CONSORT flow diagram for COBALT-RCC trial design schematic

Introduction Despite advances in multiple myeloma treatment, most patients (pts) will relapse, highlighting the need for new drug classes to improve outcomes in RRMM. Further, extensive use of lenalidomide (LEN), an immunomodulatory drug (IMiD), as frontline and maintenance therapy has increased LEN refractoriness, decreasing responses to subsequent treatment. G protein-coupled receptor class C group 5 member D (GPRC5D) is a promising therapeutic target for RRMM as the receptor is highly expressed on malignant plasma cells with little to no expression in non-plasma immune cells and limited expression in healthy tissues. Arlocabtagene autoleucel (arlo-cel), a GPRC5D-directed autologous CAR T-cell therapy, has demonstrated safety and efficacy in pts with RRMM in a first-in-human phase 1 study. Following a single infusion of arlo-cel (150 × 106 CAR T cells), overall response rate (ORR) was 96% (23/24) and 91% (21/23) in those with 1-3 and ≥3 prior lines of therapy (pLOT), respectively. Objective To present the study design for QUINTESSENTIAL-2 (NCT06615479), a randomized, open-label, multicenter, phase 3 confirmatory study comparing the efficacy and safety of arlo-cel vs standard of care (SOC) in adults with RRMM. Methods Pts must be aged ≥18 years, with a confirmed MM diagnosis per International Myeloma Working Group criteria, 1-3 pLOT (may include a proteasome inhibitor, IMiD, and anti-CD38 antibody), measurable disease, and ECOG performance status 0 or 1. Pts with prior GPRC5D-targeted therapy are excluded. Eligible pts must have prior LEN exposure (with ≥2 consecutive cycles, unless best response of progressive disease to LEN-containing treatment or in cases of LEN intolerance or unacceptable toxicity) and will be randomized 1:1 to Arm A or Arm B. Arm A includes leukapheresis within 3-4 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per investigator choice within 6 days of randomization, and lymphodepleting chemotherapy prior to a single arlo-cel infusion. Arm B includes SOC of DPd or Kd per investigator choice, dosed per labeling, until disease progression. Primary endpoints are progression-free survival and minimal residual disease (MRD) negativity in complete response. Secondary endpoints include overall survival, ORR, MRD-negative status, complete response rate, time to response, duration of response, pharmacokinetics, and patient-reported quality of life outcomes. Pts will be followed for ≤5 years after the last pt is randomized, with a subsequent long-term follow-up study (≤15 years post-infusion) for pts receiving arlo-cel. Results This is a trial in progress and is expected to enroll 440 pts at ∼126 sites globally. The first pt was enrolled in March 2025. Conclusion This phase 3 study will compare the efficacy and safety of arlo-cel vs SOC in adult pts with RRMM refractory to LEN.

Summary of Treatment-Related TEAEs in Safety Analysis Set by Dose Level

BACKGROUND:We evaluated whether a daily nasal spray of interferon-alpha (IFN-α) would reduce the incidence of COVID-19 or community-acquired respiratory viral infections in adult cancer patients. METHODS:In this multicenter, randomized, double-blinded, placebo-controlled trial, participants were randomized 1:1 to receive daily 40 000 IU IFN-α nasal spray or normal saline placebo. Participants who developed influenza-like symptoms self-collected nasal swabs for PCR testing of SARS-CoV-2, influenza A/B, respiratory syncytial virus, parainfluenza, adenovirus, seasonal coronavirus, picornavirus, human metapneumovirus, and/or SARS-CoV-2 rapid antigen testing. Co-primary endpoints were incidence of COVID-19 and/or other respiratory viruses ≤90 days of randomization. RESULTS:Four hundred and thirty-three participants were randomized to IFN-α (n = 217) or placebo (n = 216). The incidence of COVID-19 was lower in the IFN-α group versus placebo (8.3% vs 14.4%), indicating a 40% reduced risk of infection (relative risk [RR]: .60; 95% credible interval [CrI]: .33-.97). Other respiratory viral infection incidence was 5.1% and 5.1% in both groups (RR: 1.12; .43-2.34). In the per-protocol cohort (n = 389), the incidence of COVID-19 in IFN-α and placebo groups was 7.7% and 16.0% (RR: .50; .26-.84) with other respiratory virus incidence of 4.6% and 5.7%, respectively. Subgroup analysis demonstrated lower COVID-19 in the IFN-α group for ages <65 years (RR: .48; .20-.92), female sex (RR: .44; .19-.85), and COVID-19 vaccinated (RR: .50; .26-.82), but no difference by underlying malignancy. No differences were observed in secondary endpoints of severity, hospitalization, and mortality. IFN-α was well tolerated and safe. CONCLUSIONS:IFN-α nasal spray prophylaxis reduced the incidence of COVID-19 among adult cancer patients. CLINICAL TRIALS REGISTRATION:ClinicalTrials.gov identifier: NCT04534725 (ANZCTR: ACTRN12620000843954).

Cytokine secretion during CAR T-cell activation upon coculture with CD70+ RCC cells

Introduction: Cilta-cel is approved in the US and the EU for the treatment of patients (pts) with lenalidomide-refractory multiple myeloma (MM) after ≥1 prior line of therapy (pLOT), including a proteasome inhibitor and an immunomodulatory agent based on the CARTITUDE-1 (CART-1, NCT03548207) and CARTITUDE-4 (CART-4, NCT04181827) studies. Cilta-cel led to deep and durable responses and significant survival benefit in pts with relapsed/refractory MM (RRMM) after ≥3 pLOT in CART-1. In CART-4, cilta-cel led to a significant overall survival benefit with a higher proportion of pts achieving deep, sustained minimal residual disease negativity vs standard of care in pts with lenalidomide-refractory MM after 1–3 pLOT. We investigated the mechanism of action of cilta-cel by correlating biomarkers from peripheral blood and the bone marrow TME with progression-free survival (PFS) and number of pLOT in pts with RRMM from CART-1 and CART-4. Methods: Biomarker analyses were performed using peripheral blood and bone marrow aspirates (BMAs) collected in both CART-1 and CART-4 studies. Immunophenotyping by flow cytometry was performed using peripheral blood at baseline/time of apheresis in samples from both studies. Immune fitness at baseline was assessed in pts by pLOT and in association with PFS. Gene set enrichment scores were derived from RNA sequencing data of the TME using BMAs. Mixed-effects models were used to identify signatures/pathways modulated over time (day [D] 28 and at 6 months [mo] post infusion vs screening) and in association with PFS and pLOT. Results: In total, 176 CART-4 and 97 CART-1 pts received cilta-cel as study treatment. Immunophenotyping data were available from 248 peripheral blood samples (1 pLOT, n=56; 2 pLOT, n=61; ≥3 pLOT, n=131). At apheresis, CD4+ naïve T cells (%) were higher in pts with 1 or 2 pLOT, compared with those with ≥3 pLOT, while no difference was found in pts with ≥3 pLOT with further breakdown (i.e., 3–4 vs 5–6 vs ≥7 pLOT). Further, higher baseline levels of CD4+ naïve T cells were associated with longer PFS. These data suggest that the negative impact on peripheral immune fitness with the addition of LOT may plateau when pts have received ≥3 pLOT. TME gene expression data were available from 148 BMA samples (screening, n=50; D28, n=50; 6 mo, n=48) from CART-4. Analyses of gene expression signatures suggest depletion of B cells and antibodies at D28 post cilta-cel infusion, with partial recovery at 6 mo. This was corroborated in parallel by flow cytometry and immunoglobulin quantification. Further, elevated expression of genes associated with myeloid cells, including tumor-associated macrophages (TAM, likely M1), and of genes associated with cytotoxic T cells were also observed at D28. Elevated expression of genes associated with B-cell receptors, T-cell differentiation and activation, and cytokine signaling pathways were found at both D28 and 6 mo. Pts with longer PFS (>18 mo) had higher levels of M1 TAM at D28, while those with shorter PFS had higher levels of regulatory T cells and more suppressed interferon pathway genes at 6 mo, suggesting that relapse may be associated with a more suppressive immune response. In pts with fewer pLOT, more profound B-cell depletion on D28, better recovery at 6 mo, and elevated B-cell receptor signaling were inferred from gene expression data. Pts with 1 pLOT also demonstrated higher elevation of M1 TAM expression on D28 from screening as compared with pts with 3 pLOT, similar to what was observed in pts with longer PFS. Conclusions: Correlative biomarker data suggest that longer PFS is associated with better immune fitness at baseline and stronger immune responses post cilta-cel infusion, as observed in peripheral blood and within the TME of pts with RRMM in CART-1 and CART-4. The peripheral immune fitness was more pronounced in pts with 1 and 2 pLOT vs 3 pLOT and beyond, where deterioration plateaued. This suggests the impact of T-cell immune fitness on PFS may be limited beyond the third LOT. Importantly, other covariates, including factors within the immune TME and tumor burden, may play a significant role in balancing this compromised intrinsic T-cell immune fitness at apheresis, thereby contributing to PFS durability after 3 pLOT. Overall, these results support increased benefits in treating pts with MM with cilta-cel in earlier LOTs.

IntroductionThis study aims to identify barriers and enablers to the implementation of nurse-enabled subcutaneous therapy self-administration programs (NESTSPs) for patients with multiple myeloma (MM) and explore strategies to support implementation across diverse healthcare settings. Methods A qualitative, interpretive description study was conducted with patients, carers, health professionals, and policy makers. Data were collected through six focus groups and ten semi-structured interviews. Purposive sampling ensured inclusion of participants with relevant experience. Data were analysed using the Consolidated Framework for Implementation Research (CFIR), combining deductive coding with inductive theme development. Identified barriers were mapped to implementation strategies using the CFIR-Expert Recommendations for Implementing Change (ERIC) matching tool. ResultsThirty-two participants were recruited. Key barriers included limited safety, efficacy, and cost-effectiveness data; funding and regulatory constraints; workforce limitations; and resistance from organisational leadership. Enablers included strong patient-perceived benefits, such as reduced treatment burden; alignment with health system priorities; and endorsement from clinical leaders. Differences were observed between stakeholders with and without experience of NESTSPs, highlighting the role of contextual experience in shaping perceptions of feasibility and risk. ConclusionImplementation of NESTSPs for patients with MM is influenced by complex, multi-level factors spanning individual, organisational, and system contexts. While regulatory and funding barriers remain significant, strong patient-centred benefits and alignment with healthcare priorities support wider adoption. Theory-informed implementation strategies, alongside co-designed approaches tailored to local context are required to optimise scale-up and sustainability of NESTSPs. This work will be used to inform the development of a national Implementation Roadmap.

Patients with newly diagnosed multiple myeloma and considered transplant ineligible (TIE) because of age, frailty and/or comorbidities now have access to highly effective therapies that can achieve deep and/or durable remission. TIE patients are a highly heterogeneous population whose biological and chronological age can vary substantially. The treatment of these patients can be challenging in clinical practice and requires a frailty-adapted, individualised approach with an emphasis on treatment deliverability and tolerability to optimise patient outcomes. Here, we summarise recommendations for TIE patients, including pre-treatment considerations, induction and maintenance therapies, and supportive care management.

TPS7564 Background: Despite advances in MM treatment, nearly all patients (pts) will relapse, highlighting the need for new drug classes to improve outcomes in RRMM. Further, MM refractory to lenalidomide, an immunomodulatory drug (IMiD) used in frontline and maintenance therapies, poses an additional challenge as the disease is less likely to respond to subsequent treatment. G protein-coupled receptor class C group 5 member D (GPRC5D) is a promising therapeutic target for MM as the receptor is highly expressed on malignant plasma cells; it has little to no expression on non-plasma immune cells and limited expression elsewhere. Arlo-cel is a GPRC5D-directed autologous CAR T-cell therapy that has demonstrated safety and efficacy in patients with RRMM in a first-in-human ph1 study. Following a single infusion of arlo-cel at the recommended ph2 dose (RP2D) of 150 × 10 6 CAR T cells, overall response rate (ORR) was 96% (23/24) and 91% (21/23) in those with 1-3 and ≥3 prior lines of therapy (pLOT), respectively (Bal S, et al. ASH 2024. Abstracts 2069 and 922). Here we present the design of the QUINTESSENTIAL-2 study. Methods: QUINTESSENTIAL-2 (NCT06615479) is a randomized, open-label, multicenter, ph3 confirmatory study comparing the efficacy and safety of arlo-cel versus standard of care (SOC) in adults with RRMM. Pts aged ≥18 y must have received 1-3 pLOT (may include a proteasome inhibitor, IMiD, and anti-CD38 monoclonal antibody) and be refractory to lenalidomide (progression on or within 60 days of completing therapy). Additional inclusion criteria include confirmed MM diagnosis per International Myeloma Working Group criteria, measurable disease during screening, and Eastern Cooperative Oncology Group performance status 0 or 1. Eligible pts will be randomized 1:1 to one of 2 treatment arms. Arm A: single infusion of arlo-cel (RP2D of 150 × 10 6 CAR T cells), including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per Investigator within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. Arm B: SOC of DPd or Kd per Investigator, dosed per labeling. Primary endpoints are progression-free survival and minimal residual disease (MRD) negativity in complete response. Secondary endpoints include overall survival, ORR, MRD negative status, complete response rate, time to response, duration of response, pharmacokinetics, patient-reported quality of life outcomes, and safety. Pts will be followed for ≤5 years after the last patient is randomized, with a subsequent long-term follow-up study (≤15 years post infusion) for pts receiving arlo-cel. The trial is expected to enroll 440 pts across 111 sites globally, with first patient enrollment planned for Feb 2025. Clinical trial information: NCT06615479 .

Aim: Autologous anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) is now a standard-of-care for relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL), but optimal patient selection, sequencing with other novel agents and bridging strategies are areas for improvement. Tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel) have been publicly funded in Australia since January 2020 and August 2021, respectively. We evaluated the impact of baseline clinical and laboratory risk factors known at (1) apheresis and (2) pre-lymphodepletion (pre-LD), on efficacy and toxicity of CAR-T to inform clinical decision making. Methods: Adult patients with R/R LBCL eligible for CAR-T according to the Australian national criteria (ECOG <2, ≥2 prior lines or autologous stem cell transplant (autoSCT), adequate organ function) were included if they underwent apheresis with intent to receive CAR-T at 6 Australian centres between January 1, 2020 and December 31, 2024. For infused patients, progression-free survival (PFS) and overall survival (OS) were calculated from date of infusion. Univariable and multivariable Cox proportional hazards (CoxPH) models using routinely-available risk factors were applied at apheresis and pre-LD, and predictive scoring systems were established. Results: 632 patients were included. The median age was 66 years (16 to 85), histologies were high-grade B-cell lymphoma (HGBL) 11%, diffuse large B-cell lymphoma (DLBCL) 63%, transformed lymphoma 16%, Richters transformation 4%, primary mediastinal large B-cell lymphoma (PMBCL) 2%, T-cell/histiocyte rich large B-cell lymphoma (THRLBCL) 2%. Bridging therapy was used in 87% (46% systemic, 24% radiotherapy, 17% combined). 210 tisa-cel-intended patients underwent apheresis; 190 (90%) were infused. The best overall and complete response rates (ORR and CRR) were 73% and 59%, respectively. The 12-month PFS was 34% (intention-to-treat (ITT)), and 38% (infused). Grade (G) ≥3 CRS occurred in 9%, and G≥3 ICANS in 7%. 422 axi-cel-intended patients underwent apheresis; 395 (94%) proceeded to infusion. The best ORR and CRR were 85% and 72%, respectively. The 12-month PFS was 47% (ITT), and 50% (infused). G≥3 CRS occurred in 4%, and G≥3 ICANS occurred in 22%. CoxPH factors included: age (>75 vs ≤75), sex, ECOG (0 vs ≥1), histology (HGBL vs DLBCL vs transformed lymphoma), number of prior lines of therapy (2 vs 3 vs ≥4), prior autoSCT, history of primary refractory disease, relapsed/refractory to most recent systemic therapy, LDH (high vs normal), bridging response (PD/SD vs PR/CR vs no bridging, at pre-LD only). At time of apheresis, a two-factor model including relapsed/refractory status and LDH was selected. For tisa-cel patients the 12-month PFS (ITT) stratified by number of risk factors was, 0: 58% (44–76%), 1: 33% (24–45%), and 2: 24% (16–37%). Rates of failure to infuse were, 0: 5%, 1: 8%, and 2: 18%. For axi-cel 12-month PFS (ITT) was: 0: 63% (50–78%), 1: 53% (45–63%), and 2: 37% (30–45%). Rates of failure to infused were, 0: 2%, 1: 6%, and 2: 8%. At pre-LD, a three-factor model including ECOG, bridging response and LDH, was selected. For tisa-cel patients the 12-month PFS (infused) stratified by number of risk factors was, 0: 72% (58–89%), 1: 49% (38–63%), 2: 28% (17–46%), and 3: 3% (0–23%). For axi-cel 12-month PFS (infused) was, 0: 66% (54–80%), 1: 65% (55–76%), 2: 52% (43–63%), and 3: 23% (15–35%). Amongst tisa-cel patients with all 3 risk factors, the rate of G≥3 CRS was 22% and G≥3 ICANS was 12%, compared with 5% and 7%, respectively, with ≤2 risk factors. Amongst axi-cel patients with all 3 risk factors, the rate of G≥3 CRS was 9% and G≥3 ICANS was 31%, compared with 2% and 19%, respectively, with ≤2 risk factors. Conclusions: Real-world Australian outcomes of CAR-T for R/R LBCL in third-line and beyond are favourable. A two-factor model at pre-apheresis (relapsed/refractory status and LDH) and a three-factor model at pre-LD (ECOG, bridging response and LDH) stratifies for both PFS and high-grade toxicity risk. Response to bridging was associated with improved outcomes with either product. In the absence of identified risk factors outcomes were excellent with either product, with axi-cel more effective relative to tisa-cel as risk factors increased. These findings offer a simple and clinically useful framework for consideration of patient selection, product choice and bridging strategy in the era of alternative highly-effective therapies.

Aim: To compare baseline characteristics, treatments and outcomes in newly diagnosed multiple myeloma (NDMM) patients based on the number of high-risk cytogenetic abnormalities (HRCA) present. Method: We analyzed Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) patients from 2012 to 2025 with NDMM and fluorescent in situ hybridization (FISH) cytogenetic data available. Patients were grouped based on the number of HRCA present (HRA0, HRA1 and HRA2+), including t[4;14], t[14;16], del[17p] and gain[1q]. Results: Of 5927 NDMM patients identified on the MRDR, 3397 (57%) patients had available myeloma FISH results which were categorised into HRA0 (2406, 70.8%), HRA1 (808, 23.8%) and HRA2+ (183, 5.4%). Patients with multiple HRCA were more likely to be female, have higher lactate dehydrogenase (LDH) and β2-microglobulin levels at diagnosis. Patients with 2 or more HRCA were more likely to present with anaemia (haemoglobin <100 g/L), thrombocytopenia and greater bone marrow plasma cell burden at diagnosis (p<0.001). Paraprotein subclass also differed across the groups; patients with increasing HRCA were more likely to produce IgA paraprotein (17.1% HRA0 vs 33.3% HRA2+) and less likely to produce IgG paraprotein (59.7% HRA0 vs 44.8% HRA2+) [p<0.01]. There was no statistically significant difference between the groups in the incidence of bone disease, white cell count or renal function (median serum creatinine) at diagnosis. The cumulative presence of HRCA at diagnosis was associated with shorter progression-free survival (PFS) [median 35.6 months for HRA0, 25.7 for HRA1 and 20.2 for HRA2+ (p<0.001)]. Similarly, increasing numbers of HRCA correlated with poorer overall survival (OS) [median OS was 86.1, 56.6 and 37.5 months respectively (p<0.001)]. Overall survival was significantly worse for those with del(17p) as the only HRCA compared to other single HRCA. However, the addition of other HRCA with del(17p) did not affect OS compared to del(17p) alone. Patients with gain(1q) were more likely to have concurrent del(17p) than those without gain(1q) (12.7% vs 6.3%, p<0.001). Most patients in each HRCA group received bortezomib-based first-line therapy in combination with cyclophosphamide or lenalidomide. Despite similar overall response rate across the HRCA groups (84% HRA0, 87% HRA1, 88% HRA2+), the duration of treatment response was significantly shorter with increasing HRCA burden [median duration: 30.9 months (HRA0), 19.1 months (HRA1), 16.8 months (HRA2+)(p<0.001)] Conclusion: This real-world data confirms that increasing HRCA burden in NDMM is associated with distinct disease characteristics and poorer clinical outcomes, including shorter PFS and OS despite similar overall response rates between the three groups. However, the addition of other HRCA with del(17p) did not affect OS compared to del(17p) alone which remained to greatest risk single HRCA.

Background In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes. Methods In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 106 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing. Findings Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and –1·5 (95% CI –5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI –1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care. Interpretation Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease. Funding Janssen Research & Development, Legend Biotech USA.

Background Multiple myeloma (MM) is associated with the greatest symptom burden of all hematological cancers and, despite substantial improvements in treatment options with high response and survival rates, is still considered incurable, with patients undergoing multiple lines of therapy over many years. Subcutaneous (SC) injections are a common mode of delivery for current and future MM therapy, with evidence suggesting that programs that give patients or carers responsibility for administration can bring benefits to the patient and health care system by reducing the number of required visits to hospital. Objective This study will explore and describe barriers to and enablers of implementing nurse-enabled SC therapy self-administration programs for patients with MM to develop a road map for national scalability. Methods This qualitative descriptive study is informed by the Consolidated Framework for Implementation Research. Participants included key stakeholders from across Australia, including patients, carers, health professionals, and policymakers with experience of implementation, facilitation, and participation in nurse-enabled SC therapy self-administration programs. Data were collected via virtual focus groups or semistructured interviews and analyzed using the framework method to identify barriers and enablers. The Expert Recommendations for Implementing Change matching tool will be used to develop strategies to target barriers and enhance enablers, informing the development of a national road map. Results This study was funded in March 2024 and approved by Peter MacCallum Cancer Centre Human Research Ethics Committee in May 2024. Data collection was conducted between June 2024 and November 2024. A total of 32 participants were recruited. Data analysis is underway, with results expected to be published in February 2026. Conclusions To our knowledge, this study will be the first of its kind to identify and compare barriers to and enablers of implementing nurse-enabled SC self-administration programs for patients with MM. Applying the Consolidated Framework for Implementation Research to guide study processes provides an evidence-informed approach to understanding how discrete and intersecting factors influence program implementation and sustainability, informing the development of a comprehensive implementation road map. As the availability of SC therapies grows for other cancers and chronic diseases, this model of care could serve as a blueprint for broader applications, impacting patient quality of life and optimization of health care use.