bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency of BCR-ABL oncogene in pediatric acute lymphoblastic leukemia (ALL) patients as revealed by RT-PCR and interphase FISH: Association with disease biology and treatment outcome.
Authors: Iqbal Zafar , Awan Tashfin , Iqbal Mudassar , Sabir Noreen , Asad Sultan , Siddique Mohammad Hasan , Sahar Sumrin , Tahir Ammara H , Aleem Aamer , Akhtar Tanveer ,   H.O.P.E.S. Group
Published: March 2020

6612 Background: ALL is a complex genetic disease involving many fusion oncogenes (FGs)1 frequency of which can vary in different ethnic groups2,3 thus having implication in differential diagnosis, prognosis and treatment. Methods: We studied FGs in 101 pediatric ALL patients using RT-PCR1 at Day 0, Day 15 and Day 29 and Interphase FISH, and their association with clinical features and treatment outcome. Results: Five most common FGs i.e. BCRABL (t 22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 88.1% (89/101) patients. Frequency of BCR-ABL was 44.5% (45/101). Patients with BCR-ABL had significantly lower survival (43.733 weeks ±4.241) as compared to others except MLL-AF4 and significantly higher TLC count. Overall survival was lower (52.2±3.75) than the patients with ETV6-RUN X 1 (65.2± 9.9) which may be due to overall high frequency of poor prognostic FGs (71%) as compared to ETV6-RUNX 1 (17.1%) (p=0.01). Conclusions: This is the first study from Pakistan correlating molecular markers, disease biology and treatment response. It is the highest reported frequency of BCR-ABL in pediatric ALL and was associated with disease biology and survival. Some authors have reported BCR-ABL frequency higher than in West2,4,5 while others reported 45% frequency of ETV6-RUNX16. These and our data reflect strong interplay of genetic and environmental factors in biology of pediatric ALL and its correlation with disease biology and treatment2,3. Our data indicates immediate need for large clinical trials of imatinib, dasatinib and nilotinib in paediatric ALL treatment in our ethnic group. This study will lead to unravel the mechanisms of BCR-ABL Leukemogenesis and to find population-specific biomarkers and drug targets. References: 1) van Dongen JJ, et al., Leukemia. 1999 Dec; 13(12):1901-28. 2) Iqbal Z, et al. J Pediatr Hematol Oncol. 2007 Aug; 29(8):585. 3) Ariffin H, et al. J Pediatr Hematol Oncol. 2007 Jan; 29(1):27-31. 4) Ramos C, et al. 2011 Sep; 139(9):1135-42. 5) Artigas A CG, et al. Rev Med Chil. 2006 Nov; 134(11):1367-76. 6) Karrman K, et al. Br J Haematol. 2006 Nov; 135(3):352-4.
Epigenetically induced expression of CD30 in T-PLL: A rationale for the use of brentuximab vedotin.
Authors: Hasanali Zainul , Sharma Kamal , Shimko Sara , Stuart August , Liu Xin , Epner Elliot E , Loughran Thomas P. 
Published: March 2020

6616 Background: T-cell prolymphocytic leukemia (T-PLL) is characterized by high lymphocyte counts, skin involvement and enlarged organs. Treatment with alemtuzumab (alem) induces complete remission (CR) in >50% of patients, duration is short (median: 6 mos). Therapy with the histone deacetylase inhibitors (HDACi) vorinostat (SAHA) or romidepsin (romi) and cladribine (2-CdA), may augment mAb activity. Methods: Five T-PLL patients were studied (Table). Diagnosis was made by pathology, flow cytometry and TCR studies. Alem (30 mg sq d1,3,5) and 2-CdA (5mg/m2 d1-5), followed by alem, 2-CdA and SAHA (400mg q d X 5 days) or romi (14mg/m2d 1,8,15) was given. One patient with skin lesions expressed CD30 and received brentuximab vedotin (SGN-35). Results: All patients achieved CR (mean: 10; median: 8 mos). Relapsed patients responded with repeat dosing. Genes assayed indicate involvement of the MAPK pathway (p53, DUSP2, TRIB1, C/EBP). mRNA expression of the membrane receptor CD30 (TNFRSF8) increased following therapy in 4/5 patients (mean: 14; Range: 1.3-69 fold). CD30 protein was confirmed by IHC and Western blotting. One patient with relapsed T-PLL involving skin had a dramatic clearing of lesions and blood counts after one dose of SGN35. Conclusions: Therapy with HDACi and 2-CdA overcomes resistance and augments clinical activity of alem and SGN-35, as evidenced by derepression of CD30 and response to treatment. We present a rationale for epigenetic resensitization to mAbs and their drug conjugates (ADC) in T-PLL. A prospective multicenter clinical trial is warranted. [Table: see text]
Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
Authors: Amrein Philip C. , Attar Eyal C. , Fathi Amir Tahmasb , McAfee Steven L , Wadleigh Martha , DeAngelo Daniel J. , Steensma David P. , Foster Julia , Stone Richard M. , Neuberg Donna S. , Ballen Karen K. ,   Massachusetts General Hospital/Dana-Farber Cancer Institute/Harvard Cancer Center
Published: March 2020

6621 Background: Both bortezomib (Bz) and lenalidomide have clinical activity in patients with MDS and AML. We conducted a phase I dose escalation study to determine the maximal tolerated dose (MTD) of Bz in combination with lenalidomide. Methods: Patients with MDS (IPSS score ≥ 0.5 or therapy-related) received Bz by IV bolus on Days 1, 4, 8, and 11 and lenalidomide 10 mg/day PO on Days 1-21 in 28 day cycles for up to 9 cycles. Three doses of Bz were tested (0.7, 1.0, or 1.3 mg/m2). Cohorts consisted of 3-6 patients; the dose of Bz was escalated if there were < 2 dose limiting toxicities (DLTs). Growth factor support and transfusions were permitted. Dose limiting toxicities (DLTs) were assessed during the first cycle and were defined as severe neutropenia (absolute neutrophil count ≤ 250/ul), thrombocytopenia (platelet count < 10,000/ul), grade ≥ 2 neurotoxicity, or other grade ≥ 3 non-hematologic toxicity. Following determination of the MTD, enrollment opened to patients with relapsed and refractory AML and those with untreated high risk disease for whom induction therapy was not indicated. Responses were assessed by IWG 2006 criteria for MDS and IWG 2003 criteria for AML. Results: 23 patients (14 men) were enrolled; one patient was inevaluable due to disease progression prior to starting protocol therapy. The median age was 73 years (range 54-87). There was 1 DLT observed, neutropenia, in 6 patients treated with 1.0 mg/m2 Bz and no DLTs at 0.7 or 1.3 mg/m2. The median number of cycles was 2 (range 2-9). Grade ≥ 3 toxicities possibly attributable to the treatment at any dose level were: anemia (2), thrombocytopenia (10), leukopenia (3), infection (1), rash (2), dyspnea (1), dizziness (1), hypotension (1), pneumonia (2) and neuropathy (1). Among the 14 patients with MDS, 1 patient with RARS experienced a CR and 2 with RAEB-2 experienced marrow CR (mCR). Among the 8 patients with AML, there was 1 CR. Conclusions: The maximal tested dose of Bz (1.3 mg/m2) in combination with lenalidomide is safe. Responses were seen in MDS and high risk AML. Future testing of this regimen is planned.
Regional variation in treatment costs and survival for elderly patients with myelodysplastic syndromes.
Authors: Ma Xiaomei , Wang Rong , Long Jessica B. , Gold Heather Taffet , Halene Stephanie , Gross Cary P. 
Published: March 2020

6628 Background: Myelodysplastic syndromes (MDS) occur primarily in the elderly (≥65 years). The expected 5-year cost for an elderly MDS patient tops $63,200 in 2009 US$. This study assessed regional variation in the cost of care and survival for elderly MDS patients. Methods: Using the Surveillance Epidemiology and End Results–Medicare data, we identified primary MDS patients aged 66-99 years diagnosed from 2001-2007, had continuous fee-for-service coverage for Parts A and B, and had no history of other cancer. We assigned patients to Dartmouth Atlas of Health Care Hospital Referral Regions (HRRs) based on their residence at time of diagnosis. We also selected controls from a 5% sample of Medicare beneficiaries without cancer and matched controls 1:1 to patients by HRR, age, sex, pre-diagnosis cost and comorbidity. All Medicare claims through 2009 were tallied, and MDS-related costs were defined as the difference between the payments for a patient and a matched control. Results: With 6244 patients in 73 HRRs, the average 3-year MDS-related cost varied across HRRs, ranging from $12,900 to $83,600 (2009 US$). Patients in high-spending regions had more comorbidities and higher Medicare costs before diagnosis and were more likely to be racial minorities and live in lower-income areas. Three-year survival ranged from 13.0% to 62.1%. However, there was no significant correlation between 3-year costs and 3-year survival (ρ=-0.06, p=0.61). The hazard ratios (HR) for higher spending regions compared to the lowest-expenditure region were near 1, after controlling for covariates including MDS subtype (2nd quartile: HR=1.03, 95% CI: 0.94-1.12; 2nd quartile: HR=1.04, 95% CI: 0.95-1.14; 4th quartile: HR=0.98, 95% CI: 0.90-1.08). Conclusions: We observed considerable regional variation in Medicare expenditure on elderly MDS patients during the first 3 years post-diagnosis. However, patients in higher cost regions had similar 3-year survival to patients in lower cost regions. Given the substantial economic burden of MDS and Medicare’s current fiscal challenges, it is important to further assess the factors associated with higher regional costs and to improve the care of MDS patients in a cost-efficient way.
Phase II study of pemetrexed (P) plus carboplatin (Cb) or cisplatin (C) with concurrent radiation therapy followed by pemetrexed consolidation in patients (pts) with favorable-prognosis inoperable stage IIIA/B non-small cell lung cancer (NSCLC).
Authors: Choy Hak , Schwartzberg Lee Steven , Dakhil Shaker R. , Garon Edward B. , Choksi Janak K. , Govindan Ramaswamy , Peng Guangbin , Koustenis Andrew , Treat Joseph , Obasaju Coleman K. 
Published: March 2020

7002 Background: There is no consensus chemotherapy regimen with concurrent radiation therapy (CRT) for inoperable stage IIIA/B NSCLC. P synergizes with ionizing radiation, as well as with Cb and C in preclinical models. These doublets have shown efficacy and favorable toxicity profiles in phase II/III trials. Methods: In this open-label randomized phase II trial, 98pts with inoperable stage IIIA/B NSCLC (all histologies) were randomized (1:1) to P 500 mg/m2 plus Cb AUC 5 (PCb) or P 500 mg/m2 plus C 75 mg/m2 (PC) intravenously (IV) every 21 days for 3 cycles. All pts received CRT 64–68 Gy (2 Gy/day, 5 days/week, Days 1–45). Consolidation P 500 mg/m2 IV every 21 days for 3 cycles began 3 weeks after completion of CRT. The primary endpoint was 2-year overall survival (OS); secondary endpoints included median OS, time to progression (TTP), overall response rate (ORR), and toxicity. Results: Since Jun 2007, 98 pts were enrolled (PCb: 46; PC: 52).Pts were followed until Oct 2011. Mean dose compliance was PCb: 95.7% P, 97.1% Cb; PC: 89.7% P, 89.1% C. Mean dose compliance for CRT was PCb: 95.7%; PC: 88.1%. CRT dose interruptions occurred in PCb: 32.6% and PC: 40.4%. Two-year OS was PCb: 45.2% (95% confidence interval [CI], 29.3-59.8); PC: 57.6% (95% CI, 41.6-70.7); p=0.270. Median OS (months) was PCb: 18.7 (95% CI, 12.9-not assessable [N/A]); PC: 27.0 (95% CI, 23.2-N/A). Median TTP (months) was PCb: 8.8 (95% CI, 6.0-10.7); PC: 13.1 (95% CI, 8.3-N/A); p=0.057. The ORR rates were PCb: 52.2% (complete response [CR], 6.5%; partial response [PR], 45.7%); PC: 46.2% (CR, 3.8%; PR, 42.3%). Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. No drug-related deaths were reported. Conclusions: While conclusions are limited by the size of the trial, this study suggests OS and TTP advantages for the C-containing arm. Both combinations with CRT appear well tolerated.
Quantitating pathologic response to neoadjuvant chemotherapy in KRAS-mutated versus nonmutated lung cancers.
Authors: Chaft Jamie E. , Paik Paul K. , Sima Camelia S. , Kris Mark G. , Krug Lee M. , Azzoli Christopher G. , Riely Gregory J. , Pietanza Maria Catherine , Rusch Valerie W. , Travis William D , Rizvi Naiyer A. 
Published: March 2020

7014 Background: Trials of neoadjuvant chemotherapy in non-small cell lung cancers (NSCLC) have demonstrated that pathologic response correlates with downstaging and survival. There is controversy as to whether KRAS mutated patients (pts) have the same benefit with adjuvant chemotherapy as non-mutated pts however the impact of KRAS mutations on response to neoadjuvant therapy has not been reported. Methods: Pts with resectable stage I-III non-squamous NSCLCs were treated with 4 cycles of cisplatin, docetaxel, and bevacizumab, followed by surgical resection. Tumors were tested for KRAS mutations. Percent treatment effect (necrosis, inflammation, fibrosis) was quantified histologically. Pts were followed until disease recurrence and/or death. Binary variables were compared using the Fisher’s Exact Test. Survival was assessed by pathological response based on the literature (≥90 vs <90%) using the Kaplan-Meier method, stratified by stage (IB-IIB vs. III) and by KRAS mutation. Results: We accrued 51 pts. 34/51 (67%) had clinical stage IIIA disease. 48 had molecular testing: 14/48 (29%) had KRAS mutations and 4/48 (8%) had EGFR mutations. The median follow-up was 2 years (yr) (range, 3-63 months). 41 pts had resection and analysis for pathological response. The 2 yr disease free survival (DFS) and overall survival (OS) were superior in the 11/41 (27%) with ≥90% versus those with <90% treatment effect: DFS 91% vs. 56%, p=0.029 and OS 100% vs. 60%, p=0.013. These outcomes remained significant when adjusted for stage. For pts with KRAS mutations, 0 of 10 tumors analyzed had ≥90% treatment effect whereas 11 of 31 (35%) pts with wild-type KRAS had ≥90%, p=0.039. There was an inferior median OS for KRAS mutated pts (22 months) compared to pts without a known KRAS mutation, (Not Reached, p=0.03). Conclusions: Following neoadjuvant chemotherapy, pts with tumors having ≥90% necrosis had improved survival. There were no patients with KRAS mutation that achieved ≥90% treatment effect in response to cisplatin, docetaxel, and bevacizumab. Adaptive adjuvant trial strategies to improve upon outcomes of those with <90% necrosis at resection and new approaches specifically targeting KRAS-mutated NSCLCs are needed.
Prognostic impact of the number of examined lymph nodes (LNs) in resected node negative (pNo) non-small cell lung cancer (NSCLC).
Authors: Ogbata Obiageli Uchenna , Yu Xinhua , Osarogiagbon Raymond U 
Published: March 2020

7025 Background: In the US, 29% of patients undergo curative-intent surgery for NSCLC. Absence of LN metastasis and the extent of LN examination influence survival. 44% of patients with pathological node negative (pN0) disease die within 5 years. There is no consensus on the optimal number of LNs to be examined to determine pN0 stage. We hypothesized that patients with few examined nodes may have missed nodal metastasis and increasing the number of LNs examined would improve survival. Methods: Retrospective SEER database analysis of NSCLC resections from 1998 to 2002, with survival updated to 2008. Patients with first primary, pN0 NSCLC, with one or more LNs examined, met our study criteria. Cox regression and competing risk models were used for survival analysis. A p value <0.05 was considered statistically significant. Results: 8,137 patients met inclusion criteria and were evaluated. A median of 6 LNs were examined in this cohort. Patients who underwent pneumonectomy and lobectomy had more LNs examined than those who had sub-lobar resections. Higher number of LNs examined was associated with better overall survival (OS) and lung cancer specific survival (LCSS), at a plateau of 8 LNs for both outcomes (Table). Having mediastinal LNs examined also resulted in increased OS and LCSS (p<0.05). Conclusions: The pathologic assessment of LNs in surgical specimens is often suboptimal. Examining more LNs may have increased the likelihood of correct staging. Lower numbers of LNs examined probably result in understaging. Examining 8 or more total LNs and mediastinal LNs examined improved both OS and LCSS. [Table: see text]
Randomized phase II trial comparing two schedules of thoracic radiotherapy (TRT) in limited disease small-cell lung cancer (LD SCLC).
Authors: Grønberg Bjørn Henning , Halvorsen Tarje Onsoien , Fløtten Øystein , Brustugun Odd Terje , Brunsvig Paal , Aasebø Ulf , Bremnes Roy M. , Tollali Terje , Hornslien Kjersti , Aksnessæther Bjørg Yksnøy , Liaaen Erik Dyb , Sundstrøm Stein ,   Norwegian Lung Cancer Study Group
Published: March 2020

7027 Background: Concurrent chemotherapy and TRT is standard therapy for SCLC if all lesions can be included in a radiotherapy field (LD). Several schedules of TRT are used. One study showed that two fractions a day improved local control and overall survival (OS), but this schedule has not been compared to a commonly used 3 wks schedule. Methods: Eligible pts had LD SCLC and PS 0-2. Pleural fluid was accepted if negative cytology. Pts received 4 cycles of PE (cisplatin 75 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 q 3 wks) and were randomly assigned to 3 wks of 3D conformal TRT [A] 42 Gy (2.8 Gy x 1/day) or [B] 45 Gy (1.5 Gy x 2/day). TRT started 3-4 wks after the first PE. All responders received prophylactic cranial irradiation (PCI) 2 Gy x 15 ≤ 6 wks after last PE. Pts reported health related quality of life (HRQoL) on EORTC QLQ C30 + LC13. Primary endpoint: 1-year local failure. Secondary: OS, toxicity and HRQoL (dysphagia and dyspnea; a difference ≥ 10 points was considered significant). 75 pts were required in each arm to show a 30% improvement of local disease control with α=.05 and β=.8. Results: 159 eligible pts were enrolled at 18 sites in Norway May 05 – Jan 11 (A: 85, B: 74). Median age 60 (40-85); 52% men, 84 % PS 0-1, 11% pleural fluid. Mean no. of PE-cycles was 3.8, 97% completed TRT, 82 % PCI (no difference between arms). Response rates were similar (A: 92%, B: 94%; p=.8), but more pts on Arm B had CR (A: 13%, B: 35%; p=.01). There was no difference in local failure as first site of progression at 1 year (A: 17%, B: 12%; p=.4) or 1-year PFS (A: 44%, B: 50% ; p=.4). There was similar grade 3-4 esofagitis (A: 33%, B: 37 %; p=.7) and pneumonitis (A: 6 %, B: 7 %; p=.9). 2 pts (1 on each arm) died from pneumonitis. Pts in Arm B reported more dysphagia (A: 64 points, B: 73 points), but not more dyspnea (A: 29 points, B: 28 points). 1-year OS was similar (A: 77%, B: 76%; p=.9). Currently, 2-year survival among those followed ≥ 2 years (n=130) favors Arm B (A: 40%, B: 55%; p=.09) and so far (all pts followed ≥ 1-year; 103 events) median OS favors Arm B (A: 18.7 mos, B: 26.6 mos; p=.34). Conclusions: Twice daily TRT resulted in more CRs, slightly more dysphagia, similar 1-year local control and 1-year PFS. There are indications of improved 2-year and median OS in this arm.
Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma (MPM).
Authors: Krug Lee M. , Wozniak Antoinette J. , Kindler Hedy Lee , Feld Ronald , Koczywas Marianna , Morero Jose Luis , Rodriguez Cristina P. , Ross Helen J. , Bauman Julie E. , Orlov Sergey V , Ruckdeschel John C. , Mita Alain C. , Fein Luis , Fernandez Cristian , Hall Robert , Kawabe Takumi , Sharma Sunil 
Published: March 2020

7029 Background: CBP501, a synthetic duodecapeptide, enhances the cytotoxicity of cisplatin in cell lines and xenografts, including NCI-H226 human mesothelioma. CBP501 increases cisplatin influx into tumor cells through an interaction with calmodulin, and inhibits cell cycle progression by abrogating DNA repair at the G2 checkpoint. Phase I clinical trials combining CBP501 with cisplatin alone or with pemetrexed showed acceptable safety profiles and suggested activity. The most common toxicity of CBP501 is infusion-related urticaria, which is easily managed with diphenhydramine. Methods: Chemotherapy-naive patients with unresectable MPM were stratified by histology (epithelioid vs other) and performance status (PS 0-1 vs 2) and randomized 2:1 to Arm A: pemetrexed/cisplatin plus CBP501 25 mg/m2 IV (42 pts planned), or Arm B: pemetrexed/cisplatin alone at standard doses (21 pts planned). Patients continued on treatment until progression or intolerance; no maintenance therapy was delivered. The primary endpoint is progression free survival (PFS) in Arm A; if > 23 of the 42 patients remain free of progression more than 4 months, the combination will be deemed worthy of further study. In addition to standard CT imaging to assess response and PFS, PET scans, pulmonary function tests, and mesothelin levels were performed. Results: Enrollment was completed in October 2011. 65 pts from 14 institutions were randomized, and 63 were treated. Patient characteristics in the two arms were similar and as follows: median age 65, 82% male, 71% epithelioid histology, 8% PS2. Grade 3/4 treatment-related toxicities were uncommon, no different than expected from standard chemotherapy, and comparable in the two arms. 70% of patients treated with CBP501 had infusion reactions, all grade 1-2. The best overall response rate in evaluable patients (modified RECIST, investigator assessed) was 12/37 (32%) (95% CI 18-50) in Arm A, and 3/22 (14%) (95% CI 3-35) in Arm B. The median number of chemotherapy cycles was 5.5 in Arm A, 5 in Arm B. Conclusions: Data on the primary endpoint of PFS in Arm A are maturing and will be presented at the meeting.
Phase II study of cixutumumab (IMC-A12) in thymic malignancies.
Authors: Rajan Arun , Riely Gregory J. , Carter Corey Allan , Thomas Anish , Khozin Sean , Bergagnini Isabella , Berman Arlene W , Scepura Barbara , Szabo Eva , Lee Min-Jung , Trepel Jane B. , Browne Sarah K , Pancholi Minjal J , Cao Liang , Chen Helen X. , Giaccone Giuseppe 
Published: March 2020

7033 Background: The IGF-1 receptor (IGF-IR) is expressed in thymoma (T) and thymic carcinoma (TC). Prolonged SD has been seen with anti-IGF-IR therapy in thymic tumors in phase I trials. Cixutumumab (C) is a fully human IgG1 monoclonal antibody (ab) that targets IGF-IR. Methods: Patients (pts) with recurrent T or TC, PS 0-2, measurable disease, and normal organ function received C at 20 mg/kg IV q3wks until progression or intolerable toxicity. Primary endpoint was response rate. Correlative studies included immune cell subset (central memory, effector memory, naïve and regulatory T cells), circulating endothelial progenitor (CEP) cell, serum IGF-1 and IGF-IR in PBMCs, anticytokine ab, and tumor mutational analysis. Results: Forty-five pts enrolled from two centers (20 female, T=33, med age 52 yrs, range, 26-86). Median number of prior systemic treatments: 3 (range, 1-11). Median number of cycles of C administered: 6 (range, 1-41). In 30 evaluable T pts there were 4 (13%) PR, 23 (77%) SD, and 3 (10%) PD. Corresponding numbers in 12 TC pts were 0, 5 (42%) and 7 (58%). Median PFS for T and TC was 40 and 9 wks respectively. C-related grade 3/4 AEs were hyperglycemia (8%), hyperuricemia, weight loss, lipase elevation, chest wall pain (5% each) and AST elevation (3%). Two pts died while on study: one due to respiratory insufficiency related to T after 5 cycles and one due to worsening myasthenia and an acute coronary event after 13 cycles. In 8 of 33 T pts autoimmune (AI) symptoms developed (4 new-onset) due to immune thrombocytopenic purpura, myositis, myocarditis, colitis, PRCA and food allergy. In the first 13 pts a trend towards increased numbers of central and effector memory T cells and a decrease in naïve T cells and CEPs was seen. High-titer anticytokine abs, including anti-IFNa, anti-IL-12, and anti-IL-17A, were found in 13/27 pts tested. No EGFR, KRAS or BRAF mutation, HER2 amplification or ALK translocations were detected in 11 tumors analyzed. Conclusions: C monotherapy is well tolerated and active in T. Accrual will continue until 37 T pts are enrolled. Activity in TC is unworthy of further investigation. CEP and immune cell subset analysis suggests therapy may impact angiogenesis and immune response. Development of AI symptoms during treatment needs further evaluation.