Denis Soulieres

Centre hospitalier de l'Université de Montréal (CHUM) and Université de Montréal · Hematology and Medical Oncology

Background Adults with sickle cell disease (SCD) are at higher risk of cognitive disorder compared to the general population. The American Society of Hematology recommends cognitive screening; however, optimal surveillance strategies have not been established. The Rowland Universal Dementia Assessment Scale (RUDAS) is a short questionnaire that was...

Introduction: The management of acute moderate to severe pain episodes (APE) in patients with sickle cell disease (SCD) involves the rapid administration of opioid analgesia within 60 minutes of presentation, as recommended by the National Heart, Lung, and Blood Institute, and the American Society of Hematology. Intranasal fentanyl (INF) is therefo...

Background Pembro improved OS over SOC in patients (pts) with previously treated R/M HNSCC in the phase III KEYNOTE-040 study (NCT02252042). We present the associated exploratory biomarker results including TMB, PD-L1 CPS, and T-cell–inflamed gene signature (TcellinfGEP). Methods Pts with HNSCC who progressed during or after platinum-containing th...

Optimal targets for red blood cell exchange (RCE) are not well defined in the chronic management of sickle cell disease. We analysed transfusion requirements and iron‐related outcomes in 101 patients on chronic RCE with a post‐procedure haematocrit (Ht) targeted at 34%, which is higher than typically used. A majority were of HbSS/HbSβ0 genotype (n...

Abstract Introduction Cisplatin-associated acute kidney injury (C-AKI) is common. Predictive factors include age >60 years, hypertension, cisplatin dose, diabetes, and serum albumin < 3.5 g/L. The association between C-AKI and hypokalemia, hypomagnesemia or hyponatremia has not been well characterized. Methods Data from a previous retrospective obs...

4505 Background: P + A improved OS, PFS, and ORR over S in 1L advanced RCC in KEYNOTE-426 (NCT02853331).Here, we present exploratory biomarker results including RNAseq, WES, and PD-L1. Methods: Patients (pts) with treatment-naive advanced RCC were randomly assigned 1:1 to P + A or S. Association between T-cell–inflamed gene signature (Tcell inf GEP...

Introduction: The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, particularly among younger populations. It is projected that the number of new cases will increase by almost 50% by 2040, with market revenues expected to triple in the same period. Despite the recent introduction of immune checkpoint inhibitors (ICIs) into...

367 Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) and response rates compared to sunitinib in the pivotal Checkmate 214 trial of intermediate/poor risk mRCC. A subgroup analysis showed no significant difference in OS for ipi/nivo in pts 65 to 75 years old (yo), as well as pts >75 yo. In another subgroup analysis, Ka...

393 Background: First-line treatment for mRCC includes I/N and A/P. These two regimens have not been compared in a randomized clinical trial as both CM-214 and KN-426 used single-agent tyrosine kinase inhibitors (TKIs) as the comparator. Meta-analyses suggest improved efficacy outcomes with A/P, but increased likelihood of complete response with I/...

382 Background: The landscape of management of advanced renal cell carcinoma (aRCC) in the first line setting has changed dramatically over the past decade. Axitinib with Pembrolizumab (AP) is one of the combinations which demonstrated improved outcomes in the KEYNOTE 426 study. We report real-world outcomes and safety with this combination. Method...

366 Background: There is a paucity of data with respect to optimal management of metastatic renal cell carcinoma (mRCC) in older adults. Real world data may help close this knowledge gap and improve care for older patients with mRCC. Methods: The Canadian Kidney Cancer information system (CKCis) was utilized to identify patients with mRCC, categori...

PURPOSE Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS We included patients with mRCC enrolled in the Canadia...

Previous analyses of KEYNOTE-426, an open-label, phase 3 randomized study, showed superior efficacy of first-line pembrolizumab plus axitinib to sunitinib in advanced clear cell renal cell carcinoma (ccRCC). We report results of the final protocol-prespecified analysis of KEYNOTE-426. Patients received pembrolizumab 200 mg intravenously every 3 wk...

Objectives: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. Material and methods: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and...

Background: Although metastatic germ cell tumor (GCT) is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remain lacking. We aimed to characterize the contemporary practice patterns of salv...

LBA4501 Background: At the first interim analysis of the randomized, open-label, phase 3 KEYNOTE-426 (NCT02853331) study, 1L pembro + axi showed statistically significant OS, PFS, and ORR over sun for advanced ccRCC. We report results with 5-y minimum follow-up. Methods: Adults with confirmed locally advanced or metastatic ccRCC with or without sar...

e18030 Background: Previous analysis of the BERIL-1 Phase 2 clinical trial (Soulieres et al, CCR, 2018), evaluating the efficacy of Buparlisib + Paclitaxel, was one of the largest genomic landscape analyses to date in metastatic SCCHN. With the recent approval of PD-1 in this indication, we sought to expand the analysis, focusing on combinatorial b...

6050 Background: Anti-PD-1/PD-L1 is now part of first line therapy in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic radiotherapy (SBRT) to metastatic lesions can reduce tumor burden and could be immune-stimulatory. The combination of SBRT with dual-checkpoint blockade with Durvalumab (D, anti-PD-L1) and Tremelimumab (T, ant...

Background: Although metastatic GCT is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remains lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Cana...

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document...

Importance: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Objective: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. Design, setting, and participants: The CheckMate 7...

Background: Although metastatic germ cell tumor (GCT) is highly curable with initial 19 cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conven-20 tional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remains 21 lacking. We aimed to characterize the contemporary practice patter...

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD...

Background Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra‐cranial imaging for the screening of asymptomatic BM in mRCC. Aims To evaluate the potential utility of routine intra‐cr...

Background: Patients with sickle cell disease (SCD) are considered at higher risk of severe COVID-19 infection. However, morbidity and mortality rates are variable among countries. To date, there are no published reports that document outcomes of SCD patients with COVID-19 in Canada. Methods: A web-based registry was implemented in June 2020 cap...

Numb chin syndrome (NCS) is a rare sensory neuropathy resulting from inferior alveolar or mental nerve injury. It manifests as hypoesthesia, paraesthesia, or, rarely, as pain in the chin and lower lip. Several case reports suggest that sickle cell disease (SCD) could be a cause of NCS. However, information about NCS is scarce in this population. Ou...

Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-...

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in most head and neck squamous cell carcinomas, making it a prized target for targeted therapy development. Multiple PI3K inhibitors have been studied in early phase trials, with unfavorable risk-benefit ratios in molecularly unselected patient populations. Buparlisib, a potent pa...

Introduction: The substitution of glutamic acid by valine on the ß-globin gene produces the hemoglobin S variant responsible for sickle cell disease (SCD), a disorder that affects millions of people worldwide and leads to acute and cumulative organ damage. Even though life expectancy has significantly improved where the best medical care is availa...

Background In the phase 3 KEYNOTE-426 (NCT02853331) trial, pembrolizumab + axitinib demonstrated improvement in overall survival, progression-free survival, and objective response rate over sunitinib monotherapy for advanced renal cell carcinoma (RCC). Objective To evaluate health-related quality of life (HRQoL) in KEYNOTE-426. Design, setting, a...

Background Renal cell carcinoma (RCC) is a common malignancy with approximately 30% of cases diagnosed at the advanced or metastatic stage. While single-agent vascular endothelial growth factor-targeted therapy has been a mainstay of treatment, data from multiple phase III trials assessing first-line immune checkpoint inhibitor (ICI) combinations h...

4513 Background: The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331) met its primary and key secondary end points of improved OS, PFS, and ORR with pembro + axi versus sunitinib as first-line treatment for patients with advanced ccRCC. Extended follow-up (42.8-mo median follow-up) continued to show the superior efficacy of pembro +...

e24105 Background: Cisplatin-associated acute kidney injury (C-AKI) is common. Predictive factors of C-AKI include age > 60 years, hypertension, cisplatin dose, diabetes, and serum albumin < 3.5g/L. The association between C-AKI and hypokalemia, hypomagnesemia or hyponatremia has not been well characterized to date. Methods: Data from a previous re...

Objectives To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031). Materials and Methods HRQoL was measured using the European Organisation for Re...

PURPOSE The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031 ) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To...

Patients with sickle cell disease (SCD) who undergo repeated blood transfusions often develop iron overload. Deferiprone (Ferriprox®) is an oral iron chelator indicated for the treatment of transfusional iron overload due to thalassemia syndromes and has been recently approved as a treatment for iron overload in adult and pediatric patients with SC...

304 Background: Current treatment principles for advanced nccRCC have been largely extrapolated from guidelines for clear cell RCC. Given the emerging randomized data for select nccRCC subtypes, real-world outcomes for these patients are informative particularly in the contemporary checkpoint inhibitor era. Methods: We performed an analysis using t...

316 Background: Cabozantinib (cabo) is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in mRCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. We explored whether cabo dose reductions (a surrogate for toxicity) were associated with im...

361 Background: Characteristics of patients with high risk for recurrence non-metastatic renal cell carcinoma (nmRCC) participating in adjuvant therapy clinical trials post-nephrectomy have not been well described. We evaluated high risk nmRCC patients in the CKCis database to explore differences between trial and non-trial patients. Methods: Adult...

Introduction: We aimed to investigate several clinical and biochemical parameters, including palliative external beam radiation therapy (EBRT) to predict survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). Methods: We tested known and possible prognostic parameters, including palliativ...

Background: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the imp...

Purpose With the integration of immuno-oncology agents (IO) in the management of metastatic renal cell carcinoma (mRCC), there has been interest in the combined use with radiotherapy (RT). However, real world data is limited. The purpose of this study was to evaluate outcomes in mRCC patients receiving both RT and IO compared to IO alone. Methods...

Introduction : Ipilimumab plus nivolumab was associated with a survival benefit in a phase III clinical trial of first-line treatment for metastatic renal cell carcinoma (mRCC). In this study, mRCC patients from the Canadian Kidney Cancer Information System (CKCis) database who received first-line ipilimumab plus nivolumab were analyzed to determin...

Introduction: Sickle cell disease(SCD) is the most common genetic disease globally. It is an autosomal recessive disease that affects the β-globin chain which most often presents with anemia and vaso-occlusive symptoms. This condition includes multiples genotypes/phenotypes, the most common of which is HbSS (homozygosity for Hemoglobin S); others a...

Introduction: Numb Chin Syndrome (NCS) is a rare sensory neuropathy characterized by inferior alveolar or mental nerve damage. It manifests as hypoesthesia, paraesthesia, or pain in the chin and lower lip. Few case reports have been published on NCS secondary to sickle cell disease (SCD). As a result, information about causes, disease course and tr...

Introduction Approximately 1500 people live with sickle cell disease (SCD) in the province of Quebec, Canada. Public health has recognized these patients as immunocompromised. SCD patients may be at higher risk of developing severe COVID-19 infection due to their underlying pro-inflammatory and thrombogenic state, splenic dysfunction and secondary...

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia where blasts present phenotypes from more than one lineage. A poor prognostic has been associated with this disease, and limited data are currently available to guide the choice of therapy. Regarding FLT3‐positive MPAL, only one case treated with midostaurin has been published t...

Background Pembrolizumab plus axitinib improved efficacy over sunitinib in treatment-naive advanced renal cell carcinoma in the KEYNOTE-426 (NCT02853331) study. However, a relatively high incidence of grade 3/4 aminotransferase elevations was observed. Objective To further characterize treatment-emergent aminotransferase elevations in patients tre...

Purpose R2* relaxometry is a quantitative method for assessment of iron overload. The purpose is to analyze the cross-sectional relationships between R2* in organs across patients with primary and secondary iron overload. Secondary analyses were conducted to analyze R2* according to treatment regimen. Methods This is a retrospective, cross-section...

TPS6090 Background: Buparlisib (AN2025) is a 2,6-dimorpholino pyrimidine derivative oral pan-class I PI3K inhibitor. The PI3K signaling pathway is one of the most frequently altered pathways in HNSCC. A previous randomized, double-blind, placebo-controlled phase II study (BERIL-1) assessed patients with recurrent/metastatic HNSCC after PD on or aft...

4500 Background: In the first interim analysis of the randomized, multicenter, open-label, phase 3 KEYNOTE-426 study (NCT02853331), treatment with pembro + axi significantly improved OS, PFS, and ORR vs sunitinib monotherapy in treatment-naive advanced ccRCC. Extended follow-up (median, 30.6 mo) continued to demonstrate the superior efficacy of pem...

Importance Adults with sickle cell disease (SCD) disproportionally experience early cognitive decline; however, guidance on the optimal screening strategy for cognitive dysfunction is lacking, and several available tools are biased by language, educational level, socioeconomic status, and race/ethnicity. The Rowland Universal Dementia Assessment Sc...

Background: Active surveillance (AS) is a commonly used strategy in patients with slow-growing disease. We aimed to assess the outcomes and safety of AS in patients with metastatic renal cell carcinoma (mRCC). Patients and methods: We used the Canadian Kidney Cancer information system (CKCis) to identify patients with mRCC diagnosed between Janu...

Purpose Acute kidney injury (AKI) is a frequent dose-limiting toxicity induced by cisplatin. Mannitol has been used in hydration protocols to mitigate this adverse event but its role remains controversial. The aim of this study is to define the impact of mannitol on AKI in patients receiving cisplatin. Methods This retrospective observational stud...

Objective: To evaluate the role of incomplete metastasectomy (IM) for patients with metastatic renal cell carcinoma (mRCC) on overall survival (OS) and time to introduction of first-line systemic therapy. Methodology: Patients diagnosed with mRCC between Jan 2011 and Apr 2019 in 16 centers were selected from the Canadian Kidney Cancer information s...

Advanced RCC has seen many treatment advances in the past several years, with the introduction of many novel therapies. Recent evidence from the KEYNOTE 426 and CheckMate 214 studies, and now the addition of the CheckMate 9ER and CLEAR studies, has mandated a rearrangement of treatment algorithms for advanced clear-cell RCC with the use of doublet...

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a...

Background: Fluoropyrimidines are used in chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. DPYD*2A polymorphism is one of the most studied variants. The study objective was to document the impact of implementing this test in routine clinical practice....

Tumor proportion score (TPS) and combined positive score ([CPS] includes immune cells), 2 methods for scoring programmed death ligand 1 (PD-L1) expression, have been used in clinical trials investigating the immune checkpoint inhibitor pembrolizumab in head and neck squamous cell carcinoma (HNSCC). These trials resulted in regulatory approval for p...

Background: Cognitive impairment is a dreaded complication of sickle cell disease (SCD) that impacts quality of life, school performance and employment. In 2020, the American Society of Hematology issued a strong recommendation that clinicians supervising the care of adults with SCD conduct surveillance for cognitive impairment using simplified sig...

Background The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitin...