Browsing by Author "Johnson, Douglas B."

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    Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group Part 2 TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors
    (Wolters Kluwer, 2017-11) Hendry, Shona; Salgado, Roberto; Gevaert, Thomas; Russell, Prudence A.; John, Tom; Thapa, Bibhusal; Christie, Michael; van de Vijver, Koen; Estrada, M. V.; Gonzalez-Ericsson, Paula I.; Sanders, Melinda; Solomon, Benjamin; Solinas, Cinzia; Van den Eynden, Gert G. G. M.; Allory, Yves; Preusser, Matthias; Hainfellner, Johannes; Pruneri, Giancarlo; Vingiani, Andrea; Demaria, Sandra; Symmans, Fraser; Nuciforo, Paolo; Comermo, Laura; Thompson, E. A.; Lakhani, Sunil; Kim, Seong-Rim; Schnitt, Stuart; Colpaert, Cecile; Sotiriou, Christos; Scherer, Stefan J.; Ignatiadis, Michail; Badve, Sunil S.; Pierce, Robert H.; Viale, Giuseppe; Sirtaine, Nicolas; Penault-Llorca, Frederique; Sugie, Tomohagu; Fineberg, Susan; Paik, Soonmyung; Srinivasan, Ashok; Richardson, Andrea; Wang, Yihong; Chmielik, Ewa; Brock, Jane; Johnson, Douglas B.; Balko, Justin; Wienert, Stephan; Bossuyt, Veerle; Michiels, Stefan; Ternes, Nils; Burchardi, Nicole; Luen, Stephen J.; Savas, Peter; Klauschen, Frederick; Watson, Peter H.; Nelson, Brad H.; Criscitiello, Carmen; O'Toole, Sandra; Larsimont, Denis; de Wind, Roland; Curigliano, Giuseppe; André, Fabrice; Lacroix-Triki, Magali; van de Vijver, Mark; Rojo, Federico; Floris, Giuseppe; Bedri, Shahinaz; Sparano, Joseph; Rimm, David; Nielsen, Torsten; Kos, Zuzana; Hewitt, Stephen; Singh, Baljit; Farshid, Gelareh; Loibl, Sibylle; Allison, Kimberly H.; Tung, Nadine; Adams, Sylvia; Willard-Gallo, Karen; Horlings, Hugo M.; Gandhi, Leena; Moreira, Andre; Hirsch, Fred; Dieci, Maria V.; Urbanowicz, Maria; Brcic, Iva; Korski, Konstanty; Gaire, Fabien; Koeppen, Hartmut; Lo, Amy; Giltnane, Jennifer; Rebelatto, Marlon C.; Steele, Keith E.; Zha, Jiping; Emancipator, Kenneth; Juco, Jonathan W.; Denkert, Carsten; Reis-Filho, Jorge; Loi, Sherene; Fox, Stephen B.; Pathology and Laboratory Medicine, School of Medicine
    Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
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    Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2
    (BMJ, 2021-02-04) Clark, Joseph I.; Curti, Brendan; Davis, Elizabeth J.; Kaufman, Howard; Amin, Asim; Alva, Ajjai; Logan, Theodore F.; Hauke, Ralph; Miletello, Gerald P.; Vaishampayan, Ulka; Johnson, Douglas B.; White, Richard L.; Wiernik, Peter H.; Dutcher, Janice P.; Medicine, School of Medicine
    High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.
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    Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium
    (American Society of Clinical Oncology, 2023) El Zarif, Talal; Nassar, Amin H.; Adib, Elio; Fitzgerald, Bailey G.; Huang, Jiaming; Mouhieddine, Tarek H.; Rubinstein, Paul G.; Nonato, Taylor; McKay, Rana R.; Li, Mingjia; Mittra, Arjun; Owen, Dwight H.; Baiocchi, Robert A.; Lorentsen, Michael; Dittus, Christopher; Dizman, Nazli; Falohun, Adewunmi; Abdel-Wahab, Noha; Diab, Adi; Bankapur, Anand; Reed, Alexandra; Kim, Chul; Arora, Aakriti; Shah, Neil J.; El-Am, Edward; Kozaily, Elie; Abdallah, Wassim; Al-Hader, Ahmad; Ghazal, Batool Abu; Saeed, Anwaar; Drolen, Claire; Lechner, Melissa G.; Drakaki, Alexandra; Baena, Javier; Nebhan, Caroline A.; Haykal, Tarek; Morse, Michael A.; Cortellini, Alessio; Pinato, David J.; Pria, Alessia Dalla; Hall, Evan; Bakalov, Veli; Bahary, Nathan; Rajkumar, Aarthi; Mangla, Ankit; Shah, Vishal; Singh, Parminder; Nana, Frank Aboubakar; Lopetegui-Lia, Nerea; Dima, Danai; Dobbs, Ryan W.; Funchain, Pauline; Saleem, Rabia; Woodford, Rachel; Long, Georgina V.; Menzies, Alexander M.; Genova, Carlo; Barletta, Giulia; Puri, Sonam; Florou, Vaia; Idossa, Dame; Saponara, Maristella; Queirolo, Paola; Lamberti, Giuseppe; Addeo, Alfredo; Bersanelli, Melissa; Freeman, Dory; Xie, Wanling; Reid, Erin G.; Chiao, Elizabeth Y.; Sharon, Elad; Johnson, Douglas B.; Ramaswami, Ramya; Bower, Mark; Emu, Brinda; Marron, Thomas U.; Choueiri, Toni K.; Baden, Lindsey R.; Lurain, Kathryn; Sonpavde, Guru P.; Naqash, Abdul Rafeh; Graduate Medical Education, School of Medicine
    Purpose: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. Methods: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). Results: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. Conclusion: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.
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    Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study
    (BMJ, 2025-03-03) Nassar, Amin H.; Abou Alaiwi, Sarah; El Zarif, Talal; Denu, Ryan; Macaron, Walid; Abdel-Wahab, Noha; Freeman, Dory; Vasbinder, Alexi; Hayeck, Salim; Anderson, Elizabeth; Goodman, Rachel S.; Johnson, Douglas B.; Grynberg, Shirly; Shapira, Ronnie; Kwan, Jennifer M.; Woodford, Rachel; Long, Georgina V.; Haykal, Tarek; Dent, Susan; Kojima, Yuki; Yonemor, Kan; Tandon, Ankita; Trevino, Alexandra; Akhter, Nausheen; Yang, Eric H.; Hui, Gavin; Drakaki, Alexandra; El-Am, Edward; Kozaily, Elie; Al-Hader, Ahmad; Farhat, Elias Bou; Babu, Priyanka; Mittra, Arjun; Li, Mingjia; Jones, Nicholas; Baena, Javier; Juarez Herrera, Mercedes; Foderaro, Simone; Aboubakar Nana, Frank; Kim, Chul; Sackstein, Paul; Parikh, Kaushal; Desai, Aakash P.; Smith, Caleb; Cortellini, Alessio; Pinato, David J.; Korolewicz, James; Lopetegui-Lia, Nerea; Funchain, Pauline; Choudhary, Arrush; Asnani, Aarti; Navani, Vishal; Meyers, Daniel; Stukalin, Igor; Ocejo Gallegos, Jesus Antonio; Trent, Jonathan; Nusrat, Sanober; Malvar, Carmel; McKay, Rana R.; Neilan, Tomas G.; Choueiri, Toni K.; Naqash, Abdul Rafeh; Medicine, School of Medicine
    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.