough, Aimaz, Anderson, Larry D., Jr, Ferreri, Christopher, Hashmi, Hamza, Davis, James, McGuirk, Joseph, Goldsmith, Scott, Borogovac, Azra, Lin, Yi, Midha, Shonali, Nadeem, Omar, Locke, Frederick L., Baz, Rachid, Hamilton, Betty, Alsina, Melissa, Sauter, Craig, Patel, Krina, and Kaur, Gurbakhash

Published
2024
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20. Quality of life, psychological distress, and prognostic perceptions in caregivers of patients with multiple myeloma

Author

O'Donnell, Elizabeth K., Shapiro, Yael N., Yee, Andrew J., Nadeem, Omar, Laubach, Jacob P., Branagan, Andrew R., Anderson, Kenneth C., Mo, Clifton C., Munshi, Nikhil C., Ghobrial, Irene M., Sperling, Adam S., Agyemang, Emerentia A., Burke, Jill N., Harrington, Cynthia C., Hu, Bonnie Y., Richardson, Paul G., Raje, Noopur S., and El-Jawahri, Areej

Published
2022
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21. Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Author

Nadeem, Omar, Aranha, Michelle P., Redd, Robert, Timonian, Michael, Magidson, Sophie, Lightbody, Elizabeth D., Alberge, Jean-Baptiste, Bertamini, Luca, Dutta, Ankit K., El-Khoury, Habib, Bustoros, Mark, Laubach, Jacob P., Bianchi, Giada, O'Donnell, Elizabeth, Wu, Ting, Tsuji, Junko, Anderson, Kenneth C., Getz, Gad, Trippa, Lorenzo, and Richardson, Paul G.

Subjects
T cells, GENE expression, PROGRESSION-free survival, RNA sequencing, MULTIPLE myeloma
Abstract

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10-5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes. Depth of response (CR/VGPR, MRD-) links to better outcomes, while biochemical progression predicts end-organ damage. Higher MHC-I on tumors and greater GZMB+ T cells in clonally expanded CD8+ T cells are tied to improved outcomes. [ABSTRACT FROM AUTHOR]

Published
2025
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22. Measurement error and bias in real-world oncology endpoints when constructing external control arms.

Author

Ackerman, Benjamin, Gan, Ryan W., Meyer, Craig S., Wang, Jocelyn R., Zhang, Youyi, Hayden, Jennifer, Mahoney, Grace, Lund, Jennifer L., Weberpals, Janick, Schneeweiss, Sebastian, Roose, James, Siddique, Juned, Nadeem, Omar, Giri, Smith, Stürmer, Til, Ailawadhi, Sikander, Batavia, Ashita S., and Sarsour, Khaled

Subjects
MEASUREMENT errors, PROGRESSION-free survival, MULTIPLE myeloma, TREATMENT effectiveness, COMPARATOR circuits
Abstract

Introduction: While randomized controlled trials remain the reference standard for evaluating treatment efficacy, there is an increased interest in the use of external control arms (ECA), namely in oncology, using real-world data (RWD). Challenges related to measurement of real-world oncology endpoints, like progression-free survival (PFS), are one factor limiting the use and acceptance of ECAs as comparators to trial populations. Differences in how and when disease assessments occur in the real-world may introduce measurement error and limit the comparability of real-world PFS (rwPFS) to trial progression-free survival. While measurement error is a known challenge when conducting an externally-controlled trial with real-world data, there is limited literature describing key contributing factors, particularly in the context of multiple myeloma (MM). Methods: We distinguish between biases attributed to how endpoints are derived or ascertained (misclassification bias) and when outcomes are observed or assessed (surveillance bias). We further describe how misclassification of progression events (i.e., false positives, false negatives) and irregular assessment frequencies in multiple myeloma RWD can contribute to these biases, respectively. We conduct a simulation study to illustrate how these biases may behave, both individually and together. Results: We observe in simulation that certain types of measurement error may have more substantial impacts on comparability between mismeasured median PFS (mPFS) and true mPFS than others. For instance, when the observed progression events are misclassified as either false positives or false negatives, mismeasured mPFS may be biased towards earlier (mPFS bias = −6.4 months) or later times (mPFS bias = 13 months), respectively. However, when events are correctly classified but assessment frequencies are irregular, mismeasured mPFS is more similar to the true mPFS (mPFS bias = 0.67 months). Discussion: When misclassified progression events and irregular assessment times occur simultaneously, they may generate bias that is greater than the sum of their parts. Improved understanding of endpoint measurement error and how resulting biases manifest in RWD is important to the robust construction of ECAs in oncology and beyond. Simulations that quantify the impact of measurement error can help when planning for ECA studies and can contextualize results in the presence of endpoint measurement differences. [ABSTRACT FROM AUTHOR]

Published
2024
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24. miR-15a/16-1 deletion in activated B cells promotes plasma cell and mature B-cell neoplasms

Author

Sewastianik, Tomasz, Straubhaar, Juerg R., Zhao, Jian-Jun, Samur, Mehmet K., Adler, Keith, Tanton, Helen E., Shanmugam, Vignesh, Nadeem, Omar, Dennis, Peter S., Pillai, Vinodh, Wang, Jianli, Jiang, Meng, Lin, Jianhong, Huang, Ying, Brooks, Daniel, Bouxsein, Mary, Dorfman, David M., Pinkus, Geraldine S., Robbiani, Davide F., Ghobrial, Irene M., Budnik, Bogdan, Jarolim, Petr, Munshi, Nikhil C., Anderson, Kenneth C., and Carrasco, Ruben D.

Published
2021
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27. Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma

Author

Ghobrial, Irene M., primary, Gormley, Nicole, additional, Kumar, Shaji K., additional, Mateos, Maria-Victoria, additional, Bergsagel, P. Leif, additional, Chesi, Marta, additional, Dhodapkar, Madhav V., additional, Dispenzieri, Angela, additional, Fonseca, Rafael, additional, Getz, Gad, additional, Kastritis, Efstathios, additional, Kristinsson, Sigurdur Y., additional, Martinez-Climent, Jose Angel, additional, Manier, Salomon, additional, Marinac, Catherine R., additional, Maura, Francesco, additional, Morgan, Gareth J., additional, Davies, Faith E., additional, Nadeem, Omar, additional, Nuvolone, Mario, additional, Paiva, Bruno, additional, O’Donnell, Elizabeth, additional, Prosper, Felipe, additional, Shah, Urvi A., additional, Sklavenitis-Pistofidis, Romanos, additional, Sperling, Adam S., additional, Vassiliou, George S., additional, Munshi, Nikhil C., additional, Castle, Philip E., additional, Anderson, Kenneth C., additional, and San Miguel, Jesus F., additional

Published
2024
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30. Progression-free survival as a surrogate endpoint in myeloma clinical trials:an evolving paradigm

Author

Pawlyn, Charlotte, Schjesvold, Fredrik H., Cairns, David A., Wei, L. J., Davies, Faith, Nadeem, Omar, Abdulhaq, Haifaa, Mateos, Maria Victoria, Laubach, Jacob, Weisel, Katja, Ludwig, Heinz, Rajkumar, S. Vincent, Sonneveld, Pieter, Jackson, Graham, Morgan, Gareth, Richardson, Paul G., Pawlyn, Charlotte, Schjesvold, Fredrik H., Cairns, David A., Wei, L. J., Davies, Faith, Nadeem, Omar, Abdulhaq, Haifaa, Mateos, Maria Victoria, Laubach, Jacob, Weisel, Katja, Ludwig, Heinz, Rajkumar, S. Vincent, Sonneveld, Pieter, Jackson, Graham, Morgan, Gareth, and Richardson, Paul G.

Abstract

Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.

Published
2024

32. Real-World Impact of Bridging Therapy on Outcomes of Ide-cel for Myeloma in the U.S. Myeloma Immunotherapy Consortium

Author

Afrough, Aimaz, primary, Hashmi, Hamza, additional, Hansen, Doris, additional, Sidana, Surbhi, additional, Ahn, Chul, additional, Peres, Lauren, additional, Dima, Danai, additional, Freeman, Ciara, additional, Puglianini, Omar Castaneda, additional, Kocoglu, Mehmet, additional, Atrash, Shebli, additional, Voorhees, Peter, additional, Shune, Leyla, additional, McGuirk, Joseph, additional, Simmons, Gary, additional, Sborov, Douglas, additional, Davis, James, additional, Kaur, Gurbakash, additional, Sannareddy, Aishwarya, additional, Ferreri, Christopher, additional, Gaballa, Mahmoud, additional, Janakiram, Murali, additional, nadeem, omar, additional, Midha, Shonali, additional, Wagner, Charlotte, additional, Locke, Frederick, additional, Patel, Krina, additional, Khouri, Jack, additional, Anderson, Larry, additional, and Lin, Yi, additional

Published
2023
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33. Supplementary Figures and Tables from MinimuMM-seq: Genome Sequencing of Circulating Tumor Cells for Minimally Invasive Molecular Characterization of Multiple Myeloma Pathology

Author

Dutta, Ankit K., primary, Alberge, Jean-Baptiste, primary, Lightbody, Elizabeth D., primary, Boehner, Cody J., primary, Dunford, Andrew, primary, Sklavenitis-Pistofidis, Romanos, primary, Mouhieddine, Tarek H., primary, Cowan, Annie N., primary, Su, Nang Kham, primary, Horowitz, Erica M., primary, Barr, Hadley, primary, Hevenor, Laura, primary, Beckwith, Jenna B., primary, Perry, Jacqueline, primary, Cao, Amanda, primary, Lin, Ziao, primary, Kuhr, Frank K., primary, Mastro, Richard G. Del, primary, Nadeem, Omar, primary, Greipp, Patricia T., primary, Stewart, Chip, primary, Auclair, Daniel, primary, Getz, Gad, primary, and Ghobrial, Irene M., primary

Published
2023
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34. Data from MinimuMM-seq: Genome Sequencing of Circulating Tumor Cells for Minimally Invasive Molecular Characterization of Multiple Myeloma Pathology

Author

Dutta, Ankit K., primary, Alberge, Jean-Baptiste, primary, Lightbody, Elizabeth D., primary, Boehner, Cody J., primary, Dunford, Andrew, primary, Sklavenitis-Pistofidis, Romanos, primary, Mouhieddine, Tarek H., primary, Cowan, Annie N., primary, Su, Nang Kham, primary, Horowitz, Erica M., primary, Barr, Hadley, primary, Hevenor, Laura, primary, Beckwith, Jenna B., primary, Perry, Jacqueline, primary, Cao, Amanda, primary, Lin, Ziao, primary, Kuhr, Frank K., primary, Mastro, Richard G. Del, primary, Nadeem, Omar, primary, Greipp, Patricia T., primary, Stewart, Chip, primary, Auclair, Daniel, primary, Getz, Gad, primary, and Ghobrial, Irene M., primary

Published
2023
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38. P-004 Expansion, persistence, and characteristics of autologous, BHV-1100 ARMored memory-like NK cells infused prior to autologous stem cell transplant in MRD+, newly diagnosed multiple myeloma patients

Author

Birch, Grace, primary, Vergara-Cadavid, Juliana, additional, Ansuinelli, Michela, additional, Nguyen, Tuyet, additional, Reynolds, Carol, additional, Im, Soo, additional, Wei, Hope, additional, Hogan, Sarah, additional, Kendricken, Elizabeth, additional, Sperling, Adam, additional, Nadeem, Omar, additional, Midha, Shonali, additional, Laubach, Jacob, additional, Rybicki, Alissa, additional, Schnittman, Steven, additional, Stock, Elyse, additional, Nikiforow, Sarah, additional, Ritz, Jerome, additional, Soiffer, Robert, additional, Bianchi, Giada, additional, and Romee, Rizwan, additional

Published
2023
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39. P-036 Real world single center expeirence of long-term toxicities with anti-BCMA CAR T-cell therapy in relapsed and refractory multiple myeloma

Author

Costello, Patrick, primary, Laubach, Jacob, additional, Mo, Clifton, additional, Sperling, Adam, additional, Nikiforow, Sarah, additional, Redd, Robert, additional, Ramsdell, Linda, additional, Finn, Kathleen, additional, Desnoyers, Lauren, additional, Denisco, Michelle, additional, Fraser, Esther, additional, Bianchi, Giada, additional, Hartley-Brown, Monique, additional, Ghobrial, Irene, additional, Richardson, Paul, additional, Anderson, Kenneth, additional, Munshi, Nikhil, additional, Nadeem, Omar, additional, and Midha, Shonali, additional

Published
2023
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40. P-037 BMS-986393 (CC-95266), a G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM): results from a phase 1 study

Author

Nadeem, Omar, primary, Berdeja, Jesus, additional, Htut, Myo, additional, Kocoglu, M Hakan, additional, Gregory, Tara, additional, Anderson, Larry, additional, Rossi, Adriana, additional, Egan, Daniel, additional, Costa, Luciano, additional, Kelly, Lisa, additional, Ziyad, Safiyyah, additional, Hu, Hongxiang, additional, Chen, Yanping, additional, Kaeding, Allison, additional, Burgess, Michael, additional, and Bal, Susan, additional

Published
2023
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41. P-099 Phase II trial of daratumumab, bortezomib, lenalidomide and dexamethasone in high-risk smoldering multiple myeloma

Author

Nadeem, Omar, primary, Redd, Robert, additional, Mo, Clifton, additional, Laubach, Jacob, additional, Richardson, Paul G., additional, Prescott, Julia, additional, Marto, Marjorie, additional, Davie, Christine, additional, Ricciardi, Caroline, additional, Murphy, Elizabeth, additional, Bertoni, Meredith, additional, Choden, Dechen, additional, Magidson, Sophie, additional, Sheehan, Brian, additional, Shrestha, Hira, additional, Sperling, Adam S., additional, O'Donnell, Elizabeth K., additional, and Ghobrial, Irene M., additional

Published
2023
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42. P-329 A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma

Author

Yee, Andrew, primary, Nadeem, Omar, additional, Rosenblatt, Jacalyn, additional, Sperling, Adam, additional, Bianchi, Giada, additional, Munshi, Nikhil, additional, O'Donnell, Elizabeth, additional, Branagan, Andrew, additional, Avigan, David, additional, Liegel, Jessica, additional, Harrington, Cynthia, additional, Agyemang, Emerentia, additional, Lively, Kathleen, additional, Packer, Lisette, additional, Han, Samuel, additional, Minsky, Cole, additional, Riadi, Manal, additional, McVey, Cailin, additional, Donnelly, Kaleigh, additional, Smith, Caitlin, additional, Katzeff, Mackenna, additional, Goguen, Amy, additional, Horick, Nora, additional, Richardson, Paul, additional, and Raje, Noopur, additional

Published
2023
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43. P-035 Real world experience of patients treated with teclistamab: a BCMA-directed bispecific T-cell engaging therapy for multiple myeloma

Author

Midha, Shonali, primary, Leblebjian, Houry, additional, Laubach, Jacob, additional, Mo, Clifton, additional, Sperling, Adam, additional, Nadeem, Omar, additional, Bianchi, Giada, additional, Hartley-Brown, Monique, additional, Ramsdell, Linda, additional, Donadio, Kristen, additional, Chun, Emerald, additional, Belanger, Megan, additional, Dobrusin, Irina, additional, Ghobrial, Irene, additional, Richardson, Paul, additional, Anderson, Kenneth, additional, and Munshi, Nikhil, additional

Published
2023
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44. S193: BMS-986393 (CC-95266), A G PROTEIN–COUPLED RECEPTOR CLASS C GROUP 5 MEMBER D (GPRC5D)–TARGETED CAR T-CELL THERAPY FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM A PHASE 1 STUDY

Author

Bal, Susan, primary, Berdeja, Jesus, additional, Htut, Myo, additional, Kocoglu, Mehmet, additional, Gregory, Tara, additional, Anderson, Larry D., additional, Rossi, Adriana, additional, Egan, Daniel, additional, Costa, Luciano, additional, Kelly, Lisa, additional, Ziyad, Safiyyah, additional, Hu, Hongxiang, additional, Chen, Yanping, additional, Kaeding, Allison J., additional, Burgess, Michael, additional, Hege, Kristen, additional, and Nadeem, Omar, additional

Published
2023
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47. Selinexor: Targeting a novel pathway in multiple myeloma

Author

Mo, Clifton C., primary, Yee, Andrew J., additional, Midha, Shonali, additional, Hartley‐Brown, Monique A., additional, Nadeem, Omar, additional, O'Donnell, Elizabeth K., additional, Bianchi, Giada, additional, Sperling, Adam S., additional, Laubach, Jacob P., additional, and Richardson, Paul G., additional

Published
2023
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48. Characterizing dry mass and volume changes in human multiple myeloma cells upon treatment with proteotoxic and genotoxic drugs

Author

Massachusetts Institute of Technology. Laser Biomedical Research Center, Liu, Xili, Moscvin, Maria, Oh, Seungeun, Chen, Tianzeng, Choi, Wonshik, Evans, Benjamin, Rowell, Sean M., Nadeem, Omar, Mo, Clifton C., Sperling, Adam S., Anderson, Kenneth C., Yaqoob, Zahid, Bianchi, Giada, Sung, Yongjin, Massachusetts Institute of Technology. Laser Biomedical Research Center, Liu, Xili, Moscvin, Maria, Oh, Seungeun, Chen, Tianzeng, Choi, Wonshik, Evans, Benjamin, Rowell, Sean M., Nadeem, Omar, Mo, Clifton C., Sperling, Adam S., Anderson, Kenneth C., Yaqoob, Zahid, Bianchi, Giada, and Sung, Yongjin

Abstract

Multiple myeloma (MM) is a cancer of terminally differentiated plasma cells. MM remains incurable, but overall survival of patients has progressively increased over the past two decades largely due to novel agents such as proteasome inhibitors (PI) and the immunomodulatory agents. While these therapies are highly effective, MM patients can be de novo resistant and acquired resistance with prolonged treatment is inevitable. There is growing interest in early, accurate identification of responsive versus non-responsive patients; however, limited sample availability and need for rapid assays are limiting factors. Here, we test dry mass and volume as label-free biomarkers to monitor early response of MM cells to treatment with bortezomib, doxorubicin, and ultraviolet light. For the dry mass measurement, we use two types of phase-sensitive optical microscopy techniques: digital holographic tomography and computationally enhanced quantitative phase microscopy. We show that human MM cell lines (RPMI8226, MM.1S, KMS20, and AMO1) increase dry mass upon bortezomib treatment. This dry mass increase after bortezomib treatment occurs as early as 1 h for sensitive cells and 4 h for all tested cells. We further confirm this observation using primary multiple myeloma cells derived from patients and show that a correlation exists between increase in dry mass and sensitivity to bortezomib, supporting the use of dry mass as a biomarker. The volume measurement using Coulter counter shows a more complex behavior; RPMI8226 cells increase the volume at an early stage of apoptosis, but MM.1S cells show the volume decrease typically observed with apoptotic cells. Altogether, this cell study presents complex kinetics of dry mass and volume at an early stage of apoptosis, which may serve as a basis for the detection and treatment of MM cells.

Published
2023

49. Multivariable Analyses of Prognostic Factors for Progression-Free Survival (PFS) and Complete Response (CR) with Lenalidomide, Bortezomib, and Dexamethasone (RVd) Alone Versus Rvd Plus Autologous Stem Cell Transplantation (ASCT) and Lenalidomide (R) Maintenance to Progression in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Determination Phase 3 Trial

Author

Hassoun, Hani, primary, Jacobus, Susanna J, additional, Richardson, Paul G., additional, Zonder, Jeffrey, additional, Voorhees, Peter M., additional, Kaufman, Jonathan L., additional, Yee, Andrew J, additional, Scott, Emma C, additional, Torka, Pallawi, additional, Libby, Edward N., additional, Reeves, Brandi, additional, Wang, Michael L., additional, Anderson, Larry D., additional, Milner, Carter, additional, Gasparetto, Cristina, additional, Agha, Mounzer, additional, Khan, Dr. Abdullah, additional, Hurd, David D, additional, Avigan, David E., additional, Costello, Caitlin, additional, Jakubowiak, Andrzej, additional, Lonial, Sagar, additional, Raje, Noopur S, additional, Medvedova, Eva, additional, McCarthy, Dr. Philip L., additional, Orlowski, Robert Z., additional, Nadeem, Omar, additional, Laubach, Jacob, additional, Pasquini, Marcelo, additional, Giralt, Sergio, additional, Masone, Kelly, additional, Samur, Mehmet, additional, Perrot, Aurore, additional, Moreau, Philippe, additional, Avet-Loiseau, Hervé, additional, Weller, Edie, additional, Munshi, Nikhil C., additional, and Anderson, Kenneth C., additional

Published
2023
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50. The role of ATG16L2 in autophagy and disease

Author

Laurence Luu, Natalia Castaño-Rodríguez, and Nadeem Omar Kaakoush

Subjects
Neoplasms, Autophagy, Humans, Autophagy-Related Proteins, Neurodegenerative Diseases, Cell Biology, Review, Inflammatory Bowel Diseases, Molecular Biology
Abstract

Macroautophagy/autophagy, a fundamental cell process for nutrient recycling and defense against pathogens (termed xenophagy), is crucial to human health. ATG16L2 (autophagy related 16 like 2) is an autophagic protein and a paralog of ATG16L1. Both proteins are implicated in similar diseases such as cancer and other chronic diseases; however, most autophagy studies to date have primarily focused on the function of ATG16L1, with ATG16L2 remaining uncharacterized and understudied. Overexpression of ATG16L2 has been reported in various cancers including colorectal, gastric, and prostate carcinomas, whereas altered methylation of ATG16L2 has been associated with lung cancer formation and poorer response to therapy in leukemia. In addition, ATG16L2 polymorphisms have been implicated in a range of other diseases including inflammatory bowel diseases and neurodegenerative disorders. Despite this likely role in human health, the function of this enigmatic protein in autophagy remains unknown. Here, we review current studies on ATG16L2 and collate evidence that suggests that this protein is a potential modulator of autophagy as well as the implications this has on pathogenesis. Abbreviations: ATG5: autophagy related 5; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; ATG16L2: autophagy related 16 like 2; CD: Crohn disease; IBD: inflammatory bowel diseases; IRGM: immunity related GTPase M; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PE: phosphatidylethanolamine; RB1CC1: RB1 inducible coiled-coil 1; SLE: systemic lupus erythematosus; WIPI2B: WD repeat domain, phosphoinositide interacting 2B

Published
2023

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