scholarly journals 565 Combinatorial HSCs and anti-PD-1 therapy in microsatellite stable colorectal cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A594-A594
Author(s):  
Bayli DiVita Dean ◽  
John Figg ◽  
Laura Falceto Font ◽  
Connor Francis ◽  
Duane Mitchell ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Treatment Control ◽  
University Of Florida ◽  
Hematopoietic Stem ◽  
Tumor Implantation ◽  
Mhc Ii ◽  
Log Rank Test ◽  
The Us ◽  
The Right

BackgroundColon cancer (CRC) is the second leading cause of cancer-related deaths in the US. CRC incidence is on the rise and there is an alarming increase in young onset CRC cases. Immune checkpoint inhibitors (ICIs) have yielded promising anti-tumor results in microsatellite instable high (MSI-high) patients, which represent only 15% of tumors. The remaining 85% are denoted as microsatellite stable (MSS) and are unresponsive to ICI. Using a murine glioma model, our group has previously found the combination of anti-PD-1 and a transfer of hematopoietic stem cells (HSCs) can sensitize mice that are resistant to anti-PD-1 alone. We evaluated survival after treatment with this combinatorial platform 3 or 5 days post-implantation in subcutaneous CRC-bearing mice and also phenotyped the splenic compartment of mice at endpoint.Methods1x106 MSS CRC cells, CT26, were subcutaneously injected into the right flank of BALB/cJ mice. 3 or 5 days later, HSCs were isolated from naïve BALB/cJ mice and injected through the tail vein into CT26-bearing mice and were also given 10 mg/kg anti-PD-1. Mice were given 3 additional doses of anti-PD-1 for a total of doses either every 3 or 5 days. Mice were sacrificed when tumors reached 1.5 cm at its widest point and spleens were excised and stained for flow cytometry.ResultsWhen mice were treated with HSC/anti-PD-1 3 days post-tumor implantation, we observed a statistically significant increase in survival in mice that received combinatorial HSCs and anti-PD-1 relative to no treatment control mice (p=0.0034, Mantel-Cox long-rank test) as well as mice that received HSCs alone (p=0.0462, Mantel-Cox log-rank test. In the same 3 day cohort, no differences in the frequency of T cell populations were observed. However, we found mice that received this combination therapy had a significant increase in the frequency of splenic CD11c+ MHC II+ dendritic cells (DCs) relative to no treatment control mice (p=0.0364, Mann-Whitney t test). When mice were treated with HSC/anti-PD-1 5 days post-tumor implantation, we found a statistically significant increase in survival of mice treated with combinatorial HSCs and anti-PD-1 compared to no treatment control mice (p=0.0024, Mantel-Cox log-rank test) and relative to mice that received HSC monotherapy (p=0.0462, Mantel-Cox log-rank test).ConclusionsThese results suggest combinatorial HSCs and anti-PD-1 represents a promising therapeutic axis in a murine model of MSS CRC. In addition, the increase in splenic DCs suggests the mechanism behind this anti-tumor response may be expansion of DCs within the periphery.Ethics ApprovalAll animal work approved through University of Florida IACUC # 201910777

Human Herpes Virus 6 Infection in 54 Patients after Allogeneic Hematopoietic Stem Cell Transplantation: Clinical Manifestations and Outcome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3899-3899
Author(s):  
Raffaella Greco ◽  
Lara Crucitti ◽  
Sara Racca ◽  
Roee Dvir ◽  
Francesca Lorentino ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Clinical Manifestations ◽  
Rank Test ◽  
P Value ◽  
Hematopoietic Stem ◽  
Clinical Complications ◽  
Log Rank Test ◽  
Blue Line

Abstract BACKGROUND: Human herpesvirus type 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic hematopoietic stem cell transplantation (AlloSCT). HHV-6 is a member of the beta herpesvirus subfamily (genus Roseolovirus). HHV-6 infection is recognized as the cause of a febrile disease and exanthem subitum in early childhood. Approximately 60% of solid organ transplant and 40% of patients after alloSCT experienced HHV-6 reactivation. Reported clinical manifestations of HHV-6 infection in transplanted patients are skin rash, interstitial pneumonia, bone marrow suppression and encephalitis. Moreover, some clinical reports suggest that HHV-6 can facilitate the occurrence of severe clinical complications of alloSCT, increasing transplant-related mortality. METHODS: From January 2009 to February 2013, we retrospectively evaluated 54 consecutive adult patients (median age 50 years) who developed positivity to HHV-6 after alloSCT for high-risk hematological malignancies. Stem cell donors were family haploidentical (37), HLA identical sibling (8), unrelated volunteer (6), cord blood (3). The viral load was determined by quantitative PCR (Nanogen Advanced Diagnostic S.r.L) in cell-free body fluids such as plasma, bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), bone marrow (BM) aspirates or in gastrointestinal biopsies. RESULTS: Median time from alloSCT to HHV-6 reactivation was 34 days (range: 0-705). Thirty-one patients presented HHV-6 positive in plasma, 9/54 in BM, 33/54 in gut biopsies or BAL, 7/54 in CSF. At the time of viral positivity all pts were receiving acyclovir as viral prophylaxis except five. Twenty-nine patients had acute graft versus host disease (GvHD). Twenty-two out of these twenty-nine patients experienced a grade III-IV acute GvHD, requiring high dose steroids in twenty-six cases. A concomitant CMV positivity was detected in 15/54 patients. The median absolute count of CD3+ lymphocytes was 207 cells/mcl. In 52/54 cases we reported HHV-6 clinical manifestations: fever (43), skin rash (22), hepatitis (19), diarrhoea (24), encephalitis (10), BM suppression (18), delayed engraftment (11). HHV-6 positivity led to antiviral pharmacological treatment in 37/54 cases, using as first choice therapy foscarnet. Amongst the total fifty-four patients with documented HHV-6 positivity thirty-one solved the clinical event. However the mortality rate was relatively high in this population (overall survival (OS) ±SE at 1 year after HHV-6 reactivation was 38% ± 7%), mainly related to severe infections or GvHD. A better OS is significantly associated with CD3+ cells ≥200/mcl at the time of HHV-6 reactivation (fig 1) (OS at 1 year 63% compared to 11% for patients with CD3 <200/mcl; HR: 0.27, 95% CI 0.12-0.54, p=0.0002). The overall survival of these patients was also positively affected by the absence of acute GvHD grade III-IV at time of viral reactivation (HR: 0.03, 95% CI 1.08-4.03, p=0.03) and by the complete disease remission at time of HSCT (HR:0.26, 95% CI 0.07-0.89, p=0.03). In this analysis the overall survival was not significantly influenced by steroids administration (HR: 1.36, 95% CI 0.71-2.60, p=0.36), time after alloSCT (HR: 1.30, 95% CI 0.51-3.33, p=0.59), type of antiviral prophylaxis (HR: 1.02, 95% CI 0.45-2.33, p=0.96), plasma viral load (HR:1.18, 95% CI 0.51-2.76, p=0.69) and organ involvement (HR:1.14, 95% CI 0.59-2.20, p=0.70). CONCLUSIONS: This retrospective study confirms a correlation of HHV-6 with high morbidity and mortality rates after alloSCT, thus suggesting a regular HHV-6 monitoring in alloSCT recipients. The regular monitoring of HHV-6 DNA, using a real-time PCR assay, may be useful for identifying active HHV-6 infection and for the introduction of a pre-emptive treatment, possibly reducing the incidence of the most severe clinical complications. Despite HHV-6 detection typically occurred early after alloSCT, a better immune reconstitution has the potential to improve clinical outcome. Figure 1: Overall survival after alloSCT in HHV-6 positive patients: green line showed patients with more than 200/mcl CD3+ cells, blue line the ones with less than 200/mcl CD3+ cells at HHV-6 reactivation. P value is provided by Log Rank test. Figure 1:. Overall survival after alloSCT in HHV-6 positive patients: green line showed patients with more than 200/mcl CD3+ cells, blue line the ones with less than 200/mcl CD3+ cells at HHV-6 reactivation. P value is provided by Log Rank test. Disclosures Bonini: MolMed S.p.A.: Consultancy.

High-Dose Cyclophosphamide + G-CSF Mobilization Regimen Have Higher Anti-Myeloma Effects Than G-CSF Alone Regimen – Single Institutional Study in 147 Myeloma Patients From Japan

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2007-2007
Author(s):  
Akira Tanimura ◽  
Masataka Takeshita ◽  
Atsushi Sato ◽  
Junichiro Takano ◽  
Hideaki Kitahara ◽  
...  
Keyword(s):  
Disease Control ◽  
Therapeutic Intervention ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Staging System ◽  
Rank Test ◽  
P Value ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Log Rank Test

Abstract Abstract 2007 Background: High-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF) and G-CSF alone have been used to mobilize hematopoietic stem cells (HSCs) for autologous SC transplantation (ASCT) in multiple myeloma (MM). However, which regimen is better is unknown; anti-myeloma effects of HD-CY + G-CSF have not been established. From January 1999 to June 2009, we administered HD-CY+G-CSF but changed to G-CSF alone during July 2009–December 2010. We retrospectively assessed HSC collection efficacy, complications, and anti-myeloma effects of these regimens. Patients and methods: We analyzed 147 MM patients from whom HSCs were to be collected at our institute. For mobilization, 115 patients were administered HD-CY (4 g/m2)+G-CSF (600 mg/body filgrastim or 500 mg/body lenograstim) and 32 were administered G-CSF alone (same dose as HD-CY). Here, 17 patients received therapeutic intervention between mobilization and transplantation without disease progression (PD). To avoid the patient outcome effect, we defined event- and progression-free survivals (EFS and PFS). EFS was defined as PD, death, or therapeutic intervention without PD. PFS was defined as PD or death, where therapeutic intervention without PD was used as a censor. Both were calculated from the start of mobilization. For analyzing response by mobilization, patients receiving therapeutic intervention without PD were excluded. Response was evaluated in those not receiving therapeutic intervention without PD or in whom response could not be evaluated before ASCT. Thalidomide was administered as maintenance therapy to 14 and 6 patients in the HD-CY+G-CSF and G-CSF groups after ASCT. Thalidomide administration was used as a censor. Results: Vincristine, doxorubicin, and dexamethasone (VAD) and HD dexamethasone (HDD) therapies were administered as induction therapy (VAD for 117, HDD for 2, and both for 11). New (bortezomib or thalidomide) and alkylating agents were administered to 7 and 13 patients, respectively. Before mobilization, 26 patients received radiotherapy; none were administered lenalidomide. No statistical difference was seen in baseline characteristics (Durie-Salmon stage, International staging system, interval from diagnosis to mobilization, disease control, and previous therapies) between both groups. However, patients mobilized by G-CSF alone were significantly older. Among 147 patients, 121 underwent planned ASCT. Of the 17 receiving therapeutic intervention without PD, 13 and 4 belonged to the HD-CY+G-CSF and G-CSF groups, respectively. More than 2 × 106 CD34-positive cells/kg were collected from 93% and 75% patients in the HD-CY+G-CSF and G-CSF (p = 0.0079) groups, respectively. More than 4 × 106 CD34-positive cells/kg were collected from 84% and 69% in the HD-CY+G-CSF and G-CSF (p = 0.07). Mean HSC count was 11.4 × 106/kg in the HD-CY+G-CSF group and 4.5 × 106/kg in the G-CSF group (p = 0.0007). Among patients receiving HD-CY+G-CSF, 66% were treated with intravenous antibiotics; 3 suffered cardiac shock and 2 septic shock. However, among those receiving G-CSF alone, no severe complications were seen. Median hospitalization days were 21 and 8 for the HD-CY+G-CSF and G-CSF groups, respectively (p < 0.0001). In the HD-CY+G-CSF group, 16% improved in disease control before ASCT, 71% showed no change, and 13% progressed. However, no patient improved, 63% showed no change, and 27% progressed in the G-CSF group (p = 0.015). Median EFS was 25 months in the HD-CY+G-CSF group and 13 in the G-CSF group (fig 1, p value of log-rank test = 0.012). Median PFS was 28 months in the HD-CY+G-CSF group and 15 in the G-CSF group (fig 2, p value of log-rank test = 0.011). Median overall survival did not differ significantly. Conclusion: Regarding the safety and duration of hospitalization, G-CSF alone may be safer and beneficial. However, HD-CY+G-CSF was more effective as a mobilization regimen and showed higher anti-myeloma effects than G-CSF alone. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung

2021 ◽  
Vol 9 (2) ◽  
pp. e001999
Author(s):  
Elizabeth Dudnik ◽  
Samuel Kareff ◽  
Mor Moskovitz ◽  
Chul Kim ◽  
Stephen V Liu ◽  
...  
Keyword(s):  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Eastern Cooperative Oncology Group ◽  
Large Cell ◽  
Disease Diagnosis ◽  
Small Sample ◽  
Rank Test ◽  
Log Rank Test

BackgroundLittle is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC).Methods125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84). Overall survival since advanced disease diagnosis (OS DX) and OS since ICI initiation (OS ICI) were captured.ResultsWith a median follow-up of 11.8 months (mo) (IQR 7.5–17.9) and 6.0mo (IQR 3.1–10.9), 66% and 76% of patients died in groups A and B, respectively. Median OS DX was 12.4mo (95% CI 10.7 to 23.4) and 6.0mo (95% CI 4.7 to 9.4) in groups A and B, respectively (log-rank test, p=0.02). For ICI administration, HR for OS DX was 0.59 (95% CI 0.38 to 0.93, p=0.02—unadjusted), and 0.58 (95% CI 0.34 to 0.98, p=0.04—adjusted for age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), presence of liver metastases and chemotherapy administration). In a propensity score matching analysis (n=74; 37 patients in each group matched for age and ECOG PS), median OS DX was 12.5 mo (95% CI 10.6 to 25.2) and 8.4 mo (95% CI 5.4 to 16.9) in matched groups A and B, respectively (log-rank test, p=0.046). OS ICI for patients receiving ICI as monotherapy (n=36) was 11.0 mo (95% CI 6.1 to 19.4).ConclusionsWith the limitations of retrospective design and small sample size, the results of this real-world cohort analysis suggest a positive impact of ICI on OS in aLCNEC.

scholarly journals Evaluation of Response to Immune Checkpoint Inhibitors Using a Radiomics, Lesion-Level Approach

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6050
Author(s):  
Chorog Song ◽  
Hyunjin Park ◽  
Ho Yun Lee ◽  
Seunghak Lee ◽  
Joong Hyun Ahn ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Ct Scans ◽  
Advanced Lung Cancer ◽  
Rank Test ◽  
Multivariable Logistic Regression Analysis ◽  
Log Rank Test ◽  
Lesion Level ◽  
Hyperprogressive Disease

Conventional methods to determine the response to immune checkpoint inhibitors (ICIs) are limited by the unique responses to an ICI. We performed a radiomics approach for all measurable lesions to identify radiomic variables that could distinguish hyperprogressive disease (HPD) on baseline CT scans and classify a dissociated response (DR). One hundred and ninety-six patients with advanced lung cancer, treated with ICI monotherapy, who underwent at least three CT scans, were retrospectively enrolled. For all 621 measurable lesions, HPDv was determined from baseline CT scans using the tumor growth kinetics (TGK) ratio, and radiomics features were extracted. Multivariable logistic regression analysis of radiomics features was performed to discriminate DR. Radiomics features that significantly discriminated HPDv on baseline CT differed according to organ. Of the 196 patients, 54 (27.6%) had a DR and 142 (72.4%) did not have a DR. Overall survival in the group with a DR was significantly inferior to that in the group without a DR (log rank test, p = 0.04). Our study shows that lesion-level analysis using radiomics features has great potential for discriminating HPDv and understanding heterogeneous tumor progression, including a DR, after ICI treatment.

scholarly journals External Validation of the Revised PAM Score for Patients with AML Scheduled for Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3495-3495
Author(s):  
Frederike Kollinger ◽  
Jan Moritz Middeke ◽  
Maria Hardtmann ◽  
Christian Klesse ◽  
Friedrich Stölzel ◽  
...  
Keyword(s):  
External Validation ◽  
Disease Stage ◽  
Rank Test ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Log Rank Test ◽  
Donor Type ◽  
Primary Induction ◽  
Induction Failure ◽  
Reduced Intensity

Abstract Purpose Counselling of patients with AML about allogeneic hematopoietic stem cell transplantation (alloHSCT) is still an ambitious task in the light of the potential curative perspective after alloHSCT, poor outcomes after non-transplant approaches but a high risk of transplant-associated complications and still a significant risk of relapse even after HSCT. Several scores have been developed to predict outcome after HSCT, such as the HCT-CI and the Pre-transplant Assessment of Mortality (PAM) score. The PAM score has been revised recently, thereby acknowledging the shift to more frequently used reduced intensity conditioning. This score utilizes information on pts.age, donor type, disease risk, theserostatus for the CMV of pts.and donor, and the forcedexspiratory volume in the 1 second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent, large cohort of AML pts.who receivedalloHSCT within the last 12 years. Patients and Methods We selected all adult AMLpts.whoreceived the firstalloHSCTat the University Hospital of Dresden, a tertiary care hospital with a large transplant program, from January, 1, 2003 to July, 1, 2015.Pts.withhaplo-identical donors or after cord-blood transplantation were excluded. All patients gave their informed consent on analysing data. The PAM score was calculated as published (Au et al., BBMT 2015) and stratified into 4 groups: scores <17,scores17 to <24, scores 24 through 30, and scores >30. Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse-mortality (NRM) after alloHSCTwereanalyzed according to several factors known to impact outcome using the log-rank test for univariate comparison. Age, AML type (de novo vs. sAMLvs. t-MN), sex match (female donor/male recipient vs. all other), CMV match (negative/negative vs. all other), donor type (sibling vs. matched unrelated vs. mismatched unrelated), ELN risk classification, type of conditioning (RIC vs. MAC), disease stage (CR1 vs. primary induction failure vs. >= first relapse) and the PAM score as a continuous variable were selected a priori for multivariate Cox regression analyses. Results Overall, 544 pts.metthe inclusion criteria and were analyzed,the median age was 57 years (range, 18 to 76). Two-hundred-three pts.(37%) were treated with standard myeloablative conditioning (MAC) regimens while the remaining pts. received reduced intensity conditioning (RIC). Donors were siblings in 120 (22%), matched unrelated in 295 (54%) and mismatched unrelated donors in 129 (24%) pts. With a median follow up of 47 months (range, 1 to 161), the estimated OS for the whole cohort at five years was 43%, with a CIR of 30% and a NRM of 31% up to that time-point. The probability for OS at five years for pts.in PAM score group 0, 1, 2, and 3 was 65%, 50%, 33%, 22%, respectively (log-rank test, p= <.001). Both the CIR and NRM increased with increasing PAM scores (gray-tests, p= .005 and p= <.001, respectively). Notably, the PAM score contributed significantly to the prediction of OS even when added to a multivariate regression model which contained the single components of the score. In the final multivariate model, age (HR 1.02 per year, p= .004), disease stage (primary induction failure versus CR1, HR 1.5, p= .03), and the PAM score (HR 1.04, p= .03) had a significant impact on OS. Conclusion We validated the revised PAM for the prediction of OS after HLA-compatiblealloHSCTin a large, well characterised cohort of AMLpts.treatedat a large German transplantcenter. To the best of our knowledge, this is the first external validation of the revised PAM score. OS prediction based on this tool will be useful for counselling of futurepts.withAML. Figure OS after HSCT according to the PAM score Figure. OS after HSCT according to the PAM score Disclosures Middeke: Sanofi: Honoraria. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

Stem Cell Mobilization With Plerixafor + G-CSF In Comparison To Cyclophosphamide + G-CSF and Time-To-Progression After Autologous Stem Cell Transplantation For Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3354-3354
Author(s):  
Alfred L. Garfall ◽  
Andrew Dougherty ◽  
Dan T. Vogl ◽  
Brendan M Weiss ◽  
Adam D Cohen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Log Rank Test ◽  
Induction Regimen ◽  
Cell Mobilization

Abstract Background G-CSF in combination with either cyclophosphamide (G-Cy) or plerixafor (G-P) safely mobilizes hematopoietic stem cells of adequate quality and quantity for auto-SCT in patients with multiple myeloma. Few studies have examined the impact of mobilization regimen on post-transplant disease control, particularly since the availability of plerixafor. Methods We retrospectively compared time-to-progression (TTP) after single melphalan-conditioned (140-200 mg/m2) auto-SCT in a single-institution cohort in which stem cells were mobilized with either cyclophosphamide 3 gm/m2 + G-CSF 10 mcg/kg/day x 10-14 days (G-Cy, n=93) or G-CSF 10 mcg/kg/day x 5-9 days with addition of plerixafor 240 mcg/kg/day starting on day 5 (G-P, n=55). Choice of mobilization regimen was according to physician preference. All patients had symptomatic multiple myeloma and had completed induction therapy with a regimen containing bortezomib and/or lenalidomide/thalidomide. Transplants conducted from January 2010 to May 2013, when commercially-available plerixafor was first used at our institution, were included in the analysis. Patients receiving tandem or salvage transplants and patients receiving investigational therapies in conjunction with transplant were excluded. Maintenance therapy was prescribed at the discretion of the treating physician. Progression was scored according to IMWG criteria. Results The G-Cy and G-P cohorts were well matched for age, gender, and baseline multiple myeloma prognostic factors (see table). Cytogenetic data and beta-2-microglobulin measurements were not consistently available at baseline. Patients receiving G-P were more likely to have a >60 day interval between mobilization and transplant (P<0.0001) and >1 year interval between diagnosis and transplant (P=0.05). At time of transplant, hemoglobin was lower in the G-Cy group (P=0.0003), and platelet count was lower in the G-P group (P=0.035). Renal function at time of transplant was similar between the two groups. Patients in the G-P group were more likely to have received dose-reduced melphalan (<200 mg/m2) (p=0.03). The G-P group had higher ALC at day +15, which has been reported previously as a favorable prognostic factor for progression-free and overall survival. Median follow-up was 22 months. TTP was significantly different in the two groups (p=0.0095, log-rank test); median TTP was 25 months in the G-Cy group vs. 13 months in the G-P group (see figure). The difference in TTP remained significant when patients were excluded from the analysis who were transplanted more than 1 year after diagnosis (median TTP 26 vs. 13 months, P=0.0136 by log-rank test) or who were transplanted more than 60 days after mobilization (TTP 25 vs 13 months, P=0.0017 by log-rank test). Other variables that were significantly correlated with inferior TTP included IgA isotype (p=0.022) and receipt of >1 induction regimen (p=0.0077). In a univariate Cox regression, mobilization with G-P was associated with a hazard ratio of 2.1 (95% CI 1.2-3.9, p=0.011) for progression. In a multivariate Cox regression incorporating presence of IgA isotype, receipt of >1 induction regimen, mobilization regimen, age at transplant, time from diagnosis to transplant, time from mobilization to transplant, receipt of reduced melphalan dose, creatinine/hemoglobin/platelet count at time of transplant, ALC on day +15, and receipt of maintenance therapy, the association between G-P and inferior TTP was preserved (hazard ratio 2.8, 95% CI 1.3-6.0, p=0.007). The only other statistically significant variable was receipt of >1 induction regimen (hazard ratio 2.3, 95% CI 1.3-4.4, p=0.008). Receipt of maintenance therapy had a protective effect that approached statistical significance (hazard ratio 0.58, 95% CI 0.33-1.03, P=0.065). There were no significant differences in overall survival between the G-Cy and G-P groups. Conclusion Hematopoietic stem cell mobilization with G-P was associated with significantly shorter post-transplant TTP compared to G-Cy in this single-institution cohort of multiple myeloma patients. We cannot conclude whether this association is due to effects of the mobilization regimen or confounding variables not accounted for in our analysis. This association warrants examination in a larger, multi-institution cohort. Disclosures: Stadtmauer: Sanofi: Consultancy.

scholarly journals Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER–Medicare database

2021 ◽  
Vol 12 ◽  
pp. 204209862199127
Author(s):  
Abdulaali R. Almutairi ◽  
Marion Slack ◽  
Brian L. Erstad ◽  
Ali McBride ◽  
Ivo Abraham
Keyword(s):  
Logistic Regression ◽  
Elderly Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Advanced Melanoma ◽  
Sensitivity Analyses ◽  
Rank Test ◽  
Log Rank Test

Background: The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting. Methods: Elderly patients (age ⩾ 65 years) diagnosed with advanced melanoma between 2011 and 2015 and treated with anti-CTLA4 or anti-PD1 agents were identified from the Surveillance, Epidemiology, and End Results (SEER)–Medicare data. We estimated the risk of colitis from start of treatment up to 90 days from the last dose of therapy. We used the log-rank test and logistic regression with adjustment for potential confounders using the inverse probability of treatment weighting method. We conducted several sensitivity analyses. Results: A total of 274 elderly patients with advanced melanoma were included in our cohort. The risk of colitis was similar between anti-PD1 users and anti-CTLA4 users based on log-rank test ( p = 0.17) and logistic regression [odds ratio (OR) = 0.35, 95% confidence interval (95%CI) 0.04–2.79]. Sensitivity analyses for patients with all-stage melanoma showed a significantly lower risk of colitis in anti-PD1 compared with anti-CTLA4 treated patients based on log-rank test ( p = 0.017) and logistic regression (OR = 0.21, 95%CI 0.09–0.53). Conclusion: Elderly with advanced melanoma treated with anti-CTLA4 or anti-PD1 had a similar risk of developing colitis. However, there was a statistically significant difference in the risk of colitis between anti-CTLA4 or anti-PD1 users among all-stage-melanoma patients. Plain Language Summary Risk of colitis (inflammation of the large intestine) in elderly patients with melanoma treated with immune-checkpoint inhibitors (a group of medications that uses the patient’s immune system to fight cancer) While the anti-cancer agents known as immune-checkpoint inhibitors have had a great impact on the treatment of melanoma, they may also have side effects. This study estimated the risk of colitis, a chronic inflammation of the colon, in elderly patients with melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) or anti-programmed cell-death 1 (anti-PD1) agents, using data from the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database. Overall, we found that the risk of colitis was not different between anti-PD1 users and anti-CTLA4 users with advanced-stage melanoma. However, after including patients across all stages of melanoma, we found a significantly lower risk of colitis with anti-PD1 compared with anti-CTLA4.

Race, Access to Care, and Outcome After Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1509-1509
Author(s):  
Erin T Alexander ◽  
Robert K Stuart ◽  
Luciano J Costa
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Access To Care ◽  
Cell Transplantation ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Log Rank Test

Abstract Abstract 1509 Background: Autologous hematopoietic stem cell transplantation (AHSCT) is an essential modality in the management of younger, newly diagnosed multiple myeloma (MM) patients. Some reports have indicated inferior survival for African-American (AA) patients following diagnosis of MM, when compared to Caucasian (Ca) patients. We hypothesized that previously claimed racial differences in outcome may reflect disparity in access to care and might be negated by timely, standard, and uniform treatment. Methods: We reviewed a mature database of MM patients undergoing AHSCT at a single institution to describe and compare overall survival from diagnosis and from transplantation in AA and Ca patients. Additionally, we described time from diagnosis to transplantation in both cohorts as an additional surrogate of access to care. Results: Between August 1996 and July 2010, 128 patients underwent a first AHSCT for MM at the institution. Fifty-three patients (41%) were AA and 75 (59%) were Ca. Median age at the time of diagnosis was 54.7 years for AA and 58.3 for Ca. Sixty-six (52%) of patients were female. One hundred twenty-six (98%) patients received conditioning chemotherapy with Melphalan 200 mg/m2. Median interval from diagnosis to transplant was 10 months (IQR 7.1–15.9) for AA and 9.2 months (IQR 6.7–15.6) for Ca (p=0.23). Median overall survival for the entire group was 63 months (95% C.I. 51–76) from time of diagnosis and 51.8 months (95% C.I. 39–63) from AHSCT. There was no difference in overall survival from time of AHSCT between AA and Ca, respectively 62.6 (95% C.I. 30.9–94.4) and 51.8 months (95% C.I. 33.5–70.3, Log-rank test P=0.76). Similarly, no significant difference was seen in overall survival from time of diagnosis between AA and Ca, respectively 70.4 (95% C.I. 29.6–111.3) and 59.3 months (95% C.I. 46.8–71.8), as displayed in the Figure (Log-rank test P=0.36). Conclusion: These findings suggest that previously reported differences in outcome between AA and CA patients with MM are related to disparities in access to healthcare and not intrinsic biological differences. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1464
Author(s):  
Angelica D’Aiello ◽  
Juan Lin ◽  
Rasim Gucalp ◽  
Vafa Tabatabaie ◽  
Haiying Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Thyroid Dysfunction ◽  
Cox Regression ◽  
Clinical Symptoms ◽  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Lung Cancer Patients ◽  
Log Rank Test ◽  
Treatment Type

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p = 0.81 and p = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test (p = 0.016) and multivariate Cox regression (HR 0.48, p = 0.09 for White and HR 0.36, p = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test (p = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study.

Colorectal Liver Metastases - Does the Number of Lesions Determine the Sensibility of Resection?

Swiss Surgery ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 6-10
Author(s):  
Knoefel ◽  
Brunken ◽  
Neumann ◽  
Gundlach ◽  
Rogiers ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Chirurgische Entfernung

Die komplette chirurgische Entfernung von Lebermetastasen bietet Patienten nach kolorektalem Karzinom die einzige kurative Chance. Es gibt jedoch eine, anscheinend unbegrenzte, Anzahl an Parametern, die die Prognose dieser Patienten bestimmen und damit den Sinn dieser Therapie vorhersagen können. Zu den am häufigsten diskutierten und am einfachsten zu bestimmenden Parametern gehört die Anzahl der Metastasen. Ziel dieser Studie war es daher die Wertigkeit dieses Parameters in der Literatur zu reflektieren und unsere eigenen Patientendaten zu evaluieren. Insgesamt konnte von 302 Patienten ein komplettes Follow-up erhoben werden. Die gebildeten Patientengruppen wurden mit Hilfe einer Kaplan Meier Analyse und konsekutivem log rank Test untersucht. Die Literatur wurde bis Dezember 1998 revidiert. Die Anzahl der Metastasen bestätigte sich als ein prognostisches Kriterium. Lagen drei oder mehr Metastasen vor, so war nicht nur die Wahrscheinlichkeit einer R0 Resektion deutlich geringer (17.8% versus 67.2%) sondern auch das Überleben der Patienten nach einer R0 Resektion tendenziell unwahrscheinlicher. Das 5-Jahres Überleben betrug bei > 2 Metastasen 9% bei > 2 Metastasen 36%. Das 10-Jahres Überleben beträgt bislang bei > 2 Metastasen 0% bei > 2 Metastasen 18% (p < 0.07). Die Anzahl der Metastasen spielt in der Prognose der Patienten mit kolorektalen Lebermetastasen eine Rolle. Selbst bei mehr als vier Metastasen ist jedoch gelegentlich eine R0 Resektion möglich. In diesen Fällen kann der Patient auch langfristig von einer Operation profitieren. Das wichtigere Kriterium einer onkologisch sinnvollen Resektabilität ist die Frage ob technisch und funktionell eine R0 Resektion durchführbar ist. Ist das der Fall, so sollte auch einem Patienten mit mehreren Metastasen die einzige kurative Chance einer Resektion nicht vorenthalten bleiben.

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