In this PACUPod episode, we examine the MonumenTAL-1 Phase 2 study of talquetamab in relapsed or refractory multiple myeloma (RRMM). Using patient-reported outcomes collected with EORTC QLQ-C30, EQ-5D-5L, and PGIS, the study shows transient symptom worsening in cycle 1 followed by clinically meaningful improvements through cycle 21, including enhancements in global health status and emotional functioning, with notable reductions in pain and fatigue. We discuss the patient population (triple-class exposed RRMM with high-risk cytogenetics and extramedullary disease), dosing (0.8 mg/kg every other week), and the single-arm design, along with safety considerations (early but manageable cytokine release syndrome and skin/oral toxicities). Limitations such as open-label design and small sample size are considered, as are clinical implications for integrating PROs into routine care and real-world practice. The episode highlights how improved patient-reported outcomes can complement disease control in a challenging patient group.

This PACULit episode reviews a Phase III, triple-blinded, placebo-controlled randomized trial evaluating photobiomodulation (PBM) to prevent chemotherapy-induced dysgeusia in breast cancer patients receiving doxorubicin-cyclophosphamide (AC). Three arms compare combined red plus infrared PBM versus red-only with infrared placebo and infrared-only with red placebo, aiming to isolate the additive effect of the combined wavelengths. Primary outcome is objective taste function; secondary outcomes include subjective taste measures, quality of life (OHIP-14), ECOG performance status, BMI, salivary flow, and safety. Findings indicate that the combined red+infrared PBM better preserves objective taste, maintains salivary flow, and improves ECOG status and weight compared with single-wavelength PBM, while infrared-alone is associated with worse subjective outcomes. The intervention was safe with no excess adverse events, supporting PBM as a non-pharmacologic supportive care option to mitigate taste alterations during AC chemotherapy. Future multicenter studies and parameter optimization are warranted to extend these findings to other regimens and cancer populations.

This episode reviews Sachanas et al.'s retrospective case series of five patients with B-cell prolymphocytic leukemia (B-PLL) who presented with massive splenomegaly and prolymphocytosis but whose bone marrow and immunophenotyping were consistent with splenic marginal zone lymphoma (SMZL). The study notes absence of MYC rearrangements or TP53 deletions (one patient had a 7q31 deletion), supporting reclassification of these cases as SMZL variants with prolymphocytic morphology rather than classical B-PLL. Rituximab monotherapy, aligned with SMZL treatment, achieved complete remission in 40% and prolonged responses in 80%, suggesting a safer, well-tolerated option for elderly or frail patients who may not tolerate aggressive chemotherapy. The episode highlights diagnostic challenges and emphasizes comprehensive workup—bone marrow biopsy, immunophenotyping, and cytogenetics—to distinguish SMZL-like prolymphocytic cases from true B-PLL, guiding prognosis and therapy. It discusses limitations such as small sample size and retrospective design, and explores future directions including molecular profiling via next-generation sequencing, routine cytogenetic screening in ambiguous B-cell neoplasms, maintenance Rituximab, and potential integration with targeted therapies (BTK inhibitors, BCL2 antagonists). The takeaway is a move toward precision medicine and personalized, less toxic treatment strategies, with multidisciplinary collaboration essential for optimal care.

This PACUPod episode explores Schlueter et al.’s retrospective cohort study on a single fixed 4.5 mg intravenous dose of rasburicase for tumor lysis syndrome (TLS)–related hyperuricemia. Patients were stratified by baseline uric acid into moderate (12 to <15 mg/dL) and high (≥15 mg/dL) groups. The findings show rapid uric acid reduction in both groups, with no significant difference in clinical outcomes, suggesting that a fixed-dose approach could simplify dosing, reduce costs, and expand access—especially in resource-limited settings. The discussion covers the study’s real-world design, lack of a comparator, and limitations, while highlighting safety considerations (G6PD deficiency screening), the need for careful monitoring of renal function and electrolytes, and the potential interference of rasburicase with uric acid assays requiring prompt processing. Practical implications include early intervention, streamlined pharmacy workflow, and potential guideline integration; the episode also notes that most patients did not require repeat dosing and calls for prospective trials comparing fixed-dose versus weight-based regimens to assess long-term renal outcomes and cost-effectiveness.

In this episode, Britany and Seth discuss Sachanas et al.'s retrospective case series of five patients with massive splenomegaly and prolymphocytosis who clinically resembled splenic marginal zone lymphoma (SMZL) but fulfilled criteria for B-cell prolymphocytic leukemia (B-PLL). Despite >55% circulating prolymphocytes, bone marrow infiltration and immunophenotyping were SMZL-like. No MYC rearrangements or TP53 deletions were found; one patient exhibited a 7q31 deletion, supporting SMZL-variant classification. Rituximab monotherapy yielded a complete remission rate of 40% and prolonged responses in 80%, suggesting potential for less toxic, effective therapy in elderly or frail patients. The discussion covers diagnostic challenges, the risk of misclassification, and treatment implications, emphasizing comprehensive workups (morphology, immunophenotyping, cytogenetics) and multidisciplinary care. Limitations include small sample size and retrospective design; future directions include molecular profiling, routine cytogenetic screening, prospective trials, maintenance Rituximab, and exploration of targeted therapy combinations.

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"episode_description": "PACULit Daily Literature Update: Today we review a Phase 1b2 open-label multicenter trial evaluating cavrotolimod, a TLR9 agonist, in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab) for advanced cutaneous malignancies, including melanoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma. The study (NCT03684785) enrolled 58 adults with heavily pre-treated disease, beginning with cavrotolimod monotherapy dose escalation followed by combination therapy. Primary endpoints focused on safety and tolerability; secondary endpoints assessed objective response rate (ORR), disease control rate (DCR), and duration of response, along with pharmacokinetics, pharmacodynamics, and immune biomarkers. Among 51 evaluable patients, ORR was 12% (6/51) and DCR was 27% (14/51) with median duration of response of 54 weeks; regression occurred in both injected and distant lesions, indicating an abscopal effect. Safety was manageable, with fatigue and injection-site reactions being the most common grade 3/4 events. Immune profiling showed robust peripheral cytokine/chemokine induction and increased tumor immune cell infiltration, suggesting synergy between cavrotolimod and anti-PD-1 therapy. While promising in a refractory population, limitations include the single-arm design and small, heterogeneous cohort. Full study details are reported by Milhem et al., 2025 in the Journal for Immunotherapy of Cancer, and ongoing trials will clarify potential clinical benefit of this approach for resistant skin cancers.",

"keywords": [

"TLR9 agonist",

"cavrotolimod",

"intratumoral administration",

"anti-PD-1 therapy",

"pembrolizumab",

"cemiplimab",

"Phase 1b2",

"open-label",

"multicenter",

"cutaneous malignancies",

"melanoma",

"Merkel cell carcinoma",

"cutaneous squamous cell carcinoma",

"refractory to anti-PD-(L)1",

"safety and tolerability",

"

Welcome back to PACULit, your daily literature update for clinical pharmacists and physicians. Today we review a Phase III, triple-blind, placebo-controlled randomized trial evaluating photobiomodulation (PBM) to prevent chemotherapy-induced dysgeusia in breast cancer patients receiving doxorubicin–cyclophosphamide. The study directly compares a combined red plus infrared PBM protocol against single-wavelength PBM (red only or infrared only) to isolate each wavelength’s contribution. Primary endpoint was objective taste function; secondary endpoints included subjective taste measures, quality of life, salivary flow, ECOG status, BMI/weight, and safety. Enrolling 180 patients across three arms, the results showed that the combination of red and infrared PBM best preserved objective taste and yielded the most favorable ECOG improvements and weight trends, with salivary flow maintained and no increase in adverse events. By contrast, red-light alone led to objective taste decline, while infrared alone produced worse subjective taste outcomes, suggesting a synergistic effect when both wavelengths are used together. Contextualized with prior Phase II findings and WALT recommendations, these results strengthen PBM as a non-pharmacologic supportive care option to mitigate chemo-induced dysgeusia, though limitations include single-center design and short-term follow-up, with no dose–response exploration. The authors call for multicenter trials across other regimens and cancers, and potential integration with nutrition and oral health interventions. Clinicians should consider proactive taste assessment in patients on anthracyclines and discuss combined PBM as a preventive strategy where feasible. DOI: 10.1007/s00520-025-09756-4.

A concise overview of the first-in-human study of a no-alpha interleukin-2 (IL-2) mutein in patients with advanced solid tumors. The episode covers the rationale for avoiding IL-2 receptor alpha (CD25) to spare regulatory T cells, the phase I dose-escalation design, safety and pharmacodynamic findings showing selective activation of CD8+ T cells and NK cells, and the preliminary clinical signals. We discuss the implications for pharmacists and physicians, including dosing considerations, safety monitoring, and future study directions, with attention to limitations such as small sample size and lack of a control arm.

This episode reviews the COAST trial, which evaluated durvalumab alone or in combination with two novel immunomodulators—oleclumab (anti-CD73) and monalizumab (anti-NKG2A)—as consolidation therapy after platinum-based concurrent chemoradiotherapy in unresectable stage III NSCLC. In this phase 2, open-label, randomized study (n=186), patients with ECOG 0–1 were assigned to durvalumab alone, durvalumab plus oleclumab, or durvalumab plus monalizumab for up to 12 months. The primary endpoint was confirmed objective response rate; secondary endpoints included progression-free survival, overall survival, and safety. Results showed higher objective response rates with the combinations (durvalumab alone 23.9%; with oleclumab 35.0%; with monalizumab 40.3%), and significant improvements in progression-free survival for both combination arms (hazard ratios ~0.59 and ~0.63, respectively) compared with durvalumab alone. No OS improvement was observed yet, consistent with the phase 2 design and limited follow-up. Safety profiles were similar across arms, with immune-related events aligning with known durvalumab toxicities and no major increases in toxicity from adding oleclumab or monalizumab. Mechanistically, oleclumab reduces adenosine-mediated immunosuppression by blocking CD73, while monalizumab relieves NKG2A-mediated inhibition of NK and CD8+ T cells, theoretically enhancing PD-L1 blockade efficacy. Clinicians should note the selective eligibility (post-cCRT, ECOG 0–1) and ongoing need for phase 3 confirmation (PACIFIC-9) to determine OS benefit and potential shifts in standard of care. Practical takeaways include vigilant monitoring for immune-related adverse events, adherence to durvalumab consolidation, and awareness of potential overlapping toxicities. The COAST data are encouraging but require further validation before changing practice.