Citations 2
Major adverse cardiovascular events after teclistamab in relapsed refractory multiple myeloma: A multicenter study from the u.s. multiple myeloma immunotherapy consortium.
Zanwar, Saurabh , Goel, Utkarsh , Chao, Austin, Lien, Kyle, Mazzoni, Sandra , Khouri, Jack , Cassano, Raffaella Cassano , Addison, Daniel , Dominick, Anthony, Green, Kimberly M , Sborov, Douglas W. , Shetty, Sanath Kumar , Vazquez‐Martinez, Mariola , Avila, Gabriel De, Dixon, Ariel, Blue, Brandon , Freeman, Ciara L. , Ali, Hossam M. , Alomar, Mohammed , Alsina, Melissa , Shain, Kenneth H. , Davis, James A. , Davis, James A , Ali, Hossam M , Lee, Dae Hyun , Dima, Danai , Chao, Austin, Banerjee, Rahul , Williams, Louis S. , Anwer, Faiz , Lin, Yi , Cheng, Richard , Davis, James, Julian, Kelley , Shetty, Sanath, Locke, Frederick L. , Baz, Rachid , Puglianini, Omar Castañeda , Hansen, Doris K. , Grajales‐Cruz, Ariel , Raza, Shahzad
Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 4066-4066
Abstract Introduction: Teclistamab is the first FDA approved BCMA-directed bispecific antibody for the treatment of relapsed and refractory multiple myeloma (RRMM). With BCMA-targeting CAR-T therapies, cytokine release syndrome (CRS) is a risk factor for cardiotoxicity. Teclistamab was associated with fatal cardiovascular adverse events (CVAEs) in a recent US pharmacovigilance database analysis, but this analysis was limited by reporting bias. Therefore, the aim of our study is to conduct a multicenter study to define the real-world incidence of CVAEs in RRMM patients treated with teclistamab. Method We performed a retrospective multi-center cohort study of patients receiving teclistamab at 5 medical centers. Baseline oncologic and cardiovascular characteristics (including vital sign and echocardiographic data) were collected. Baseline cardiovascular disease (CVD) was defined as presence of coronary artery disease, congestive heart failure, severe or symptomatic valvular heart disease, or stroke at baseline. CVAE was collected and categorized based on CTCAE v5.0 by each institution. Major adverse cardiovascular event (MACE) was a composite outcome with any of the following: congestive heart failure, asymptomatic cardiomyopathy (interval LVEF drop >10% to resultant LVEF less than 50%), coronary artery disease requiring intervention, stroke or cardiovascular death. Arrhythmia was a composite outcome with any of the following: atrial tachyarrhythmia, ventricular tachyarrhythmia or bradyarrhythmia. Median follow-up was calculated through reverse Kaplan-Meier method. Multivariable Cox regression analysis was used to define the relation between MACE and survival. Cause of death was categorized as myeloma-related death or non-myeloma-related deaths (i.e. CRS, infection or cardiovascular death). Cause-specific Cox regression was performed to define relationship between MACE and cause of death. Results In a cohort of 219 patients treated with teclistamab with median follow-up of 20.1 months, 7.3% (N=16) developed MACE, 7.3% (N=16) developed arrhythmia and 12.8% (N=28) developing any MACE or arrhythmia. MACE occurred at a median of 4.5 days (IQR 2.25-15.75 days) after teclistamab step-up. The incidence of MACE was 16.4% in patients with baseline CVD versus 2.7% in those without baseline CVD (p<0.001). Patients who developed MACE had inferior ECOG performance status (PS) (PS >=2: 62.5% vs. 27.7%; p=0.008). Additionally, baseline hemoglobin level (9 vs 10g/dL; p=0.072) was numerically lower in MACE, compared to no MACE. There was no difference in age, sex, bone marrow (BM) plasma cell burden, ferritin, C-reactive protein or LDH levels between MACE vs. no MACE group. Patients who developed MACE had lower baseline diastolic blood pressure (67.7 vs 73.8mmHg; p=0.041) and numerically lower LVEF (51.4 vs 59.3%; p=0.059; baseline echocardiogram performed in 86% of all cohort). Patients who developed MACE had similar incidences of CRS (Grade >=2: 25.0 vs 16.7%; p=0.620) and immune effector cell-associated neurotoxicity (ICANS) grade 2 or higher (12.5 vs 7.5%; p=0.812). In multivariable Cox regression analysis, MACE was independently associated with inferior overall survival (HR 2.72; 95% CI 1.41-5.25; p=0.003), after adjusting for baseline CVD, age, high BM burden, extramedullary disease, and plasma cell leukemia. In cause-specific multivariable Cox regression analysis, MACE was independently associated with non-myeloma-related death (HR: 10.77 95% CI 4.39- 26.41; p<0.001) but not with myeloma-related death (1.54; 95% CI 0.64- 3.70; p=0.336). Conclusion In conclusion, in this large, real-world multicenter study, we observed that MACE occurred in over 7% of patients following teclistamab for RRMM, typically within 2 weeks of initiation. MACE was significantly associated with increased non-myeloma-related mortality. In contrast to CAR-T therapy, CRS or ICANS were not associated with MACE, whereas majority of patients who developed MACE had ECOG PS >=2 or baseline cardiovascular disease. More studies are necessary to define mechanisms and strategies to reduce these MACE and improve survival. Patients with baseline cardiovascular disease or poor performance status may benefit from cardiovascular optimization before and during teclistamab therapy.
Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19
Bakouny, Ziad , Grover, Punita , Hsu, Chih–Yuan , Alimohamed, Saif, Bilen, Mehmet Asım , Castellano, Cecilia A. , Desai, Aakash , Elkrief, Arielle , Eton, Omar , Fecher, Leslie A. , Flora, Daniel , Galsky, Matthew D. , Gesenhues, Alicia, Glover, Michael , Gopalakrishnan, Dharmesh , Gupta, Shilpa , Hayes‐Lattin, Brandon , Hendawi, Mohamed , Hsu, Emily , Jandarov, Roman , Jani, Chinmay , Johnson, Douglas B. , Khan, Hina, Khan, Shaheer , Koshkin, Vadim S. , Kulkarni, Amit , Kwon, Daniel H. , Matar, Sara , McKay, Rana R. , Mishra, Sanjay , Moria, Feras A., Nizam, Amanda , Nock, Nora L. , Nonato, Taylor K., Panasci, Justin , Pomerantz, Lauren , Portuguese, Andrew J. , Provenzano, Destie , Puc, Matthew , Rao, Yuan James , Rhodes, Terence D., Riely, Gregory J. , Ripp, Jacob , Rivera, Andrea Verghese, Shah, Sumit , Shaya, Justin , Subbiah, Suki , Tachiki, Lisa , Valdés-Reyes, Melissa , Weissmann, Lisa B., Wulff‐Burchfield, Elizabeth , Xie, Zhuoer , Yang, Yuanchu James , Shyr, Yu , Choueiri, Toni K. , Fromowitz, Ariel, Gandhi, Rikin, Gartrell, Benjamin A. , Makower, Della , Sullivan, Darciann O', Ohri, Nitin , Portes, Mary, Verma, Amit , Butt, Omar H. , Campian, Jian , Fiala, Mark A. , Monahan, Ryan, Bitran, Jacob D. , Hallmeyer, Sigrun , Mundt, Daniel , Pandravada, Sasirekha, Papaioannou, Philip V., Patel, Mauli, Streckfuss, Mitrianna, Tadesse, Eyob, Kundranda, Madappa N. , Lammers, Philip E. , Bindal, Poorva , Lam, Barbara C.C., Piper‐Vallillo, Andrew J., Arvanitis, Panos , Klein, Elizabeth J. , Vieira, Kendra, Angevine, Anne H., Bär, Michael, Prete, Salvatore A. Del , Fiebach, Maryann Z., Gulati, Anthony P., Hatton, Edward H., Houston, Kaly, Lo, K. M. Steve, Stratton, Jamie , Weinstein, Paul L., García, Jorge A. , Routy, Bertrand , Hoyo-Ulloa, Irma , Dawsey, Scott J. , Lemmon, Christopher A. , Sharifi, Nima , Granada, Carolina , Hoppenot, Claire , Connors, Jean M. , Demetri, George D., Freeman, Dory , Tolaney, Sara M. , Zon, Rebecca L. , Zhang, Tian , Dzimitrowicz, Hannah, Leighton, John, Grivas, Petros , Lynch, Ryan C. , Schweizer, Michael T. , Vinayak, Shaveta , Wagner, Michael J. , Dansoa, Yvonne , Manikowski, Jesse, Vadakara, Joseph , Yossef, Kristena, Beckerman, Jennifer, Goyal, Sharad , Messing, Ian , Steffes, Dawn R., Alsamarai, Susan, Clément, Jessica , Cosin, Jonathan A. , Daher, Ahmad , Dailey, Mark E., Hosmer, Wylie, Jayaraj, Asha, Mather, Jeff, Menendez, Alvaro G. , Nadkarni, Rajani, Serrano, Oscar K. , Yu, Peter Paul , Balanchivadze, Nino, Accordino, Melissa , Bodin, Brianne E, Masson, Cynthia, Alexander, Mariam P., Mushtaq, Sarah, Bernicker, Eric , Deeken, John F. , Jeffords, Kelly J., Shafer, Danielle , Cárdenas, Ana I, Campos, Rogelio Cuervo, Ramirez, Ana, Gill, David , Lewis, Mark A. , Low, Clarke A., Jones, Michelle M, Mansoor, Abdul-Hai, Mashru, Sandeep H., Werner, Mica A., Cohen, Aaron , Nemecek, Eneida R. , Williamson, Staci, Smith, Stephanie J., Lewis, Grant C., Zaren, Howard A. , Akhtari, Mojtaba, Castillo, Dan R., Cortez, Kimberly, Lau, Eric , Park, Kyu, Reeves, Mark E. , O’Connor, Timothy E. , Altman, Jessica K. , Gurley, Michael, Mulcahy, Mary F. , Ramesh, Vidhyalakshmi , Sachs, Zohar , Wilson, Grace, Bardia, Aditya , Gainor, Justin F. , Peppercorn, Jeffrey , Reynolds, Kerry L. , Zubiri, Leyre , Riaz, Irbaz B, Shah, Surbhi, Ayre, Susan K., Bonnen, Mark , Mahadevan, Daruka , McKeown, Cindy, Salazar, Mary, Wang, Chen‐Pin , Bouganim, Nathaniel , Sabbah, Arielle , Tagalakis, Vicky , Nanchal, Rahul , Bahadur, Nadia , Belenkaya, Rimma , Nambiar, Puja H. , Papadopoulos, Esperanza B. , Rosenberg, Jonathan E, Cerrone, Kim, Dill, Jennifer A. , Faller, Bryan A. , Alomar, Mohammed , Hume, Emma C, Islam, Jessica Y. , Ajmera, Archana , Brouha, Sharon S. , Choi, Sharon , Jiang, Jun Yang , Kligerman, Seth , Park, Ji, Bhatt, Padmanabh , Mariano, Melissa G., Thomson, Carey C. , Glace, Mary Grace, Knoble, Jeanna, Zacks, Rosemary, Blau, Sibel , Brown, CarrieAnn, Cantrell, Angela Shaw, Namburi, Swathi, Polimera, Hyma , Rovito, Marc A., Edwin, Natasha, Herz, Katrina, Kennecke, Hagen F. , Monfared, Amelia, Sautter, Rachel R, Cronin, Tara, Elshoury, Amro, Fleissner, Bridget, Hernandez‐Ilizaliturri, Francisco J. , Kariapper, Ariffa, Levine, Ellis , Wicher, Camille P., Misdary, Christian, Shah, Mansi , Batist, Gerald , Cook, Erin , Ferrario, Cristiano , Lau, Susie , Rudski, Lawrence , Dutra, Míriam Santos , Mahmood, Sana , Mico, Vasil, Dixon, Becky, Logan, Barbara, Mandapakala, Chaitanya, Cabebe, Elwyn C., Jha, Alokkumar , Schapira, Lidia , Lopes, Gilberto , Cardenas, Karen de, Russell, Karen , Stith, Brittany, Taylor, Sharona, Klamerus, Justin F., Revankar, Sanjay G. , Addison, Daniel , Chen, James L. , Haynam, Marcy , Jhawar, Sachin R, Karivedu, Vidhya , Pillainayagam, Clement, Wall, Sarah , Williams, Nicole , Abbasi, Saqib Hussen, Annis, Sandy, Balmaceda, Nicole , Greenland, Steven, Kasi, Anup , Rock, Crosby D. , Luders, Matt, Smits, Melissa, Weiss, Matthias , Chism, David D. , Owenby, Susie, Ang, Celina , Doroshow, Deborah B. , Metzger, Megan , Uyehara, Catherine, Lashley, Latoya N., Sueyoshi, Mark, Patel, Kanishka G. , Riess, Jonathan W. , Borno, Hala T. , Rubinstein, Samuel M. , Ahmad, Syed A. , Brownfield, Lauren, Heilman, Hannah, Kharofa, Jordan , Marcum, Michelle, Sohal, Davendra , Geiger, Christopher L., Russ, Atlantis Dawn, Saker, Haneen , Choi, Horyun, Rho, Young Soo , Feldman, Lawrence , Gantt, Gerald, Hoskins, Kent , Khan, Mahir, Liu, Li , Nguyen, Ryan H, Schwartz, Candice, Venepalli, Neeta K. , Boldt, Anne, Gonzalez, Cyndi J, Su, Chris, Yoon, James J., Bijjula, Ragneel R., Mavromatis, Blanche H., Seletyn, Mildred E., Wood, Barbara R., Kaklamani, Virginia , Beeghly, Alicia, Charles, Lawrence J., Cheng, Alex , Ding, Tan, Enriquez, Kyle T. , French, Benjamin , Gillaspie, Erin A. , Hennessy, Cassandra , Lewis, Judy T., Reid, Sonya , Saif, Sara, Slosky, David, Solórzano, Carmen C. , Sun, Tianyi , Vega-Luna, Karen, Carducci, Theresa M., Goldsmith, Karen J., Loon, Susan Van, Topaloĝlu, Ümit , Moore, Joan K., Rice, Robert, Cabalona, Wilhelmina D., Cyr, Sandra, McCollough, Briana Barrow, Peddi, Prakash , Rosen, L, Ravindranathan, Deepak , LoRusso, Patricia , Lustberg, Maryam B. , Masters, Tyler, Verma, Amit , Sachs, Zohar , Choueiri, Toni K , Desai, Aakash P , Bakouny, Ziad , Mishra, Sanjay , Xie, Zhuoer , Zubiri, Leyre , Fiala, Mark A , Bilen, Mehmet A , Portuguese, Andrew J , Lustberg, Maryam , Labaki, Chris , Awosika, Joy A. , Gulati, Shuchi , Bashir, Babar , Berg, Stephanie , Bowles, Daniel W. , Gatti-Mays, Margaret Elena , Hálfdánarson, Þorvarður R. , Hendawi, Mohamed, Hwang, Clara , Joshi, Monika , Knox, Natalie, Ruíz‐García, Erika , Schmidt, Andrew , Schoenfeld, Adam Jacob , Schwartz, Gary K. , Tucker, Matthew D. , Wotman, Michael T. , Thompson, Michael A. , Shah, Dimpy P. , Warner, Jeremy L. , Wise-Draper, Trisha Michel , Goel, Sanjay , Halmos, Balázs , Shapiro, Lauren C. , Shastri, Aditi , Sica, Roberto Alejandro , Henderson, Jeffrey P. , Stockerl‐Goldstein, Keith , Zhou, Alice Y. , Tadesse, Eyob, Gatson, Na Tosha , Loree, Jonathan M. , Lam, Barbara, Peters, Mary Linton B , Egan, Pamela , Farmakiotis, Dimitrios , Olszewski, Adam J. , Hatton, Edward, Rose, Suzanne J. , Pennell, Nathan A , Painter, Corrie , Li, Ang , Bitterman, Danielle S. , Florez, Narjust , Giordano, Antonio , Morgans, Alicia K. , Nohria, Anju , Saliby, Renée Maria , Van Allen, Eliezer M , Xu, Wenxin Vincent , Halabi, Susan , Graber, Jerome J. , Hawley, Jessica E. , Loggers, Elizabeth T , Lyman, Gary H , Nakasone, Elizabeth S. , Yeh, Albert C. , Makary, Mina S. , Rosenstein, Lori J. , Elias, Rawad , Fein, Joshua Alexander , Gadgeel, Shirish M. , Bhutani, Divaya , Hershman, Dawn L. , Alexander, Mariam, Reuben, Daniel Y. , De‐la‐Rosa‐Martinez, Daniel , Vilar‐Compte, Diana , McWeeney, Shannon K. , Peters, Solange , Nagaraj, Gayathri , Wehbe, Firas , Durbin, Eric B. , Nelson, Heather H. , Boland, Genevieve M. , Rosovsky, Rachel , Bekaii‐Saab, Tanios , Joyner, Michael J. , Senefeld, Jonathon W. , Mesa, Ruben A. , Ramirez, Amelie G , Shah, Pankil , Papenburg, Jesse , Vinh, Donald Cuong , Singh, Harpreet , Bao, Ting , O'Cearbhaill, Roisin E , Philip, John , Robson, Mark E. , Rosenberg, Jonathan E, Wilkins, Cy R. , Tamimi, Rulla M. , Dill, Jennifer, Chandrasekhar, Sanjay Amrith , Cabal, Angelo , Hsiao, Albert , Razavi, Pedram , Reid, Erin G , Rink, Cameron L. , Griffiths, Elizabeth A. , Jain, Prantesh , Moffitt, Melissa , O’Connor, Tracey L. , Smith, Laurie J, Zsíros, Emese , Jabbour, Salma K , Cook, Erin, Miller, Wilson H. , Wilchesky, Machelle , McNair, Christopher M. , Kloecker, Goetz Hans , Khaki, Ali Raza , Nagpal, Seema , Wu, Julie , Whaley, David, Jhawar, Sachin R, Palmer, Joshua D. , Stover, Daniel G. , Berenberg, Jeffrey L. , Fazio, Alyson, Huber, Kathryn E. , Small, Eric J. , Zhang, Sylvia , Andermann, Tessa M. , Jensen, Christopher Edward , Wood, William A. , Latif, Tahir , Shaikh, Hira , Abidi, Maheen Z. , Markham, Merry Jennifer , Acoba, Jared David , Nguyen, Ryan H, Pasquinelli, Mary M. , Vikas, Praveen , Zakharia, Yousef , Friese, Christopher R. , Su, Christopher , Zaman, Qamar U, Brown, Alaina J. , Crispens, Marta Ann , Croessmann, Sarah , Davis, Elizabeth J. , Duda, Stephany N. , Hausrath, Daniel J. , Li, Xuanyi , Prescott, Lauren Shore , Wang, Lucy Lu , Aboulafia, David M. , Hafez, Navid , Herbst, Roy S. , Stratton, Catherine
JAMA Oncology | November 3, 2022 | Volume: 9 | Issue: 1 | Pages: 128
ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701