Denu, Ryan
Mayo Clinic
The University of Texas MD Anderson Cancer Center
Citations 2
Effectiveness and safety of immunotherapy in advanced NSCLC with pericardial effusions: a global retrospective multicenter study
Zarif, Talal El, Alaiwi, Sarah Abou, Gariazzo, Eleonora, Santo, Valentina, Garbo, Edoardo , Aldea, Mihaela, Pannu, Sagal, Semaan, Karl , Chehab, Omar , Hoballah, Malak, Y, Gao , Meyers, Daniel, Stukalin, Igor , Li, MT, Jones, Nicholas, Shapira, Ronnie, Vasbinder, Alexi, Hayek, Salim S. , Eid, Marc , Freeman, Dory, Parikh, Kaushal, Desai, Aakash, Cd, Smith, El-Am, Edward, Foderaro, Simone , Baena-, Javier, Cortellini, Alessio, Pinato, David J, Korolewicz, James , Kim, Chul , Sackstein, Paul, Denu, Ryan A, Abdel-wahab, Noha, Neilan, Tomas G. , Lima, Joao A C, Florez, Narjust, Janne, Pasi, Pecci, Federica , Choueiri, Toni K, Kwan, Jennifer M. , Naqash, Abdul Rafeh , Desai, Aakash , El Zarif, Talal , Garbo, Edoardo , Semaan, Karl , Grynberg, Shirly , Bou Farhat, Elias , Eid, Marc , Saad, Eddy , Desai, Aakash P , Kim, Chul , Jänne, Pasi A , Naqash, Abdul Rafeh , Hayek, Salim , Alaiwi, Sarah Abou , Nassar, Amin H. , Gariazzo, Eleonora , Santo, Valentina , Aldea, Mihaela , Paoloni, Francesco , Chehab, Omar , Navani, Vishal , Meyers, Daniel E. , Mittra, Arjun , Grynberg, Shirly , Vasbinder, Alexi L. , Farhat, Elias Bou , Saad, Eddy , Freeman, Dory , El‐Am, Edward , Nana, Frank Aboubakar , Baena, Javier, Herrera, Mercedes, Cortellini, Alessio , Pinato, David J. , Sackstein, Paul , Denu, Ryan , Macaron, Walid , Abdel‐Wahab, Noha , Lima, João A.C. , Florez, Narjust , Jänne, Pasi A. , Ricciuti, Biagio , Choueiri, Toni K.
The Oncologist | July 25, 2026 | Volume: 31 | Issue: 9 | Pages: No page available
Abstract Background There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.
Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study
Zarif, Talal El , Denu, Ryan , Abdel‐Wahab, Noha , Freeman, Dory , Hayeck, Salim, Anderson, Élizabeth , Goodman, Rachel , Johnson, Douglas B. , Grynberg, Shirly , Shapira, Ronnie, Kwan, Jennifer M. , Long, Georgina V. , Haykal, Tarek , Kojima, Yuki , Yonemor, Kan, Trevino, Alexandra , Hui, Gavin , Drakaki, Alexandra, El‐Am, Edward , Al‐Hader, Ahmad, Babu, P. Narendra , Li, Mingjia , Jones, N. , Herrera, M., Foderaro, Simone , Kim, Chul , Sackstein, Paul , Desai, Aakash , Smith, Caleb J. , Korolewicz, James , Lopetegui‐Lia, Nerea , Funchain, Pauline , Choudhary, Arrush, Asnani, Aarti , Stukalin, Igor , Gallegos, Jesús Antonio Ocejo , Nusrat, Sanober , Malvar, Carmel, McKay, Rana R. , Neilan, Tomas G. , Naqash, Abdul Rafeh , Baena, Javier , El Zarif, Talal , Goodman, Rachel S , Kim, Chul , Desai, Aakash P , Cortellini, Alessio , Pinato, David J , Navani, Vishal , Ocejo Gallegos, Jesus Antonio , Funchain, Pauline , Long, Georgina V , Naqash, Abdul Rafeh , Grynberg, Shirly , Espinar, Javier Baena , Alaiwi, Sarah Abou , Macaron, Walid , Vasbinder, Alexi L. , Woodford, Rachel , Dent, Susan , Kojima, Yuki, Tandon, Ankita, Akhter, Nausheen , Yang, Eric H. , Kozaily, Elie , Farhat, Elias Bou , Mittra, Arjun , Jones, Nicholas, Baena, Javier, Nana, Frank Aboubakar , Parikh, Kaushal , Cortellini, Alessio , Pinato, David J. , Meyers, Daniel E. , Trent, Jonathan C. , Choueiri, Toni K. , Korolewicz, James
Journal for ImmunoTherapy of Cancer | March 3, 2025 | Volume: 13 | Issue: 3 | Pages: e009364
Background Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results Among 110 pts, median age at ICI initiation was 65 (IQR: 59–75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. Conclusions Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.