Browsing by Author "Byrd, John C."

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    Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity
    (American Medical Association, 2023) Buck, Benjamin; Chum, Aaron P.; Patel, Mitkumar; Carter, Rebecca; Nawaz, Haseeb; Yildiz, Vedat; Ruz, Patrick; Wiczer, Tracy; Rogers, Kerry A.; Awan, Farrukh T.; Bhat, Seema; Guha, Avirup; Kittai, Adam S.; Simonetti, Orlando P.; Raman, Subha V.; Wallace, Grant; Sanchez, Reynaldo; Bonsu, Janice M.; Gambril, John; Haddad, Devin; Mann, James; Wei, Lai; Kola-Kehinde, Onaopepo; Byrd, John C.; Woyach, Jennifer A.; Addison, Daniel; Medicine, School of Medicine
    Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, setting, and participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main outcomes and measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.
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    In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs
    (Elsevier, 2015-08) Tefferi, Ayalew; Kantarjian, Hagop; Rajkumar, S. Vincent; Baker, Lawrence H.; Abkowitz, Jan L.; Adamson, John W.; Advani, Ranjana Hira; Allison, James; Antman, Karen H.; Bast Jr., Robert C.; Bennett, John M.; Benz Jr., Edward J.; Berliner, Nancy; Bertino, Joseph; Bhatia, Ravi; Bhatia, Smita; Bhojwani, Deepa; Blanke, Charles D.; Bloomfield, Clara D.; Bosserman, Linda; Broxmeyer, Hal E.; Byrd, John C.; Cabanillas, Fernando; Canellos, George Peter; Chabner, Bruce A.; Chanan-Khan, Asher; Cheson, Bruce; Clarkson, Bayard; Cohn, Susan L.; Colon-Otero, Gerardo; Cortese, Jorge; Coutre, Steven; Cristofanilli, Massimo; Curran Jr., Walter J.; Daley, George Q.; DeAngelo, Daniel J.; Deeg, H. Joachim; Einhorn, Lawrence H.; Erba, Harry P.; Esteva, Francisco J.; Estey, Elihu; Fidler, Isaiah J.; Foran, James; Forman, Stephen; Freireich, Emil; Fuchs, Charles; George, James N.; Gertz, Morie A.; Giralt, Sergio; Golomb, Harvey; Greenberg, Peter; Gutterman, Jordan; Handin, Robert I.; Hellman, Samuel; Hoff, Paulo Marcelo; Hoffman, Ronald; Hong, Waun Ki; Horowitz, Mary; Hortobagyi, Gabriel N.; Hudis, Clifford; Issa, Jean Pierre; Johnson, Bruce Evan; Kantoff, Philip W.; Kaushansky, Kenneth; Khayat, David; Khuri, Fadlo R.; Kipps, Thomas J.; Kripke, Margaret; Kyle, Robert A.; Larson, Richard A.; Lawrence, Theodore S.; Levine, Ross; Link, Michael P.; Lippman, Scott M.; Lonial, Sagar; Lyman, Gary H.; Markman, Maurie; Mendelsohn, John; Meropol, Neal J.; Messinger, Yoav; Mulvey, Therese M.; O’Brien, Susan; Perez-Soler, Roman; Pollock, Raphael; Prchal, Josef; Press, Oliver; Radich, Jerald; Rai, Kanti; Rosenberg, Saul A.; Rowe, Jacob M.; Rugo, Hope; Runowicz, Carolyn D.; Sandmaier, Brenda M.; Saven, Alan; Schafer, Andrew I.; Schiffer, Charles; Sekeres, Mikkael A.; Silver, Richard T.; Siu, Lillian L.; Steensma, David P.; Stewart, F. Marc; Stock, Wendy; Stone, Richard; Storb, Rainer; Strong, Louise C.; Tallman, Martin S.; Thompson, Michael; Ueno, Naoto T.; Van Etten, Richard A.; Vose, Julie M.; Wiernik, Peter H.; Winer, Eric P.; Younes, Anas; Zelenetz, Andrew D.; Department of Medicine, IU School of Medicine
    Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015]
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    A phase I trial of Flavopiridol in relapsed multiple myeloma
    (Springer, 2014-02) Hofmeister, Craig C.; Poi, Ming; Bowers, Mindy A.; Zhao, Weiqiang; Phelps, Mitch A.; Benson, Don M.; Kraut, Eric H.; Farag, Sherif; Efebera, Yvonne A.; Sexton, Jennifer; Lin, Thomas S.; Grever, Michael; Byrd, John C.; Department of Medicine, IU School of Medicine
    PURPOSE: Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. METHODS: Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus and then continuous infusion weekly for 4 weeks in a 6-week cycle. RESULTS: Fifteen patients were treated at three dose levels (30 mg/m(2) bolus, 30 mg/m(2) CIV to 50 mg/m(2) bolus, and 50 mg/m(2) CIV). Cytopenias were significant, and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients and grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein >50 % that did not persist. PK properties were similar to prior publications, and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. CONCLUSIONS: Flavopiridol as a single agent given by bolus and then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma