Publications by authors named "Kuruvilla J"

Context: Hematological malignancies represent a heterogeneous group of diseases with variable and often unpredictable illness trajectories. Comparisons between hematological and solid tumor malignancy referrals to an outpatient palliative care clinic have not been explored.

Objectives: This study compared characteristics, referral trends, and time from first palliative care clinic visit to death between patients with hematological and solid tumor malignancies.

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Background: Novel systemic anticancer therapies (SACT) in the form of targeted and immunotherapies are increasingly replacing traditional chemotherapy. Little is known about the impact of novel SACT on healthcare resource utilization (HCRU) at the end of life.

Methodology: A retrospective review of patients attending a tertiary cancer center in Toronto, Canada, with advanced solid or hematological malignancies who died in 2019.

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Article Synopsis
  • Mosunetuzumab is a bispecific antibody that targets T cells to kill malignant B cells, showing promising results in a study of patients with relapsed/refractory follicular lymphoma (FL) over 37.4 months.
  • In the study involving 90 patients, the complete response rate was 60.0%, while the objective response rate reached 77.8%, with significant durations of response reported.
  • Safety concerns were minimal, with no serious adverse events noted, indicating that mosunetuzumab could be a safe and effective outpatient treatment option for FL patients, including those with high-risk conditions.
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In the LY.17 randomized phase II clinical trial, adults with relapsed and refractory diffuse large B-cell lymphoma treated with ibrutinib-R-GDP (IR-GDP) for up to three cycles had more documented bacterial and fungal infections, without improvement in overall response, compared with R-GDP. CR, complete response; DLBCL, diffuse large B-cell lymphoma; PD, progressive disease; PR, partial response; R/R, relapsed/refractory; SD, stable disease.

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CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy has transformed the management of relapsed/refractory (R/R) large B cell lymphoma (LBCL). Initially approved in the third line and beyond setting, CAR-T is now standard of care (SOC) for second-line treatment in patients with refractory disease or early relapse (progression within 12 months) following primary chemoimmunotherapy. Despite becoming SOC, most patients do not achieve complete response, and long-term cure is only observed in approximately 40% of patients.

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Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes.

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Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2.

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Article Synopsis
  • Follicular lymphoma (FL) is the most common type of indolent B-cell non-Hodgkin lymphoma, making up about one-third of all NHL cases, and is considered incurable despite advancements in treatment over the past decade.
  • Hematopoietic cell transplantation (HCT) might be curative for some patients, while chimeric antigen receptor T-cell therapy (CAR-T) shows promising response rates in relapsed/refractory cases, but more research is needed for definitive conclusions on its curative potential.
  • The American Society of Transplantation and Cellular Therapy (ASTCT) developed 15 consensus statements to provide guidance on the use of HCT and cellular therapies in managing FL,
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Introduction: Despite clear advancements in the management of classical Hodgkin lymphoma (cHL) over the past decade including better risk stratification, the usage of 18F-flurodeoxyglucose positron emission tomography (FDG-PET)-guided approaches and incorporation of novel agents, approximately one-third of the patients will relapse. Important themes have been recently explored in the first salvage setting including the recognition of the positive prognostic value of a negative pre-autologous stem cell transplantation (ASCT) FDG-PET response and the incorporation of novel agents such as brentuximab vedotin (BV) and immune checkpoint inhibitors (CPIs) as salvage regimens to improve patient outcomes.

Areas Covered: The evolving treatment paradigm in optimizing salvage therapy in relapsed refractory cHL (RR-cHL) is discussed, including a vision to the future.

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Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins.

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An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product.

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The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.

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Chimeric antigen receptor T cell (CAR-T) therapies targeting the CD19 antigen have been associated with high and durable response rates in patients with diffuse large B cell lymphoma (DLBCL). CAR-T cell therapies are commonly administered in the inpatient setting due to the average onset of cytokine release syndrome within the first 3 days post infusion, but there has been growing interest in delivering CAR-T cell therapies in the outpatient setting to overcome frequent hospital bed shortages and the high cost of inpatient care. Although this approach could improve access whilst catering to patient preference, it requires a multidisciplinary approach as well as careful patient selection.

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Article Synopsis
  • Metabolic tumor volume (MTV), measured via PET scans, is a potential indicator of prognosis in large B-cell lymphoma (LBCL) patients, particularly in assessing how tumor burden affects treatment outcomes.
  • The ZUMA-7 study compared outcomes between patients receiving axicabtagene ciloleucel (axi-cel) and standard care, revealing that those with lower MTV (median or less) generally had better event-free survival (EFS) and progression-free survival (PFS) across both treatments.
  • Patients with high MTV showed poorer survival rates and more severe side effects, emphasizing the need for assessing MTV as a predictor of treatment response in future LBCL therapies.
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Article Synopsis
  • This study evaluated the effectiveness of ultra-low-dose chest CT (uLDCT) compared to standard low-dose chest CT (LDCT) in detecting fungal infections in immunocompromised patients.
  • One hundred patients underwent both types of scans, and three radiologists assessed the image quality and confidence in finding major and minor fungal infection signs.
  • The results showed uLDCT achieved high accuracy for detecting fungal disease, notably with an effective dose significantly lower (one quarter) than LDCT, making it a viable option for patients with a BMI under 30.
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Background: No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.

Methods: A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations.

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Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020.

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Background: Very late relapse (VLR) occurring >5 years after initial diagnosis is an uncommon event in the management of Hodgkin lymphoma (HL). Limited information regarding risk factors and optimal therapy is available.

Patients And Methods: We reviewed patients treated for HL at Princess Margaret Cancer Centre, Toronto, Ontario Canada between January 01, 1999 and 31 December 31, 2018.

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The optimal salvage chemotherapy regimen (SC) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant remains unclear. Moreover, although chimeric antigen receptor T cell (CAR-T) therapies were recently approved for primary refractory DLBCL, head-to-head comparisons are lacking. We searched MEDLINE, EMBASE and CENTRAL to July 2022, for randomized trials that enrolled adult patients with R/R DLBCL and performed network meta-analyses (NMA) to assess the efficacy of SC and CAR-T therapies.

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Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ∼5 years). Patients with R/R cHL who were brentuximab vedotin (BV)-naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity.

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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 salvage CT across Canada.

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Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV) showed promising early efficacy in patients with R/R PMBL in the phase 1/2 open-label, multicenter CheckMate 436 study; we report safety and efficacy findings from the 3-year follow-up. Patients who were eligible were aged ≥15 years with R/R PMBL previously treated with either high-dose chemotherapy plus autologous hematopoietic cell transplantation (HCT) or ≥2 prior multiagent chemotherapies, and had Eastern Cooperative Oncology Group performance status scores of 0 to 1 and CD30 expression of ≥1%.

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