BACKGROUND:A growing number of patients with multiple myeloma are anti-CD38 antibody-exposed and lenalidomide-exposed at first relapse, subsequently limiting their treatment options. Mezigdomide, a potent cereblon E3 ligase modulator, induces maximal, rapid Ikaros and Aiolos degradation, resulting in enhanced myeloma cell cytotoxicity and immune stimulation versus immunomodulatory drugs. The SUCCESSOR-2 trial evaluates the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone versus carfilzomib plus dexamethasone. METHODS:This phase 3, open-label, randomised controlled trial was conducted at 160 hospital-based sites in 26 countries using a two-stage, inferentially seamless design. Eligible adult patients had measurable multiple myeloma, had received at least one previous regimen (including anti-CD38 antibodies and lenalidomide) on which they had achieved minimal response or better, and documented disease progression during or after their most recent treatment. Interactive response technology was used to randomly assign patients, stratified by age (≤70 years or >70 years), number of previous lines of therapy (≤2 or >2), and International Staging System stage (I, II, or III). Patients received oral mezigdomide (days 1-21 of each 28-day cycle) plus intravenous carfilzomib (56 mg/m2 weekly) and oral or intravenous dexamethasone (40 mg weekly) or carfilzomib (56 mg/m2 twice weekly or 70 mg/m2 weekly) and dexamethasone (20 mg twice weekly or 40 mg weekly). In stage 1, mezigdomide dosing across three levels was optimised. In stage 2, patients were randomly assigned to the selected mezigdomide dose (1·0 mg) plus carfilzomib and dexamethasone or carfilzomib-dexamethasone alone. The primary endpoint was progression-free survival (PFS) evaluated in patients who received 1·0 mg mezigdomide plus carfilzomib and dexamethasone or carfilzomib-dexamethasone alone across both study stages. No imputation was planned for missing efficacy endpoint values or missing safety evaluations. The trial is registered with ClinicalTrials.gov (NCT05552976) and EUClinicalTrials.eu (EUCT number 2022-500861-29-00). The trial is active but not recruiting. FINDINGS:Between Feb 3, 2023, and Nov 28, 2025, 762 patients were assessed for eligibility, of which 606 patients were enrolled and 479 were included in the analyses (288 patients in the mezigdomide-carfilzomib-dexamethasone group and 191 patients in the carfilzomib-dexamethasone group). 252 (53%) patients were male, 411 (86%) were anti-CD38 antibody-refractory, and 363 (76%) were lenalidomide-refractory, with a median of two previous lines of therapy (IQR 2-4). At 10·6 months median follow-up, mezigdomide-carfilzomib-dexamethasone significantly improved PFS compared with carfilzomib-dexamethasone (median 18·0 months vs 8·3 months; hazard ratio 0·48 [95% CI 0·36-0·63]; p<0·0001). Grade 3 or 4 adverse events were observed in 241 (84%) patients receiving mezigdomide-carfilzomib-dexamethasone versus 105 (56%) patients receiving carfilzomib-dexamethasone, including neutropenia (176 [61%] vs 17 [9%]) and infections (98 [34%] vs 29 [16%]). Eight (3%; 95% CI 1-5) and one (1%; 95% CI 0-3) treatment-related grade 5 adverse events were reported with mezigdomide-carfilzomib-dexamethasone and with carfilzomib-dexamethasone, respectively (rate difference 2%; 95% CI -1 to 5). Deaths occurred in 62 (22%) patients in the mezigdomide-carfilzomib-dexamethasone group and 51 (27%) patients in the carfilzomib-dexamethasone group, mainly due to disease progression. INTERPRETATION:Mezigdomide-carfilzomib-dexamethasone provided a significant PFS benefit compared with carfilzomib-dexamethasone alone, with higher rates of grade 3 or 4 adverse events, including infections, which were mostly manageable with standard clinical practice and supportive care. These findings support mezigdomide-carfilzomib-dexamethasone as a clinically meaningful treatment option as early as first relapse in predominantly triple-class-exposed, anti-CD38 antibody-refractory and lenalidomide-refractory patients, a growing population with substantial unmet need. FUNDING:Bristol Myers Squibb.

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.

TPS7577 Background: Despite advances in multiple myeloma (MM) treatment, most patients (pts) will relapse, highlighting the need for new drug classes in RRMM. Further, with the extensive use of lenalidomide (LEN), an immunomodulatory drug (IMiD), in frontline and maintenance therapies, LEN-refractoriness has become increasingly common and 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 cell immune populations and limited expression on other tissues. Arlocabtagene autoleucel (arlo-cel) is a GPRC5D-directed autologous CAR T cell therapy that has demonstrated safety and efficacy in pts with RRMM in a first-in-human phase 1 study. ORR was 94% and 91% in pts with 1-3 and ≥3 prior LOT (pLOT), respectively, after a single arlo-cel infusion (150×10 6 CAR T-cells); ORR was 92% in pts with ≥3 pLOT following a 75×10 6 CAR T cell infusion. These phase 1 study outcomes support further clinical development of arlo-cel. Methods: QUINTESSENTIAL-2 (NCT06615479) is a randomized, open-label, multicenter, phase 3 confirmatory study comparing the efficacy and safety of arlo-cel vs SOC in adults with RRMM and prior LEN. Key inclusion criteria were age ≥18 years, confirmed diagnosis of MM per IMWG criteria, 1-3 pLOT (may include a proteasome inhibitor, IMiD, anti-CD38 antibody, and BCMA-targeted therapy), be exposed to LEN (≥2 consecutive cycles, unless PD was the best response to LEN-containing treatment or if there was LEN intolerance or unacceptable toxicity), have measurable disease, and ECOG PS of 0 or 1. Pts who received prior GPRC5D-targeted therapy are excluded. Eligible pts will be randomized 1:1 across 2 arms. Arm A includes leukapheresis within 3-4 days of randomization, mandatory bridging therapy ≤6 days of randomization with DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per investigator choice 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 PD. Primary endpoints are PFS and minimal residual disease (MRD) negativity in CR. Key secondary endpoints include OS and ORR. Other endpoints include safety, MRD-negative status, CR rate, time to response, duration of response, pharmacokinetics, and pt-reported outcomes. Pts will be followed for ≤5 years after the last pt is randomized, and with a long-term follow-up study (≤15 years post-infusion) for pts receiving arlo-cel. Anticipated enrollment is 440 pts at ~125 sites globally. The first pt was enrolled in March 2025. © American Society of Hematology (2025). Reused with permission. Clinical trial information: NCT06615479 .

7516 Background: With the growing use of anti-CD38 therapies in early multiple myeloma (MM) management, there is a need for data in patients previously exposed to anti-CD38 therapy to guide decision making. In the Phase 3 IRAKLIA trial (NCT05405166), patients with relapsed/refractory MM (RRMM) received the anti-CD38 monoclonal antibody isatuximab (Isa) subcutaneously (SC) delivered via an innovative on-body injector (OBI) or intravenously (IV), with pomalidomide and dexamethasone (Pd). In this post hoc analysis, we examined outcomes in IRAKLIA patients with vs without prior anti-CD38 exposure. Methods: RRMM patients ≥18 years with ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor were randomized to receive Isa SC (n=263) or IV (n=268) weekly in Cycle 1, then every 2 weeks, with Pd. Patients with prior anti-CD38 exposure <9 months (mos) before randomization or intolerance to anti-CD38 were excluded. Refractory patients were defined as those who failed to achieve minimal response on treatment or had progression within 60 days after last dose. Patients receiving Isa SC or IV were pooled. Results: Overall, 67 patients (12.6%) had prior anti-CD38 exposure with a median washout period of 20.2 mos, of which 26 (38.8%) were anti-CD38 refractory. Baseline characteristics were largely consistent between patients with or without prior anti-CD38 exposure; the median follow-up for the overall population was 12 mos. Patients with prior anti-CD38 exposure had an overall response rate (ORR) of 52.2%, 12-mo progression-free survival (PFS) rate of 40.6%, and median PFS of 8.5 mos. In patients without prior exposure, an ORR of 73.5%, 12-mo PFS of 68.8%, and non-estimable (NE) median PFS were reported. Anti-CD38 non-refractory vs refractory patients had an ORR of 48.8% vs 57.7%, 12-mo PFS of 38.9% vs 42.2%, and median PFS of 9.0 vs 7.5 mos. Patients with a longer washout period (>median of 20.2 mos) had an ORR of 63.6%, 12-mo PFS of 61.8% and NE median PFS, whereas patients whose prior anti-CD38 therapy ended more recently (≤median of 20.2 mos) had an ORR of 41.2%, 12-mo PFS of 19.2%, and median PFS of 6.7 mos. The safety profile of Isa + Pd was similar in patients with vs without prior anti-CD38 exposure. Conclusions: Isa + Pd demonstrated clinical benefit across anti-CD38–naïve, anti-CD38–exposed, and anti-CD38–refractory patients. A washout period >median of 20.2 mos resulted in outcomes comparable to those in anti-CD38–naïve patients, and outcomes were consistent between anti-CD38–exposed and anti-CD38–refractory patients after a >9-mo washout period. Efficacy of Isa + Pd in patients with prior anti-CD38 exposure from the IRAKLIA trial presents an opportunity to address an unmet need in a difficult-to-treat patient population. Clinical trial information: NCT05405166 .

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.

The survival of newly diagnosed patients with multiple myeloma has improved significantly over the past 20 years with significant therapeutic advances. Despite this, high-dose chemotherapy followed by autologous stem cell transplantation remains the standard of care in newly diagnosed patients who are considered transplant eligible. Here, we summarise the recommendations of the Medical and Scientific Advisory Group of Myeloma Australia for patients considered suitable for high-dose chemotherapy and autologous stem cell transplantation as part of the initial therapy.

Abstract Urothelial carcinoma arises from a “field” of precancerous but histologically normal urothelium. The KMT2C/D-KDM6A complexes known to bind and activate enhancers are frequently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using a genetically engineered mouse model, we demonstrate that knockout of Kmt2c and/or Kmt2d induced a histologically normal, pre-tumorigenic state characterized by impaired differentiation from basal state and by augmented responses to growth and inflammatory stimuli. This sensitized the urothelium to transformation by known oncogenic drivers in urothelial carcinoma. Mechanistically, Kmt2d localized to both active enhancers and a small group of CpG-poor promoters and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which together led to downregulation of the urothelial differentiation program. We further observed that Menin distributed extensively to Kmt2d localized enhancers and Kmt2c/d knockout led to redistribution of Menin to CpG-high and particularly bivalent promoters, resulting in transcriptional de-repression of bivalent genes. Blockade of Kmt2a/b-Menin interaction partially rescued the transcriptional changes that induced by Kmt2c/d deletion. Therapeutically, Kmt2c/d knockout maintained a basal state that upregulated EGFR signaling and conferred vulnerability to EGFR inhibitors. Together, our data posits that functional loss of Kmt2c/d licenses a molecular “field effect” priming histologically normal urothelium for oncogenic transformation and leading to therapeutic vulnerabilities to EGFR signaling pathway inhibition. Citation Format: Naitao Wang, Mohini Pachai, Dan Li, Cindy Lee, Sarah Warda, Makhzuna Khudoynazarova, Woo Hyun Cho, Guojia Xie, Fengshen Kuo, Sagar Shah, Li Yao, Cheng Qian, Elissa Wong, Juan Yan, Fanny Tomas, Wenhuo Hu, Sizhi Gao, Alison Smith, Ming Han, Dong Gao, Kai Ge, Haiyuan Yu, Sarat Chandarlapaty, Gopakumar Iyer, Jonathan Rosenberg, David Solit, Hikmat AI-Ahmadie, Ping Chi, Yu Chen. Kmt2c/d loss primes urothelium for tumorigenesis and redistributes Menin to bivalent promoters [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A012.

Background:Patients (pts) with multiple myeloma (MM) often receive immunomodulatory drugs (IMiDs; eg, lenalidomide), proteasome inhibitors (eg, bortezomib), and anti-CD38 monoclonal antibodies (mAbs) as part of their initial treatment. However, most pts relapse following initial treatment, with increasing attrition rates observed at each subsequent line of therapy (LOT), creating an unmet need for treatment options for pts with relapsed/refractory MM (RRMM) who have prior exposure to these agents. Current regimens for pts who have prior exposure to lenalidomide and anti-CD38 mAbs include elotuzumab, pomalidomide, and dexamethasone (EPd; approved in Europe and the US) and pomalidomide, bortezomib, and dexamethasone (PVd; approved in Europe and Australia), but disease control, as well as depth and durability of response, could be improved. Talquetamab (tal) and teclistamab (tec), targeting CD3 and either G protein-coupled receptor family C group 5 member D (GPRC5D, tal) or B-cell maturation antigen (tec), are the first T-cell redirecting bispecific antibodies (BsAbs) approved as monotherapies in Europe and the US for the treatment of pts with triple-class exposed (TCE) RRMM. Use of these novel immunotherapies in earlier LOTs, either with a dual-antigen targeting approach or by enhancing the activity of the BsAb with an IMiD (pomalidomide), may provide deeper, more durable responses and improve pt quality of life. Preliminary data using these combination treatments have shown promising results: in the phase 1b MonumenTAL-2 study (NCT05050097), tal+pomalidomide (tal-P) demonstrated overall response rates (ORRs) of >84% in pts with RRMM with ≥2 prior LOTs and in the phase 1b/2 RedirecTT-1 study (NCT04586426), tal+tec (tal-tec) showed ORRs of >77% in pts with TCE RRMM. MonumenTAL-6 (NCT06208150) is a randomized, open-label, multicenter, phase 3 study comparing the efficacy of tal-P vs investigator's choice of EPd or PVd and tal-tec vs investigator's choice of EPd or PVd in pts with RRMM with 1-4 prior LOTs, including lenalidomide and an anti-CD38 mAb. Study Design and Methods: Eligibility includes pts aged ≥18 years with documented MM per International Myeloma Working Group (IMWG) criteria, with measurable disease at screening, an Eastern Cooperative Oncology Group performance status of 0-2, who have received 1-4 prior LOTs (including lenalidomide and an anti-CD38 mAb in any prior LOT), and have progressive disease on or after their last therapy. Pts with prior exposure to pomalidomide, tec, or GPRC5D-directed therapies are excluded. Approximately 795 pts are randomized 1:1:1 to receive tal-P, tal-tec, or investigator's choice of EPd or PVd. Tal is administered subcutaneously at 0.8 mg/kg every other week (Q2W), and tec is administered subcutaneously at 3.0 mg/kg every 4 weeks (Q4W) following step-up doses of each. Pts are permitted to switch from Q2W to Q4W tal dosing following a confirmed very good partial response or better (≥VGPR) at cycle 5. Pomalidomide, EPd, and PVd are administered per approved dosing schedules. Randomization is stratified by number of prior LOTs (1 vs ≥2), International Staging System stage at screening (I vs II/III), and investigator's choice of treatment (EPd vs PVd). Pts receive study treatment until disease progression, start of subsequent anti-MM treatment, death, intolerable toxicity, withdrawal of consent, or end of study, whichever occurs first. A finite dosing approach is employed for tal and tec. The primary endpoint is progression-free survival (PFS). Secondary endpoints include ORR assessed per IMWG 2016 criteria, ≥VGPR rate, complete response (CR) or better rate, rate of minimal residual disease-negative CR, overall survival, PFS on next LOT, time-to-next treatment, and pt-reported outcomes. This study is actively recruiting, with more than 160 locations in 26 countries. Results will provide insights into the efficacy of the combination of BsAbs in therapeutic strategies that exploit their different mechanisms of action to overcome treatment resistance and improve outcomes of pts with TCE RRMM in earlier LOTs.

Abstract Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. Conclusions: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.

Background Since 2010, Taiwan has conducted a population-based breast cancer screening programme that includes mobile units to improve the screening rate. This study aimed to compare the results of mobile breast cancer screening units with those of hospital-based units and estimate the preclinical detectable phase (PCDP) transition time for Taiwanese women with breast cancer. Methods This retrospective cohort study included women aged 45 to 69 years who participated in the programme from 2010 to 2018, with at least two years of follow-up, allowing time to detect breast cancer and determine mortality status. The five-state Markov exponential regression model was used to find (1) the underlying incidence of breast cancer for each location type and (2) the sensitivity that each mammography type offers for detecting PCDP early- and late-stage asymptomatic breast cancer. These parameters shed light on the natural history of breast cancer. Results Between 2010 and 2018, 2 387 756 women were screened via 6 313 607 mammograms, 55% of which were performed in hospital-based units. The annual pre-clinical incidence rate per person was 0.0035 (95% CI = 0.0035-0.0036) in hospital units, greater than that in mobile units (0.0022, 95% CI = 0.0022-0.0022). The progression rate from early to late stage within the PCDP was 0.2950 (95% CI = 0.2877-0.3025). The progression rates to the clinical phase from PCDP with early- and late-stage breast cancer were 0.1762 (95% CI = 0.1713-0.1811) and 0.4157 (95% CI = 0.4056-0.4258), leading to calculated mean sojourn times of 3.50 (95% CI = 3.45-3.56) years and 2.36 (95% CI = 2.30-2.42) years, respectively. Using computed radiography to collect the mammograms during PCDP with early-stage breast cancer resulted in a sensitivity of 0.503 (95% CI = 0.484-0.521), whereas using digital radiography resulted in a sensitivity of 0.669 (95% CI = 0.653-0.684). When used during PCDP with late-stage breast cancer, these sensitivities were 0.629 (95% CI = 0.609-0.648) and 0.797 (95% CI = 0.782-0.811), respectively. Conclusions The incidence of breast cancer was greater among women visiting in-hospital screening than mobile screening, and the mammogram type was the primary factor affecting sensitivity for detecting asymptomatic breast cancer.

Background The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan’s Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50–69 years since 2004 and for those aged 45–69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004–2009) and latter (2010–2020) periods. Methods A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. Results Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004–2009) and latter (2010–2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83–9.97%) in the early period and decreased to 8.15% (95%CI, 8.13–8.17%) in the latter period. Conclusions The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Early detection decreases breast cancer death. The ACR recommends annual screening beginning at age 40 for women of average risk and earlier and/or more intensive screening for women at higher-than-average risk. For most women at higher-than-average risk, the supplemental screening method of choice is breast MRI. Women with genetics-based increased risk, those with a calculated lifetime risk of 20% or more, and those exposed to chest radiation at young ages are recommended to undergo MRI surveillance starting at ages 25 to 30 and annual mammography (with a variable starting age between 25 and 40, depending on the type of risk). Mutation carriers can delay mammographic screening until age 40 if annual screening breast MRI is performed as recommended. Women diagnosed with breast cancer before age 50 or with personal histories of breast cancer and dense breasts should undergo annual supplemental breast MRI. Others with personal histories, and those with atypia at biopsy, should strongly consider MRI screening, especially if other risk factors are present. For women with dense breasts who desire supplemental screening, breast MRI is recommended. For those who qualify for but cannot undergo breast MRI, contrast-enhanced mammography or ultrasound could be considered. All women should undergo risk assessment by age 25, especially Black women and women of Ashkenazi Jewish heritage, so that those at higher-than-average risk can be identified and appropriate screening initiated.

raw uncropped labeled western blots

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.