In this PACULit episode, Britany and Seth discuss a retrospective real-world study evaluating a single fixed 4.5 mg dose of rasburicase for TLS-related hyperuricemia. They explain stratification by baseline uric acid (moderate 12 to <15 mg/dL versus high ≥15 mg/dL) and report rapid uric acid reductions in both groups, with no significant differences in clinical outcomes. The discussion highlights potential cost savings, easier pharmacy workflows, and expanded access in resource-limited settings, along with safety considerations (G6PD screening, uric acid assay interference) and key limitations of retrospective data. They also outline practical takeaways and directions for future prospective trials and broader populations (pediatric and renal impairment).

In this PACULit episode, Britany and Seth discuss Sachanas et al.'s August 2025 study on B-cell prolymphocytic leukemia cases that mimic splenic marginal zone lymphoma. The hosts review how SMZL-like biology can occur within B-PLL phenotypes, evaluate Rituximab monotherapy as a safer alternative to chemotherapy or splenectomy, and emphasize the importance of comprehensive immunophenotyping and cytogenetics to guide therapy. Key findings include complete remission in 40% and prolonged responses in 80%, the relevance of 7q deletions, and the study's limitations and implications for future guidelines and personalized treatment in older or frail patients.

{

"episode_title": "PACULit Daily Literature Update: Cavrotolimod + Anti-PD-1 in Advanced Skin Cancers (Phase 1b2)",

"episode_description": "Britany and Seth review a Phase 1b2 open-label trial evaluating intratumoral cavrotolimod, a TLR9 agonist, in combination with systemic anti-PD-1 antibodies (pembrolizumab or cemiplimab) in 58 patients with advanced or metastatic melanoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma who largely progressed on prior anti-PD-(L)1 therapy. The discussion covers trial design, safety and early efficacy signals (ORR 12%, DCR 27%), durable responses, and evidence of an abscopal effect. Immune profiling showed robust innate/adaptive activation, including interferon signaling and increased tumor-infiltrating cytotoxic T cells and dendritic cells. The episode also highlights safety, pharmacodynamics, and the need for larger trials to confirm efficacy and guide patient selection.",

"study_details": {

"trial_phase": "Phase 1b2",

"trial_nct": "NCT03684785",

"design": "open-label, multicenter, dose-escalation and expansion, single-arm",

"population": [

"advanced/metastatic melanoma",

"Merkel cell carcinoma",

"cutaneous squamous cell carcinoma"

],

"number_enrolled": 58,

"evaluable_for_response": 51

},

"outcomes": {

"objective_response_rate": "12%",

"disease_control_rate": "27%",

"median_duration_of_response_weeks": 54,

"median_duration_of_stable_disease_weeks": 24,

"abscopal_effect": true

},

"safety_and_tolerability": {

"common_grade_3_4_AEs": [

"fatigue",

"injection_site_reactions"

],

"overall_tolerability": "manageable"

},

"immune_correlates": [

"increased circulating chemokines/cytokines",

"lymphocyte activation in blood",

"upregulation of interferon pathway genes in tumor",

"enhanced tumor infiltration by cytotoxic T cells and dendritic cells"

],

"mechanism_and_rationale": "TLR9 activation by cavrotolimod primes innate and adaptive immunity to overcome PD-1 blockade resistance; after

In this PACULit episode, a Western China retrospective study evaluates the real-world effectiveness of eculizumab for atypical hemolytic uremic syndrome (aHUS). The cohort (n=17) examines early versus delayed initiation (within 7 days of symptom onset) and reports substantial renal and hematologic responses with early treatment, including marked improvements in serum creatinine, eGFR, platelets, and LDH, along with reduced dialysis dependency. Early initiators showed higher renal and hematologic remission rates and better short-to-mid-term renal survival compared with delayed initiators. The discussion covers safety considerations, infection risk management, and the need for meningococcal vaccination and vigilance for non-meningococcal infections, as well as implications for practice in resource-limited settings. Limitations include small sample size and retrospective design. The findings align with guidelines supporting early complement blockade and highlight the role of multidisciplinary care and genetic testing in tailoring therapy, with notes on cost-effectiveness and future directions such as longer-acting agents and broader real-world data.

In this PACUPod overview, hosts Britany and Seth examine Wake et al.'s study on anti-angiogenic therapy for advanced hepatocellular carcinoma (HCC). They discuss how treatments like atezolizumab-bevacizumab and lenvatinib can cause non-tumoral liver volume loss, sometimes independent of tumor shrinkage, and the clinical implications for liver function monitoring, dosing decisions, and patient selection. The episode highlights practical takeaways for clinicians and pharmacists, the study's limitations, and future research directions, including potential integration of liver volumetry into routine management and the need to balance efficacy with preservation of liver reserve.

In this PACULit episode, Britany and Seth discuss the Turkish Oncology Group’s TOG study, a multicenter retrospective cohort of 153 patients with metastatic gastric or GEJ adenocarcinoma and PD-L1 CPS ≥5 treated with first-line nivolumab plus chemotherapy. The discussion covers study design, key outcomes (median PFS 11.06 months; median OS 16.03 months), and the prognostic and predictive value of baseline systemic inflammatory markers (NLR, PLR, SII). It highlights that SII and PD-L1 CPS independently predict treatment response, while NLR and PLR are significant only in univariate analyses, and notes limitations such as retrospective design and baseline-only measurements. The episode also discusses clinical implications for using SII alongside PD-L1 CPS to refine patient selection and monitoring, plus future directions like prospective dynamics, broader populations, and integration with genomic or microbiome data.

In this PACULit episode, the topic is the prospective validation of the Childhood Hodgkin International Prognostic Score (CHIPS) in high-risk pediatric Hodgkin lymphoma treated within the AHOD1331 trial. CHIPS, based on stage IV disease, large mediastinal adenopathy, hypoalbuminemia, and fever, independently predicts event-free survival across treatment arms (brentuximab vedotin plus AVEPC versus ABVE-PC) and across PET2 response categories and disease stages. CHIPS distribution was balanced between arms, supporting unbiased validation. The prognostic value persists among PET2 rapid responders and stage IVB patients, highlighting CHIPS as a practical, cost-effective tool to guide risk-adapted therapy and resource allocation, especially where advanced diagnostics are limited. Clinical implications include anticipating toxicities and informing dose-modification decisions, with attention to brentuximab vedotin–related neuropathy and other regimen toxicities. Limitations include generalizability to non-high-risk groups and the absence of novel biomarkers; integration with PET2 remains advisable for refined risk stratification. For full details, see PMID 40515508.

This PACULit episode reviews a prospective, single-center randomized controlled trial evaluating oral cryotherapy (ice or lollies) during intravenous methotrexate–based chemotherapy to prevent oral mucositis in children with hematolymphoid malignancies. Key findings show a significant reduction in oral mucositis incidence (22.2% with cryotherapy vs 63.4% with standard care; RR 0.35, p ≤ 0.001), with fewer severe cases and shorter duration, and no notable cryotherapy-related adverse events. The discussion outlines the timing, adherence considerations, and potential integration into pediatric oncology protocols as a simple, low-cost preventive strategy, alongside limitations like single-center design and moderate sample size. The episode also situates the study within broader evidence and ongoing trials in pediatric mucositis prevention, and highlights practical implications for clinical practice, including patient/caregiver education, coordination among care teams, and the role of cryotherapy within a comprehensive oral care protocol.