tbuckley/cabot-search huggingface dataset:
Germinal immunogenetics as a predictor of anti-PD1/PD-L1 treatment outcome.
Authors: Gerard A. Milano, Sadal Refae, Nathalie Ebran, Jocelyn Gal, Josiane Otto, Damien Drubay, Emmanuel Chamorey, Joseph Ciccolini, Esma Saada
Journal: Journal of Clinical Oncology (2018)

3034 Background: In the context of the checkpoint inhibitors (CPI) era and the strong demand for identification of predictive biomarkers, the role of the host must be considered. We developed a custom-designed panel of single nucleotide polymorphisms (SNPs) of relevant genes implicated in immune response. The prognostic value of this panel was explored in this study. Methods: Clinical data of advanced lung carcinoma patients treated by second-line anti-PD(L)1 in Centre Antoine Lacassagne (Nice, France) were collected. High-throughput genotyping of germinal DNA was performed by MassARRAY (AGENA Bioscience) using the custom-panel of 166 SNPs-86 selected genes (minor allelic frequency > 5% in a Caucasian population). Univariate and multivariate analyses for PFS were assessed, respectively, by means of log-rank tests and the Cox proportional hazards model. Multicollinearity was tested between all variables. P values ≤ 0.05 were considered statistically significant. Results: From October 2014 to April 2017, 48 patients were identified. Median age was 64-years-old; 29 were males (61%), 43 smokers (90%), 34 had radiotherapy (70%), 32 had adenocarcinoma (67%). Median follow-up was 12.5 months (95%CI: 11.0-16.3). All tested SNPs were in Hardy-Weinberg equilibrium. In univariate analyses, 25 individual SNPs significantly discriminated PFS. Multivariate analyses for PFS showed independent CPI prediction for ICOS rs11889031 (HR = 8.4 p < 0.001), TLR3 rs3775291 (HR = 4.9; p < 0.001), FAS rs1800682 (HR = 2.9; p = 0.03), FAS rs2234767 (HR = 4.8; p = 0.04), and INFL4 rs12979860 (HR = 4.3; p = 0.003). These genes and rs are closely involved in immunologic communication and auto immune disease. A composite score of favorable alleles (0-5) was dramatically associated with PFS (p < 0.001), median 2 months (95%CI: 0.6-2.3) for 0-1 (n = 7), median 8.3 months (95%CI: 0.3-13) for 2-3 (n = 29) and median-PFS not reached for 4-5 (n = 12). All SNPs concerned were located in intronic regions, according to https://www.ensembl.org., suggesting a variable impact on alternative splicing. Conclusions: This study points to the germinal immunogenetics as a significant piece in the CPI predictors puzzle.
TCT-400 Prevalence of Myocardial Bridging Associated with Coronary Endothelial Dysfunction in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease
Authors: Jaskanwal Deep Sara, Michel Corban, Megha Prasad, Abhiram Prasad, Lilach Lerman, Amir Lerman
Journal: Journal of the American College of Cardiology (2018)
Changes in quality of life at baseline, 6, and 12-months of the “Joven y Fuerte” prospective cohort pilot phase.
Authors: Cynthia Mayte Villarreal-Garza, Alejandra Platas, Melina Miaja, Alan Fonseca, Edna Anakarenn Lopez-Martinez, Bertha Alejandra Martinez-Cannon, Regina Barragan-Carrillo, Jose Felipe Muñoz-Lozano, Yoatzin Vega, Judy-Anne Williams Chapman, Itoro E Inoyo, Paul E. Goss, Enrique Bargallo-Rocha, Alejandro Mohar, Omar Peña-Curiel, Andrea Castro-Sanchez
Journal: Journal of Clinical Oncology (2018)

e18854 Background: Quality of life (QoL) has been reported to be lower in young women with breast cancer (YWBC). However, in limited resource settings with a high prevalence of YWBC, such as Mexico, the effects of diagnosis and treatment on QoL and their variation in time are largely unknown. We examined disease-related changes on QoL at baseline (BL), 6, and 12-months (m) of the “Joven y Fuerte” prospective cohort pilot phase. Methods: We prospectively accrued 96 YWBC (≤40 years) at two Mexican public cancer centers. Women completed QLQ-C30 and -BR23 surveys at BL and follow-up (FU). For analysis, we included non-metastatic and non-recurrent patients, that either completed BL and 6-m (n = 63) or 12-m (n = 48). We examined the changes in QoL from BL with matched t-tests. Results: Conclusions: Mexican YWBC experience significant deterioration in many QoL domains during first year FU, with a marked decrease at 6-m. Conversely, emotional functioning and future perspective improved over time. Our prospectively collected sociodemographic, clinical and pathological features data may elucidate these results to aid in developing tailored interventions for enhanced survivorship. BL 6-m p-value BL 12-m p-value QLQ-C30 Global score 72.22 69.71 NS 72.92 77.60 NS Physical functioning (fcn) 92.28 83.60 < .001 93.75 85.28 < .001 Role fcn 82.80 74.34 0.02 82.29 85.42 NS Emotional fcn 65.61 75.00 < .001 65.28 75.87 0.004 Cognitive fcn 83.86 76.19 0.01 81.60 79.17 NS Social fcn 76.98 71.43 NS 76.74 82.29 NS Fatigue 21.16 29.28 0.002 22.45 27.55 NS Nausea and vomiting 4.23 15.08 < .001 4.17 10.42 0.04 Pain 27.25 26.72 NS 24.31 21.18 NS Dyspnea 13.23 16.93 NS 16.67 10.42 NS Insomnia 25.40 30.16 NS 24.31 29.17 NS Appetite loss 10.58 11.64 NS 10.42 13.19 NS Constipation 15.87 22.22 NS 13.89 15.97 NS Diarrhea 6.88 9.52 NS 6.94 4.86 NS Financial difficulties 49.21 41.27 NS 48.61 44.44 NS QLQ-BR23 Body image 85.05 76.06 0.01 87.50 81.42 NS Sexual fcn 29.10 23.55 0.05 26.74 30.21 NS Sexual enjoyment 74.67 57.33 < .001 68.63 54.90 NS Future perspective 38.10 42.86 NS 37.50 56.25 < .001 Systemic therapy side effects 13.15 32.12 < .001 14.48 16.47 NS Breast symptoms 28.31 17.20 < .001 28.82 23.61 NS Arm symptoms 16.93 16.05 NS 18.06 17.59 NS Upset by hair loss 40.74 33.33 NS - - -
TCT-46 Mitral Valve Gradient, Heart Failure Admissions and One Year Mortality Following MitraClip Repair in 5,378 Patients: Results from the ACC/STS TVT Registry
Authors: Lowie Van Assche, Sreekanth Vemulapalli, James Thomas, Charles Davidson, Jyothy Puthumana, S. Malaisrie, Amanda Stebbins, Andrzej Kosinski, Jennifer Rymer, Ajay Jayant Kirtane, Vinod Thourani, Mark Ricciardi
Journal: Journal of the American College of Cardiology (2018)
Patterns of hepatitis B reactivation and liver test abnormalities in patients with chronic lymphocytic leukemia (CLL) treated with idelalisib plus an anti-CD20 antibody.
Authors: Andrew David Zelenetz, Anthony R. Mato, Tadeusz Robak, Jeffrey Alan Jones, John M. Pagel, Jacqueline Claudia Barrientos, Jennifer R. Brown, Marco Montillo, Thomas J. Kipps, Ronald Dubowy, Guan Xing, Julia Li, Peter Hillmen
Journal: Journal of Clinical Oncology (2016)

7533 Background: Hepatitis B reactivation can occur after hepatitis B virus (HBV) surface antigen (HBsAg) loss, especially in immunocompromised patients (pts).1,2A high rate of reactivation has been reported in such patients receiving an anti-CD20 antibody + chemotherapy. Incidence rates of HBV reactivation and transaminase elevation in CLL pts receiving idelalisib (IDELA) + anti-CD20 who are core antibody positive (anti-HBc+)/HBsAg−/HBV PCR− have not been reported. Methods: Data from 2 phase 3 clinical trials were analyzed to characterize the changes in liver tests and HBV reactivation (PCR− to PCR+). Eligible pts had relapsed/refractory (R/R) CLL treated with IDELA + rituximab (R), placebo + R, IDELA + ofatumumab (O), or O. Pts who were anti-HBc+/HBsAg− were only enrolled if they were HBV PCR−. Results: The analysis population of 477 pts included 390 anti-HBc−/HBsAg− and 85 anti-HBc+/HBsAg−/PCR− (missing data, n=2). Of those pts who were anti-HBc+, 3 had a history of HBV infection and 41 (IDELA + anti-CD20, n=22/45; anti-CD20, n=19/40) received IV immunoglobulin (IgG) for hypogammaglobulinemia before screening; 5 pts on IDELA + anti-CD20 and 3 on anti-CD20 received anti-HBV prophylaxis on-study. Patterns of changes in liver tests and HBV reactivationare shown in the table. Conclusions: Although false positive anti-HBc cannot be excluded in half of the patients due to IV IgG, no HBV reactivation was observed in pts receiving IDELA + anti-CD20. Prior exposure to HBV does not appear to be a risk factor for more frequent grade ≥3 liver test abnormalities. Clinical trial information: NCT01539512 and NCT01659021. IDELA + Anti-CD20 Anti-CD20 Anti-HBc+ (n=45) Anti-HBc− (n=238) Anti-HBc+ (n=40) Anti-HBc− (n=152) Grade ≥3 ALT/AST↑, n (%) 7 (15.6) 25 (10.5) 1 (2.5) 1 (0.7) P value 0.449 0.379 Median time to onset, wk 6.9 8.1 - - Grade ≥3 total bilirubin↑, n (%) 1 (2.2) 3 (1.3) 0 (0) 1 (0.7) Grade ≥3 gamma-glutamyl transferase↑, n (%) 1 (2.2) 13 (5.5) 3 (7.5) 1 (0.7) Drug discontinuation due to hepatic-related treatment-emergent adverse event, n (%) 0 (0) 8 (3.4) 0 (0) 0 (0) HBV reactivation, n 0 - 0 - References: 1.Hoofnagle JH. Hepatology. 2009;49(5 Suppl):S156-652.Mikulska M, et al. Clin Microbiol Infect. 2014;20:O694-701.
Correlation between baseline parameters and overall survival in patients with advanced melanoma treated with ipilimumab.
Authors: Marnix Heimen Geukes Foppen, Ekatarina S. Jordanova, Johannes V. Van Thienen, Simone Punt, Bart Van De Wiel, John B. A. G. Haanen, Christian U. Blank
Journal: Journal of Clinical Oncology (2017)

9572 Background: Checkpoint inhibitors (IT) have revolutionized treatment options for patients (pts) with advanced melanoma. Recently, we proposed a framework of 7 parameters (PM) describing requirements for a sufficient anti-tumor immune response (the “cancer immunogram”). In a first analysis we tested pts from our ipi cohort for outcome. Using this framework pts benefitting the most from treatment with ipi might be selected upfront, and in the future also from other checkpoint inhibitors. Methods: Using Kaplan-Meier- and Cox-regression-analysis correlations between 6 of these PM at baseline and overall survival (OS) were investigated in a single center cohort of pts treated with 3 mg/kg ipi for metastatic melanoma. Results of the 7 th PM are currently being finalized. Results: PM assessed were: LDH (≤ULN vs &gt; ULN), erythrocyte sedimentation rate (ESR,≤ULN vs &gt; ULN), absolute lymphocyte count (ALC, &lt; 1000/mm 3 vs ≥1000/mm 3 ) and IHC on tumor material for CD8+ T-cell infiltration ( &lt; median vs ≥median), PD-L1 expression ( &lt; 1% vs ≥1% positive cells) and MHC-class I expression (loss vs weak/positive). We analyzed 179 pts treated with ipi between 2010 and 2013. Median age was 55 years (19–88) and 61% of pts were male. Minimum follow-up of pts alive was 42 months(mo). Data were available as follows:177 cases LDH, 159 ALC/ESR, 118 PD-L1, 99 CD8 and 68 MHC-class I. Median OS was 7.1 mo. In univariable analysis LDH (HR 2.5, 95%CI 1.8-3.5), ALC (HR 1.6, 95%CI 1.1-2.4), ESR (HR 2.4, 95%CI 1.5-3.8) and CD8 (HR 1.8 95%CI 1.2-2.8) were significant for OS ( p&lt; 0.01). Pts with all 4 favorable PM had a median OS of 25.1mo(95%NR), pts with 3 PM 15.8 mo(95%CI 7.0-24.7), 2 PM 8.1 mo(95%CI 1.0-15.3), 1 PM 4.8 mo(95%CI 3.3-6.3) and no favorable PM 1.7 mo(95%CI 0–4.9). In multivariable analysis LDH(HR 2.4,95%CI 1.5-4.0) and CD8(HR 1.7,95%CI 1.1-2.8) were the only independent PM. Pts with a normal LDH and high CD8 had a median OS of 15.8 mo(95%CI 9.5-22.2) vs 3.8 mo(95%CI 1.8-5.7) for pts that did not ( p&lt; 0.01). Conclusions: In conclusion, low values of baseline LDH and high values of CD8 are the strongest PM associated with a favorable outcome in pts with advanced melanoma, treated with ipi. The other PM added low effect on the pts outcome upon ipi.
TRK wild-type and fusion protein expression in solid tumors: Characterization by immunohistochemistry and in situ hybridization
Authors: J. Feng, K. Ebata, F. Hansen, L. Kivi, C. Kriegshauser, D. Morosini, T.-S. Shen, A.N. Sireci, P. Thorne-Nuzzo, B. Tuch
Journal: Annals of Oncology (2018)

Background: Neurotrophic tyrosine receptor kinases (NTRK1-3) are a gene family encoding kinases involved in development and maturation of the central and peripheral nervous system. In cancer, fusion of one of these genes with various upstream partners leads to aberrant protein expression and unchecked proliferation. Identification of tumors driven by TRK fusions is clinically relevant because they can be targeted by highly selective small molecule inhibitors. Pan-TRK immunohistochemical (IHC) staining for aberrant expression of TRK proteins may be an important approach to identify tumors with TRK fusions when followed by confirmation.
Abstract 18876: Cardiomyocyte-Specific Deletion of TLR4 Attenuates Angiotensin II-Induced Hypertension and Improves Cardiac Function
Authors: Srinivas Sriramula, Yogesh Saini, Rohan Dharmakumar, Joseph Francis
Journal: Circulation (2016)

Toll-like receptor 4 (TLR4) plays an important role in inflammatory cardiovascular diseases including hypertension. We have previously showed that central TLR4 inhibition delayed progression of hyp...
The effect of post-operative chemotherapy and prognostic factors for colorectal cancer liver: Only metastasis (CRLM) after R0 or R1 resection.
Authors: Sun Jin Sym, Koen Kook Kim, Young Saing Kim, Inkeun Park, Won-Suk Lee, Jeong-Heum Baek, Yeon Ho Park, Hee Kyung Ahn, Eun Kyung Cho, Dongbok Shin
Journal: Journal of Clinical Oncology (2017)

e15047 Background:Complete removal of all known tumor is the most important indicator that correlated with survival of CRLM. However, the role of post-operative chemotherapy for resected CRLM has not yet been clarified. We evaluate the role of post-operative chemotherapy in setting for curatively resected CRLM. Methods:We reviewed all 164 patients (pts) underwent resection of CRLM in our institute between Nov 2002 and Apr 2016, and selected 109 pts underwent R0 or R1 resection of primary and CRLM. Pts with R2, extra-hepatic, and non-regional lymph nodes metastasis were excluded. Kaplan-Meier and log-rank test was used for survival analysis. Results:The median age was 62.9 (29-88) years; male (70%). Primary tumor locations were right (24.8%), left (52.3%), and rectum (22.9%). The median number and total sum of maximum diameter of CRLM were 2 (1-13) and 4.2 (0.6-19.7) cm, respectively. Eight-one pts (74%) underwent R0 resection of both primary tumor and CRLM and 84 pts (77%) received post-operative chemotherapy (66 pts with cytotoxic chemotherapy only, 18 with cytotoxic chemotherapy with biologics). With a median follow-up of 35.7 months, median overall survival was 57.0 months, and disease free survival (DFS) was 13.7 months. Univariate analysis revealed that node-stage of primary tumor ( p= 0.024), preoperative CEA (≤ 5 v &gt; 5 ng/ml)( p= 0.002), total sum of maximum diameter (≤ 5 v &gt; 5 cm)( p= 0.013), and complete resection of tumor (R0 v R1)( p&lt; 0.001) were significantly associated longer DFS. Post-operative chemotherapy did not show difference of DFS (median 7.5 months with no treatment, 14.2 months with cytotoxic chemotherapy, and 14.8 months with biologics, p= 0.739). In multivariate analysis, complete resection of tumor (Hazard Ratio (HR); 0.381, 95% confidence interval (CI); 0.215-0.646, p= 0.001) and preoperative CEA level (HR; 0.453, 95% CI; 1.015-3.621; p= 0.045) was independent factor for longer DFS. Conclusions: The post-operative chemotherapy for CRLM after R0 or R1 resection shows no difference in survival. Complete resection with negative surgical margin is the most important indicator for longer survival.
Molecular targeted therapies (MTT) in advanced chordoma (AC) patients (pts).
Authors: Loic Lebellec, Axel Le Cesne, Nicolas Penel, Jean-Yves Blay, Christine Chevreau, Emmanuelle Bompas, Francois Bertucci, Didier Cupissol, Michel Fabbro, Esma Saada, Florence Duffaud, Loic Feuvret, Alice Bonneville-Levard, Jacques-Olivier Bay, Elodie Vauleon, Georges Noel, Bruno Chauffert, Olivier Mir
Journal: Journal of Clinical Oncology (2016)

11020 Background: The data about the clinical benefit of MTT in AC pts are spare. Methods: Retrospective study of 74 AC pts treated between January 2004 and August 2015 in 12 major French sarcoma or neuro-oncology centers. Results: The sex ratio M/F was 42/32. The median age was 59 (12-86). The primary sites were sacrum (51, 69%), mobile spine (7, 9%) and skull base (16, 22%). Previous treatments were surgery (52, 70%), radiotherapy (36, 49%) and chemotherapy (10, 14%). Metastases present in 27 pts (37%) included lung (16, 22%), liver (4, 6%) and other sites (14, 19%). The 1st line of MTT consisted in imatinib (58, 78%), sorafenib (11, 15%), erlotinib (3, 4%), sunitinib and temsirolimus (1 each, 3%). The best objective response was PR (3, 4%: 2 with imatinib and 1 with sorafenib), SD (55, 74%), PD (9, 12%) and NE (7, 9%). Symptomatic improvement (SI) was seen in 23/61 assessable pts (38%) and was associated with SD/PR (p = 0.007). The PFS was 9 mo and the OS was 59 mo. In univariate analysis, the sole prognostic factor for PFS was prior radiotherapy (6 vs 14 mo, p = 0.031). Prognostic factor for OS were: age as continual variable (p = 0.001), WHO-PS (not reached, 47, 66, 4 respectively with 0, 1, 2 and 3, p = 0.026), primary location (sacrum 65 mo, mobile spine 49 mo and skull base 16 mo, p = 0.0001), pain requiring morphine (34 vs 65, p = 0.051), prior radiotherapy (30 vs 65 mo, p = 0.004), presence of liver met. (6 vs 59 mo, p = 0.015), presence of other met. (22 vs 59, p = 0.022) and anemia (34 vs 88, p = 0.043). The multivariate Cox model retained three independent prognostic factors: sacral primary location (HR = 0.22, p = 0.043), pain requiring morphine (HR = 3.6, p = 0.006) and liver met. (HR = 7.5, p = 0.002). 37 pts (50%) have received a 2nd line MTT, including imatinib (15, 41%), sorafenib (7, 19%) and erlotinib (6, 16%). The PFS was 5 mo; 2 PR (5%) were seen with erlotinib. SI with 2nd line (n = 7, 20%) was associated with SI in 1st line (p = 0.000037). SD/PR seen with 1st line were not predictive of SD/PR in 2nd line (p = 0.95). 18 pts have received 3rd line, including imatinib (3, 16%), sorafenib (8, 44%). The PFS was 2 mo; SI was seen in 5 pts (27%) and 1 pt (5%) receiving sorafenib experienced PR. Conclusions: Larger databases are needed to confirm the clinical benefit and validate clinical predictive factors.
Comprehensive molecular profiling of patients with pancreatic adenocarcinoma: A single institution’s experience.
Authors: Mandana Kamgar, Gregory Dyson, Maria Diab, Anteneh A. Tesfaye, W. Michael Korn, Anthony Frank Shields, Philip Agop Philip
Journal: Journal of Clinical Oncology (2018)

e16236 Background: Limited treatment options in patients with pancreatic adenocarcinoma (PDA) necessitate the search for new therapeutic targets. One area of major interest is the exploitation of DNA repair deficiencies. Methods: Tumors were examined using NextGen sequencing, immunohistochemistry, and in-situ hybridization. Tumor mutational load (TML) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated on known MSI loci in target regions. Copy Number Variation and gene fusion assessment was done in a subset of samples. Results: Tumors from 114 patients with PDA managed at Karmanos Cancer Institute were analyzed from 10/2014 to 2/ 2018.14 samples (12%, all needle biopsies) had insufficient tissue for intended analyses. Most frequent mutations were in KRAS (91%), p53 (66%), SMAD4 (25%), and p16 (15%). All samples but one were microsatellite stable. 12/39 samples had intermediate TML. PD-L1 expression was seen in 6/70 of samples. Pathologic mutations in select DNA repair genes were detected in 5 individuals (ATM = 2 BRCA1/2 = 3, PALB & POLE = 0). 2 of 3 patients with BRCA mutations had wild type KRAS, of those one was MSI-H. Potential druggable alterations were detected in 16 patients (PI3K = 3, PTEN = 2, CDKN2A = 6, NF1 = 1, CHEK2 = 1; ROS-1 fusion = 1, c-MET amplification = 1). There was no significant difference in the gene mutations based on disease stage. Expression of TOPO1, ERCC1 and TUBB3 was higher in metastatic samples. 2 of 3 patients with BRCA2 mutation had durable response to gemcitabine/nab-paclitaxel (Gem/nab-p) and Gem/cisplatin while the third with both BRAC1 and 2 mutations had rapid disease progression despite all therapies. One patient with ATM mutation has persistent response to Gem/nab-p for > 8 months, other one managed as local disease in 2013 and for metastasis to the lung in 2016 with radiation remains in remission. Conclusions: Comprehensive molecular profiling of PDA is feasible but the frequency of druggable molecular abnormalities is very low. DNA repair gene mutations were seen in ~5% of all tumors. Data suggest that BRCA and ATM mutated patients may also respond favorably to non-platinum based regimens.
Safety and activity of hydroxychloroquine and aldesleukin in metastatic renal cell carcinoma: A cytokine working group phase II study.
Authors: Leonard Joseph Appleman, Daniel Paul Normolle, Theodore F. Logan, Paul Monk, Thomas Olencki, David F. McDermott, Marc S. Ernstoff, Jodi Kathleen Maranchie, Rahul Atul Parikh, David Friedland, Herbert Zeh, Xiaoyan Liang, Lisa Helene Butterfield, Michael T. Lotze
Journal: Journal of Clinical Oncology (2018)

4573 Background: Aldesleukin (recombinant human interleukin-2, IL-2) has been an FDA-approved treatment for mRCC since 1992 with a 5-10% rate of durable complete response. Hydroxychloroquine (HCQ) inhibits cellular autophagy, a protective mechanism that enables cells to survive metabolic stress. In murine models, the combination of IL-2 and HCQ was associated with diminished toxicity and increased efficacy. We hypothesized that this combination would be tolerable and active in patients with metastatic renal cell carcinoma (mRCC). Methods: The Cytokine Working Group studied high-dose IL-2 in combination with oral HCQ for patients with mRCC. Subjects received IL-2, 600,000 International Units/kg, every 8 hours up to 14 doses/cycle. HCQ was administered daily by mouth, starting 2 weeks prior to the first dose of IL-2 and continued up to one year. The initial HCQ dose was 600 mg daily, with a planned dose escalation to 1200 mg daily. Subjects were monitored for safety and tolerability as well as response per RECIST 1.1. Results: 30 patients (9F, 22M) received study treatment, and 29 were evaluable for response. MSKCC prognostic group: good- 38%; intermediate- 55%; poor- 11%. Five subjects were treated at 600 mg daily HCQ with no unexpected toxicity. Thirteen subjects were then treated at HCQ 1200 mg. Of these, 2 experienced hypotension and tachycardia, and 1 patient died from pulmonary emboli. The cardiac events, consistent with IL-2 toxicity, were observed earlier in the course of treatment than anticipated. HCQ dose was therefore de-escalated to 600 mg daily, and 12 additional subjects were enrolled with no unexpected toxicity. There were 3 confirmed complete responses and 3 partial responses (1 confirmed); the median overall survival has not been reached. Surprisingly, median progression-free survival was 5 months for the 1200 mg cohort and > 17 months for the 600 mg group, 3-4x the historical duration. High baseline levels of serum hepatocyte growth factor > median predicted for inferior overall survival. Soluble LAG-3 levels increased with IL-2 therapy. Conclusions: IL-2 plus HCQ was well tolerated and clinically active with encouraging PFS of 17 months at the 600 mg HCQ dose. NCT01550367 Clinical trial information: NCT01550367.