Medicine (St Vincent's) - Research Publications
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ItemElranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results(Nature Research, 2023)Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete response. Fifty responders switched to biweekly dosing, and 40 (80.0%) improved or maintained their response for ≥6 months. With a median follow-up of 14.7 months, median duration of response, progression-free survival and overall survival (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). With biweekly dosing, grade 3-4 adverse events decreased from 58.6% to 46.6%. Elranatamab induced deep and durable responses with a manageable safety profile. Switching to biweekly dosing may improve long-term safety without compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .
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ItemExecutive summary of consensus clinical practice guidelines for the prevention of infection in patients with multiple myeloma(WILEY, 2023-08)Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.
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ItemAnti-CD30 antibody-drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives.(Springer Science and Business Media LLC, 2023-01)CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody-drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years.
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ItemIsatuximab Plus Pomalidomide/Low-Dose Dexamethasone Versus Pomalidomide/Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (ICARIA-MM): Characterization of Subsequent Antimyeloma Therapies(American Society of Hematology, 2022-11-15)Introduction: Based on the primary analysis of the Phase 3 ICARIA-MM study (NCT02990338), isatuximab (Isa), an anti-CD38 monoclonal antibody, is approved in combination with pomalidomide and dexamethasone (Pd) in several countries for patients with relapsed and refractory multiple myeloma (RRMM) who have received at least 2 prior treatments, including lenalidomide and a proteasome inhibitor. Here, we describe updated, longer-term efficacy data following subsequent therapy. Methods: Patients were randomized 1:1 to Isa-Pd (n=154) or Pd (n=153), with stratification by age (<75 vs ≥75) and number of prior lines (2-3 versus more than >3). Isa 10 mg/kg was administered weekly for the first 4-week cycle and every 2 weeks thereafter. In each cycle, both treatment arms received pomalidomide 4 mg (days 1-21) and weekly dexamethasone 40 mg (days 1, 8, 15, and 22). Treatment was given until progressive disease, unacceptable adverse events, or patient choice. The final overall survival analysis was planned when 220 death events occurred. Results: As of March 14, 2022, 16 (10.4%) patients receiving Isa-Pd and 3 (2.0%) patients receiving Pd were still on treatment; 101 (65.6%) and 117 (76.5%) patients, respectively, discontinued treatment due to progressive disease. Median treatment duration was longer with Isa-Pd vs Pd (47.6 vs 24.0 weeks). After a median 52.4 months of follow-up, a clinically meaningful overall survival (OS) benefit was observed in favor of Isa-Pd vs Pd after 220 events (Jan 27, 2022; median: 24.6 vs 17.7 months; hazard ratio 0.776 [95% CI: 0.594-1.1015]; one-sided P=0.0319; significance level: P=0.02). Further antimyeloma treatment was given to 102 (66.2%) patients receiving Isa-Pd and 119 (77.8%) patients receiving Pd (regardless of the reason for treatment discontinuation in both arms), with a median of 2 and 1 further regimens, respectively. Of the patients receiving subsequent therapy, 22.5% (23/102) in the Isa-Pd arm and 59.7% (71/119) in the Pd arm received daratumumab. The most common further antimyeloma treatments for patients in the Isa-Pd arm were corticosteroids (n=88/102; 86.3%), alkylating agents (n=71/102; 69.6%), and proteasome inhibitors (n=70/102; 68.6%); the most common treatment received in the first subsequent line was a proteasome inhibitor (n=54/102; 52.9%). The most common further antimyeloma treatments for patients in the Pd arm were corticosteroids (n=94/119; 79.0%), monoclonal antibodies (n=75/119; 63.0%), and proteasome inhibitors (n=69/119; 58.0%); the most common treatment received in the first subsequent line was daratumumab (n=52/119; 43.7%). The overall response rate (ORR) for the first subsequent line of therapy was 28.8% (23/80) for the Isa-Pd arm and 35.3% (30/85) for the Pd arm. The ORR for patients receiving daratumumab-based regimens as the first subsequent line was 25.0% (2/8) for the Isa-Pd arm and 40.5% (17/42) for the Pd arm. The ORR for patients receiving daratumumab as monotherapy or with steroids in any subsequent line was 12.5% (1/8) for the Isa-Pd arm and 36.7% (11/30) for the Pd arm. The ORR for patients receiving daratumumab in combination with immunomodulatory agents, alkylating agents, or proteasome inhibitors in any subsequent line was 28.6% (4/14) for the Isa-Pd arm and 44.8% (13/29) for the Pd arm. Progression-free survival (PFS) on first subsequent line for patients receiving daratumumab was 2.2 months for the Isa-Pd arm and 5.7 months for the Pd arm. PFS on first subsequent line for patients receiving treatment excluding daratumumab was 4.6 months for the Isa-Pd arm and 5.2 months for the Pd arm. Conclusions: This analysis demonstrates that the majority of patients with RRMM require multiple lines of subsequent therapy, even after receiving a triplet combination that includes a monoclonal antibody. The immediate use of an anti-CD38 monoclonal antibody with currently available combinations appears to be less effective in the Isa-Pd arm. The more frequent use of subsequent daratumumab in Pd (59.7%) compared with Isa-Pd (22.5%) may have affected the power to detect statistically significant OS given the sample size, as well as reflecting the efficacy of this approach in the management of RRMM.
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ItemIgG4-related ophthalmic disease in association with adult-onset asthma and periocular xanthogranuloma: a case report(TAYLOR & FRANCIS INC, 2023-01-01)A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association.
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ItemCD30- positive lymphoproliferative disorders— An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre(Wiley, 2023)The CD30- positive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.
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ItemThe importance of frailty assessment in multiple myeloma: a position statement from the Myeloma Scientific Advisory Group to Myeloma Australia(WILEY, 2023-05)Multiple myeloma (MM) is a disease of older people, yet factors relating to comorbidity and frailty may threaten treatment tolerability for many of this heterogenous group. There has been increasing interest in defining specific and clinically relevant frailty assessment tools within the MM population, with the goal of using these frailty scores, not just as a prognostic instrument, but also as a predictive tool to allow for a frailty-adapted treatment approach. This paper reviews the various frailty assessment frameworks used in the evaluation of patients with MM, including the International Myeloma Working Group Frailty Index (IMWG-FI), the Mayo Frailty Index and the simplified frailty scale. While the IMWG-FI remains the most widely accepted tool, the simplified frailty scale is the most user-friendly in busy day-to-day clinics based on its ease of use. This paper summarises the recommendations from the Myeloma Scientific Advisory Group (MSAG) of Myeloma Australia, on the use of frailty assessment tools in clinical practice and proposes a frailty-stratified treatment algorithm to aid clinicians in tailoring therapy for this highly heterogeneous patient population.
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ItemNo Preview AvailableStaphylococcal toxic shock syndrome: still a problem - Comment(WILEY, 2005-06-20)
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ItemNo Preview AvailableStaphylococcal toxic shock syndrome: still a problem(Australasian Medical Publishing Company, 2005-06-20)We report a recent case of toxic shock syndrome associated with menstruation which illustrates that this syndrome still occurs, even when tampons are used appropriately. A potential diagnostic test for the syndrome is also discussed.
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ItemNo Preview AvailableCognition in healthy older women is a predictor of 14‐year falls risk(Wiley, 2021-12)Background: Falls are a significant cause of injuries, loss of confidence, increased morbidity, and institutionalisation in all older people, with women at 50% greater risk than men. The relationship between dementia and falls is well established and 2/3 of all dementia occurs in women. In this study we explored risk factors associated with a 14 year falls risk in a community-based cohort of women, which included validated measures across a wide range of clinical domains including neuropsychological, mood, quality of life and biomarkers (including hormonal). Method: The Australian Women’s Healthy Aging Project is an longitudinal observation study, assessments every year (1991 –1999), followed by assessments in 2002, 2004, 2012 and 2014. The assessments included cognitive (as of 2002), blood, and cardiovascular disease risk assessment, and questions related to falls. After data cleaning, the remaining cohort consisted of 180 participants (Table 1). Missing data were imputed using mice random forest. To identify key risk factors associated with a 14 year falls risk, random survival (time to event) forest (RSF) machine learning was used. Result: The RSF model, using all 290+ possible predictive variables, performed well with an Out Of Bag (OOB, withheld data) prediction error (C-index) of 32.8%. The most predictive variables in the model were identified using the variable importance measure (VIM). The initial model was refined by taking the top 30 predictive variables and retraining the RSF. This refined model resulted in an improved OOB C-index of 5.8% (27%). The top 20 predictive variables, Figure 1, include those associated with cardiovascular disease risk, cognitive performance, and hormone levels (e.g., family history of heart attack, digit symbol coding, and estradiol levels). Conclusion: Ninety percent of the top 20 predictive risk variables for the 14 year fall risk in women, were from three key domains, cognition (40%), cardiovascular (25%) and hormone-related measurements (25%). Our data suggest that for long term prevention of falls these domains may be important reducing risk of falls in the senior female population.