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Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma., Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study. Talquetamab at a dose of 0.8 mg per kilogram of body weight plus teclistamab at a dose of 3.0 mg per kilogram every other week was selected as the recommended phase 2 regimen. The primary objective was to evaluate adverse events and dose-limiting toxic effects., Results: A total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months. Three patients had dose-limiting toxic effects (including grade 4 thrombocytopenia in 1 patient with the recommended phase 2 regimen). Across all dose levels, the most common adverse events were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of the patients. Grade 3 or 4 infections occurred in 64% of the patients. With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease); across all dose levels, a response occurred in 78%. The likelihood of patients continuing in response at 18 months was 86% with the recommended phase 2 regimen (82% among those with extramedullary disease) and 77% across all dose levels., Conclusions: The incidence of grade 3 or 4 infections with talquetamab plus teclistamab was higher than has been observed with either therapy alone. A response was observed in a high percentage of patients across all dose levels, with durable responses with the recommended phase 2 regimen. (Funded by Janssen Research and Development; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.)., (Copyright © 2025 Massachusetts Medical Society.)

Background: Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described., Discussion: GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies., Conclusion: Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence. VIDEO ABSTRACT., (Copyright © 2024. Published by Elsevier Inc.)

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393. In addition to adverse events (AEs) associated with T-cell-redirection therapies irrespective of target, a consistent pattern of dermatologic and oral AEs has been reported across several trials of GPRC5D-targeting bispecific antibodies, as well as rare cerebellar events with CAR-T therapy. Additional studies are needed to understand the underlying mechanisms involved in the development of skin- and oral-related toxicities. We review the strategies that have been used to manage these GPRC5D-related toxicities. Preliminary efficacy data showed overall response rates for GPRC5D-targeting T-cell-redirecting therapies were ≥64%; most responders achieved a very good partial response or better. Pharmacokinetics/pharmacodynamics showed that these therapies led to cytokine release and T-cell activation. In conclusion, results from early phase trials of GPRC5D-targeting T-cell-redirecting agents have shown promising efficacy and manageable safety profiles, including lower infection rates compared with B-cell maturation antigen- and Fc receptor-like protein 5-targeting bispecific antibodies. Further clinical trials, including those investigating GPRC5D-targeting T-cell-redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary., (© 2024. The Author(s).)

Introduction: The demand for cancer services is growing due to increased incidence and the number of people who survive their initial diagnosis but require ongoing therapy. One method of increasing capacity in radiation oncology is to delegate tasks from one professional group to another. In the last ten years there has been increasing interest in advanced practice radiation therapist (APRT) roles. The majority of the Australian literature relates to metropolitan radiation oncology centres with a paucity of information from regional or rural settings. This study sought to explore the knowledge of, and attitudes to APRT roles of members of three professional groups in public radiation oncology centres in Tasmania., Method: Data was collected through a self-reported online survey from radiation oncologists (RO), radiation oncology medical physicists (ROMP) and radiation therapists (RT) working in Tasmanian public radiation oncology services regarding their knowledge and understanding of APRT roles, acceptance and support for the roles and where APRTs could contribute to improving patient care. The survey incorporated a combination of five point Likert scale, Yes/No/Don't know and Yes/No/Not Applicable choices. The survey was reviewed by a professional panel of RT, RO and ROMP from mainland Australian radiation oncology centres., Results: At the time of survey invitation, there were 52 RTs, 7 ROs, and 7 ROMPs working in the identified departments. The survey had an overall response rate of 48.5%with profession specific response rates of 48.1% (RT), 42.9% (RO) and 57.1% (ROMP). General agreement was found amongst survey respondents with regards to understanding of APRT roles having themes of clinical expertise, leadership, communication, collaboration and teaching. Where participants were offered a list of tasks to choose those appropriate to APRT roles, the highest agreement was with "Contour organs at risk per protocol", "Image review - soft tissue online decision making/adaptive RT" and "Principal investigator in clinical research. The notion of establishing ARPT roles was well supported, as strong agreement was found with the statements related to improvement in job satisfaction, opportunities, recruitment and retention for RTs, and that APRTs could be used to relieve workload of other professionals., Conclusion: This exploratory study found that the respondents were generally in favour of APRT roles, but that they were not clear about the tasks to be performed by APRTs. It was identified that patients, ROs, ROMPs, RTs and the department would benefit from the implementation of APRT roles. Sseveral areas of practice were identified by respondents which they perceived would improve the quality of patient care., (Copyright © 2021. Published by Elsevier Inc.)

The purpose of this scoping review is to examine the literature regarding the development, implementation, scope and extent of Advanced Practice Radiation Therapist (APRT) roles in Australia in peer reviewed journals, government reports, conference proceedings and reports. A search was undertaken of PubMed, Web of Science and CINAHL, the ASMIRT website and, and Google Scholar to identify relevant documents. Combinations of keywords with Boolean operators ((advanced practice) OR (advanced practitioner) OR (specialist)) AND ((radiation therapist) OR (radiation therapy)) were used. Online and physical searches were conducted between July 16 and 23 2017. Results were not date limited. The searches retrieved 352 after duplicates were removed with 46 remaining after filtering for eligibility criteria. Items consisted of journal articles, conference abstracts, presentation slides, online presentations, State government and ASMIRT reports. A number of potential and existing APRT roles were found in the identified articles, including image review, stereotactic, treatment review, breast localisation, palliative radiotherapy, brachytherapy, radiation engineering and urology. Despite reports indicating that radiation therapists in Australia have been concerned with professional directions since 2001, there is little evidence of formal progress towards defined APRT roles. Several centres have implemented roles in a number of practice areas. The success of APRT roles lies in the ability to demonstrate that implementation goals have been achieved and that patient care has improved. The literature suggests that this is occurring, however, the presented evidence is not compelling., (© 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Introduction: In 2001, the Radiation Therapy Advisory Panel (RTAP) of the Australian Society of Medical Imaging and Radiation Therapy (ASMIRT) (formerly known as Australian Institute of Radiography) published a model for radiation therapist staffing in Australian radiation oncology departments. Between 2012-2013, the model was reviewed to ensure it reflected current radiation therapy practice, technology, and to facilitate forward planning of the radiation therapy workforce., Method: Twenty-four sites from all states participated and provided data on megavoltage simulation, planning and treatment delivery. For simulation and planning activity, the length of time to complete was collected against relevant Medicare Benefits Schedule (MBS) items. For treatment delivery, time to complete activities was collected against a common set of activities. Modelling assumptions are clearly identified in the methodology., Results: A new model was developed retaining the essential model parameter of full-time equivalent (FTE) radiation therapists (RTs) per linear accelerator operating hour as in the 2001 model but based on contemporary practice and data. The model also includes significant refinements that improve the model's overall utility and flexibility for both workforce planning purposes and for individual services to use the model according to their own organisational needs and service delivery profiles., Conclusion: The ASMIRT believes that the 2014 RT staffing model provides the utility and flexibility for radiation oncology services to best plan RT staffing establishments according to their needs and reflecting the diversity between services and within the sector. It should also provide a robust and valid basis for governments and service planners to use as a guide in workforce planning into the future., (© 2016 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Aims: In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites., Materials and Methods: A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale., Results: In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)