Browsing by Author "Kaufman, Howard L."

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    High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014
    (BMJ, 2014) Dutcher, Janice P.; Schwartzentruber, Douglas J.; Kaufman, Howard L.; Agarwala, Sanjiv S.; Tarhini, Ahmad A.; Lowder, James N.; Atkins, Michael B.; Surgery, School of Medicine
    Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as "cures". Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998. Electronic supplementary material The online version of this article (doi:10.1186/s40425-014-0026-0) contains supplementary material, which is available to authorized users.
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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.