Browsing by Author "Morse, Michael A."

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    Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry
    (BMC, 2017-12-19) Curti, Brendan; Daniels, Gregory A.; McDermott, David F.; Clark, Joseph I.; Kaufman, Howard L.; Logan, Theodore F.; Singh, Jatinder; Kaur, Meenu; Luna, Theresa L.; Gregory, Nancy; Morse, Michael A.; Wong, Michael K. K.; Dutcher, Janice P.; Medicine, School of Medicine
    Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the PROCLAIMSM registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all PROCLAIMSM patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response.
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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.