scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Franziska M. Müller ◽  
Anna M. Meyer ◽  
Lena Pickert ◽  
Annika Heeß ◽  
Ingrid Becker ◽  
...  

Older persons often loose independence during hospitalization. This analysis aimed at retrospectively evaluating the effects of a pilot individualized multidimensional intervention (IMI) on the comprehensive geriatric assessment (CGA)-based prognosis of older multimorbid patients in an acute internal medicine setting. Records from 72 patients aged 65 years and above who received the IMI were compared to those from 403 patients who received standard of care (SOC). All patients had undergone the CGA-based Multidimensional Prognostic Index (MPI) calculation on admission and at discharge. Patients were divided into three risk groups according to MPI score: Low-risk (MPI-1, 0-0.33), medium-risk (MPI-2, 0.34-0.66) and high-risk (MPI-3, 0.67-1). From admission to discharge, IMI patients showed significant improvements in their MPI score (P=0.014) and subdomains compared to SOC. This was particularly evident in MPI-2 and MPI-3 as well as in patients with poorer functions on MPI admission subdomains. An early geriatric intervention during hospitalization for disease-specific treatments in internal medicine settings improves overall individual prognosis in older multimorbid patients. Prospective randomized studies are needed to confirm these preliminary retrospective observations.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2718-2718
Author(s):  
Yuankai Shi ◽  
Bo Jia ◽  
Xiaohui He ◽  
Youwu Shi ◽  
Mei Dong ◽  
...  

Abstract Background Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare and distinct subtype of non-hodgkin lymphoma (NHL). The frequency was higher in Asia than in western countries and it has become the most common subtype of peripheral T-cell lymphomas in China. The majority of ENKL patients present with early stage. Optimal treatment modalities and prognostic factors for localized ENKL have not been fully defined. This study aimed to evaluate the optimal treatment strategy and prognostic factors for localized ENKL patients. Methods Between 2003 and 2013, three hundred and five patients with stage IE/IIE ENKL were comprehensively analyzed in this study. A total of 180 patients received combined chemoradiotherapy, with 111 patients received radiotherapy alone and 14 patients recieved chemotherapy alone. Chemotherapy regimens include GDP (gemcitabine, cisplatin, and dexamethasone), CHOP (epirubicin, cyclophosphamide, vincristine, and prednisolone) and other regimens. A total dose of 50 Gy to the primary tumor was considered as radical dose for ENKL, and additional 5 to 10 Gy was administered as a boost to the residual disease. Results The complete response (CR) rate for patients received chemoradiotherapy (n=175) was significantly higher than that for patients received radiotherapy alone (n=102) (89.1 % vs.77.5 %, P = 0.009) or chemotherapy alone (n=14) (89.1 % vs.21.4 %, P< 0.001). The median follow up time for all 305 patients was 38.7 (1.1 to 393) months. For 228 stage IE paranasal extension or IIE patients, 3-year overall survival (OS) in combined chemoradiotherapy (n=154), radiotherapy alone (n=60) and chemotherapy alone (n=14) groups were 85.7%, 73.3% and 57.1% respectively (chemoradiotherapy vs. radiotherapy, P=0.003; chemoradiotherapy vs. chemotherapy, P<0.001). For patients received combined chemoradiotherapy, GDP regimen (n=54) (included 10 patients with pegaspargase) could significantly improve 3-year progression-free survival (PFS) compared with CHOP-like (n=110) (included 10 patients with asparaginase) (88.9% vs. 70.9%, P =0.015).Patients received radiotherapy first followed by chemotherapy (n=84) was associated with superior 3-year PFS compared with patients initially received chemotherapy (n=96) (81.0% vs. 69.8%, P=0.034). But for 54 patients received GDP regimen, induction chemotherapy (n=17) could increase 3-year PFS (100.0% vs. 83.8%, P=0.112) and OS (100.0% vs. 86.5%, P=0.180). We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes. The 3-year OS rates were 93.5%, 85.0% and 62.2% respectively for patients with no risk factors, 1 or 2 factors and 3 factors (P<0.001). Conclusions Combined chemoradiotherapy is the most optimal therapy strategy for stage IE paranasal extension or IIE ENKL patients. GDP or combined with pegaspargase regimen shows promising efficacy, significant superior to the traditional CHOP regimen. The sequence of chemotherapy and radiotherapy for patients received novel chemotherapy regimens still needs further assessment in phase 3 clinical trials. We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes and this novel prognostic model may better predict prognosis than previous International Prognostic Index (IPI) and Korean Prognostic Index (KPI) score for ENKL patients with limited stage. Disclosures No relevant conflicts of interest to declare.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 11-11
Author(s):  
J. L. Dikken ◽  
C. J. Van De Velde ◽  
M. Verheij ◽  
R. Baser ◽  
M. Gonen ◽  
...  

11 Background: The risk of dying of cancer is highest in the first two years after a curative resection for gastric cancer. Therefore, the prognosis of patients who did not recur in the first two years is improved because they survived this critical period, a phenomenon called conditional survival. The US-derived gastric cancer nomogram predicts disease-specific survival (DSS) based on pathological variables. However, a disease-free interval after surgery, which improves the prognosis, is not captured by the nomogram. Therefore, it has only been used directly after surgery and not in the follow-up setting. The purposes of this study were to develop a conditional survival nomogram for 1, 2 and 3-year survivors (step 1) and to test if the introduction of follow-up variables would improve predictive accuracy of the nomogram in the follow-up setting (step 2). Methods: In a combined US-Dutch population of 1642 patients who underwent an R0 resection for gastric cancer and for whom the old nomogram variables were available, a conditional survival nomogram based on the original variables was developed for one (N=1147), two (N=879) and three (N=721) year survivors (step 1). To improve predictive accuracy in the follow-up setting, weight loss, performance status (PS), hemoglobin (HGB), and albumin (ALB) at one year after resection were retrospectively collected and added to the baseline variables in a new nomogram (step 2). Results: The conditional survival nomograms for 1, 2 and 3-year survivors (step 1) showed a high predictive accuracy in the calibration plots. Surviving one, two and three years shows a median improvement of 5-year DSS of 4%, 9% and 14% respectively. The introduction of weight loss, PS, HGB, and ALB at one year after surgery (step 2) did not improve this nomogram, but availability of these variables was limited. Conclusions: A strongly predictive conditional survival nomogram was developed, giving an improved prognosis for 1, 2 and 3-year survivors of gastric cancer. Introduction of variables available at one year after resection did not further improve this nomogram. This might be caused by the limited availability of follow-up data, as well as the strong predictive accuracy of the original variables. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3070-3070
Author(s):  
Daphne Day ◽  
Anna Spreafico ◽  
Stephanie Lheureux ◽  
Albiruni Ryan Abdul Razak ◽  
Aaron Richard Hansen ◽  
...  

3070 Background: We previously developed the PM-IPI (ECOG performance status [PS] > / = 1, albumin < lower limit of normal [LLN] and > 2 metastatic sites) from a retrospective cohort of 192 pts treated in phase I IO trials (development cohort). The PM-IPI prognosticated for overall survival (OS), 90-day mortality (90DM) and was associated with improved overall response rate (ORR) and progression free survival (PFS). Our aim was to prospectively validate the PM-IPI in an independent cohort of pts treated on IO trials. Methods: We included 152 consecutively treated advanced solid tumor pts at PM from Aug 2015 to Aug 2016 in 24 IO early phase trials, targeting immune checkpoints and/or co-stimulatory molecules. Pts from the development cohort were excluded. The ability of the PM-IPI to prognosticate OS and 90DM, and predict PFS and ORR was compared with the previously published Royal Marsden Hospital prognostic score (RMI: albumin < 35g/L, LDH > upper limit of normal and > 2 metastatic sites) using the C-index (0.5 = no discrimination, 1 = perfect discrimination) and Area Under the Curve (AUC). Results: Median age was 59y (range 20-86), 28%/72% of pts were ECOG PS 0/1, and 88% had at least 1 prior systemic therapy (range 0-7). The most common tumor sites were gastrointestinal (23%), gynecological (16%), head and neck (15%) and urological (10%). Median PFS and OS were 9.0 and 39.7 wk respectively and 90DM was 14%. ORR was 7% by RECIST 1.1, immune related RECIST or immune related response criteria. In multivariable analysis, ECOG PS > / = 1 (HR 2.7, p = 0.01), albumin < LLN (HR 2.1, p = 0.01) and > 2 metastatic sites (HR 1.8, p = 0.04) were independently prognostic for OS. Pts with a PM-IPI score of 2-3 compared to 0-1 had significantly shorter OS (HR 3.3, p < 0.0001), PFS (HR 1.7, p = 0.005) and higher 90DM (OR 12.2, p = 0.019), and a trend towards lower ORR (OR 0.4, p = 0.15). The prognostic performance of PM-IPI was superior to the RMI for OS and 90DM, but not PFS and ORR (Table). Conclusions: In this independent validation cohort, the PM-IPI prognosticated for OS and 90DM and was associated with PFS. Validation in a large external cohort is ongoing. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6034-6034 ◽  
Author(s):  
Panagiota Economopoulou ◽  
Nikolaos Spiridon Spathas ◽  
George Papaxoinis ◽  
Maria Anastasiou ◽  
Maria Gkotzamanidou ◽  
...  

6034 Background: Hyperprogressive disease (HPD) refers to paradoxical acceleration of tumor growth kinetics (TGK) after initiation of treatment with anti- PD-1/PD- L1 agents and has been reported across tumor types in 4-29% of patients using different definitions. Preliminary data suggest that HPD might affect response to subsequent therapies. Methods: We compared TGK prior and TGK upon immunotherapy (IO) in 62 patients (pts) with recurrent/metastatic (R/M) HNSCC treated with PD-1/PD-L1 inhibitors. The TGK ratio (TGKR, ratio of tumor growth velocity before and upon treatment) was calculated. The first imaging assessment was performed 3 months (mo) after IO initiation. HPD was defined as 1. Radiological HPD (TGKR≥2) or 2. Clinical HPD (Disease-related rapid clinical deterioration post IO). Results: After median follow-up of 12.3 mo (range, 0.4-28.1), 43 pts progressed and 38 died. Median PFS was 2.8 mo (95%CI, 2.2-3.4) and median OS 8.6 mo (95%CI, 4.2-12.9). HPD was observed in 16 pts (25.8%), while 15 pts had early PD (Time to Treatment failure, TTF < 3 mo) and 31 late PD (TTF > 3mo). Among 16 pts with HPD, 11 had radiological HPD and 10 had clinical HPD. 4 pts had both clinical and radiological HPD. Pts with late PD had median OS 11.3 mo (95%CI, 9.3-13.3), those with early PD 5.2 mo (95%CI, 3.1-7.3 months) and those with HPD 5.1 mo (95%CI, 4.4-5.9) (p < 0.005). Regarding post-progression OS, pts with late PD had median 11.3 mo (95%CI 0-22.8), those with early PD 2.5 mo (95%CI 0.6-4.4) and those with HPD 4.2 mo (95%CI 1.7-6.7) (p = 0.001). Pts with HPD had a trend for longer median post-progression OS compared to pts with early PD (p = 0.121). Median PFS with chemotherapy after immunotherapy failure was 3.0 mo (95%CI 2.4-3.6) for pts with late PD, 2.1 mo (95%CI 0.9-3.4) for pts with early PD and 6.1 mo (95%CI 3.0-9.3) for those with HPD (p = 0.040). HPD was associated with longer median PFS with chemotherapy compared to pts with early PD (p = 0.016), while the difference in median PFS with chemotherapy between pts with HPD and late progressors was non-statistically significant (p = 0.260). Conclusions: Radiological or clinical HPD was observed in 25.8% of patients with R/M HNSCC treated with IO. Early progression to immunotherapy is an important predictor of short survival, while HPD was associated with improved PFS to subsequent chemotherapy.


2019 ◽  
Vol 73 (12) ◽  
Author(s):  
Anna Maria Meyer ◽  
Giacomo Siri ◽  
Ingrid Becker ◽  
Thomas Betz ◽  
August W. Bödecker ◽  
...  

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 465-465
Author(s):  
Oren Smaletz ◽  
Matias Chacon ◽  
Ludmila de Oliveira Koch ◽  
Daniela Regina de Carvalho Rocha ◽  
Fernanda Camila Cardoso

465 Background: Prospective studies with sunitinib in mRCC have shown median progression-free survival (mPFS) of 11 months (first line) and 8.3 months (second line). In order to identify patients with LTB with SU, we describe the clinical characteristics of patients with mRCC treated with SU with an mPFS of 15 months or more. Methods: This is a retrospective chart review of patients with mRCC treated with SU in two hospitals, Alexander Fleming Institute Buenos Aires in Argentina and Hospital Israelita Albert Einstein in Sao Paulo, Brazil. Inclusion criteria included patients treated with SU who had a PFS of at least 15 months. Results: Between September 1995 and August 2009, 29 cases were identified. Patient demographics were: median age of 56 years, 65% male, 96% with previous nephrectomy, Eastern Cooperative Oncology Group performance status (PS) of either 0 (52%) or 1 (48%), 93% had clear cell histology, 69% received prior systemic therapy, and 78% had ≤ 2 metastatic sites (mostly in the lungs, liver and bone). Patients were started on SU 50 mg 4 weeks on treatment/2 weeks off treatment (4/2) (n=26) or 37.5 mg 6 weeks continuous dosing (n=3). For those patients starting on 4/2, dose reduction was necessary in 59% of the patients to maintain SU therapy. Median duration of therapy was 23.7 months. During treatment, 24 patients (83%) developed hypertension. Response rates were as follows: complete response 7% (n=2), partial response 38% (n=11), stable disease 52% (n=15); data missing for one patient. Conclusions: LTB is seen in patients who are young, have good performance status, and either 1 or 2 metastatic sites. Dose reductions are common in order to maintain treatment while benefiting from SU. Treatment with SU as either first- or second-line therapy did not appear to influence outcome. Hypertension is a common finding and serves as a predictive marker during treatment, but study limitations preclude the identification of pre-treatment predictive factors.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7544-7544 ◽  
Author(s):  
Amy S. Ruppert ◽  
Jesse G. Dixon ◽  
Gilles A. Salles ◽  
Anna K. M. Wall ◽  
David Cunningham ◽  
...  

7544 Background: Great heterogeneity in survival exists for patients (pts) newly diagnosed with aggressive BCL. Three scoring systems based on simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the international prognostic index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We studied BCL pts treated with R-CHOP to determine which scoring systems best identifies subgroups with poor outcomes that might benefit from new approaches. Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performs best in risk-stratifying pts with aggressive BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI appears incremental, and IPI may remain a valuable alternative. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to define high risk groups where targeted novel approaches are needed most. [Table: see text]


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5072-5072
Author(s):  
Michele Spina ◽  
Ulrich Jaeger ◽  
Joseph A Sparano ◽  
Renato Talamini ◽  
Giuseppe Rossi ◽  
...  

Abstract Abstract 5072 Background: The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL. Methods: In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT. Results: Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III-IV) disease and 57% of pts had an age-adjusted international prognostic index >2. Fifty-two out of 74 pts (70%) achieved a complete remission (CR), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Four cases of secondary tumors have been observed. No case of late pulmonary or cardiac toxicity has been reported. Conclusions: The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured. Disclosures: No relevant conflicts of interest to declare.


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