Lower Rate Of Disease Progression Research Articles

Multimodal artificial intelligence models from baseline histopathology to predict prognosis in HR+ HER2- early breast cancer: Subgroup analysis.

101 Background: Prognostic assessment in HR+ HER2- early breast cancer (EBC) remains challenging given relatively low rates of disease progression. Modern artificial intelligence (AI)-based techniques have already provided substantial medical progress, particularly in prostate cancer. We have leveraged ArteraAI’s multimodal artificial intelligence (MMAI) platform to develop a research-level prognostic model in HR+ HER2- EBC, based on the WSG PlanB and ADAPT trials. Here, we quantify the value added by MMAI within clinically relevant subgroups. Methods: Histopathology image data was generated from pre-treatment breast biopsy and surgical hematoxylin and eosin (H&E) slides from the WSG PlanB and ADAPT trials. Patients with available images and complete data (n=5259) were allocated (stratified by trial, randomization arm and distant recurrence (DR)) to development (60%) and validation (40%) cohorts. An MMAI-based model using image data combined with clinical prognostic variables (age, T and N stage, tumor size) was developed to predict risk of DR. Univariable and multivariable Fine-Gray models were used to assess performance in the validation cohorts; subdistribution hazard ratios (sHR) refer to validation cohorts and are reported per standard deviation increase of the model scores (image-alone or combined). Pre-specified prognostic subgroups for analysis were defined by nodal status, menopausal status, and central tumor grade. All statistical tests were 2-sided at .05 significance. Results: The trained MMAI score was significantly associated with risk of DR in the validation cohort (sHR [95% CI] = 2.3 [2.0-2.8]) as a whole and in all considered subgroups. The score remained significant (sHR [95%CI] = 2.2 [1.7-2.8]) after adjusting for clinical prognostic factors. Moreover, the MMAI image component alone had significant prognostic value (sHR [95%CI] = 1.6 [1.3 - 1.9]) in the validation cohort. Remarkably, the MMAI image component alone had significant prognostic value separately within the G2 and G3 sub-groups, with sHR of about 1.5 per standard deviation increase, and also in most of the other predefined clinical subgroups. Conclusions: Preliminary results from the current MMAI breast model provide evidence that ArteraAI MMAI technology can be leveraged for outcome prediction in HR+ HER2- EBC using H&E-stained images to further personalize breast cancer management. The ability of image-only AI models to provide significant prognostic value within grade subgroups suggests that self-supervised AI has identified some novel image features with prognostic value beyond grade. To put the results into the clinical context, comprehensive validation analyses will be presented at the meeting.

Abstract PO4-01-10: Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer

Abstract Background: Prognostic assessment in HR+ HER2- early breast cancer (EBC) remains challenging given relatively low rates of disease progression. Nuanced risk stratification is needed for decisions regarding systemic therapy. Modern artificial intelligence (AI)-based techniques have already provided substantial medical progress, particularly in prostate cancer. Here, we leverage multi-modal artificial intelligence (MMAI) trained using digital histopathology and clinical data to evaluate whether the MMAI technology can be expanded to other disease indications by applying the technology to the WSG PlanB and ADAPT trials in HR+ HER2- EBC. Methods: Pre-treatment breast biopsy and surgical hematoxylin and eosin (H&E) slides were digitized from the WSG PlanB and ADAPT trials for HR+ HER2- EBC patients receiving endocrine therapy +/- chemotherapy. Median follow-up in both trials exceeded 5 years. A multi-modal artificial intelligence architecture was developed and validated on predicting risk of distant recurrence (DR). Time-to-event endpoints were summarized using cumulative incidence curves. Univariable and multivariable Fine-Gray models were used to assess performance; hazard ratios were reported per standard deviation increase of the model score. Results: A total of 5539 patients from the two trials with H&E images and available follow-up data were used for development and validation of a multi-modal artificial intelligence architecture. The MMAI score derived using the training set was significantly associated with risk of DR in a validation cohort. To put the results into the clinical context in HR+ HER2- EBC, comprehensive validation analyses are currently ongoing and will be presented at the meeting. Conclusions: We have successfully developed a multiple-instances, learning-based deep neural network for outcome prediction using H&E-stained images. This study provides important evidence that MMAI technology can further personalize breast cancer management by adding standardizable information. Citation Format: Daniel Kates-Harbeck, Hans-Heinrich Kreipe, Oleg Gluz, Matthias Christgen, Sherko Kuemmel, Monika Graeser, Ulrike Nitz, Sven Mahner, Doris Mayr, Rachel Wuerstlein, Akinori Mitani, Jingbin Zhang, Hans Pinckaers, Yi Ren, Peter Wood, Jacqueline Griffin, Felix Feng, Andre Esteva, Jess Keim-Malpass, Ronald Kates, Nadia Harbeck. Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-10.

Abstract PO5-17-10: PERFORMANCE AND OUTCOMES OF THE 70-GENES SIGNATURE (MAMMAPRINT™) IN A POPULATION WITH MIDDLE INCOME – REAL WORLD STUDY (AGEMA-BRA)

Abstract INTRODUCTION – Breast cancer remains the most frequent tumor in the female population and the fourth in mortality in the world population (GLOBOCAN 2020). With the aim of reducing mortality and at the same time de-escalating treatment, avoiding overtreatment, individualized therapy is increasingly being applied. The genomic signature of 70-genes, when stratifying patients into high and low risk of relapse, makes it possible to withdraw part of the cases of high clinical risk from chemotherapy treatment. However, the MINDACT study, which validated this signature, was carried out only in the European population, with no data on performance and outcomes in other populations with greater miscegenation. OBJECTIVE – To study the performance and outcomes of the 70-gene genomic signature (MammaPrint™) in a Brazilian population with a high ethnic miscegenation. METHODOLOGY – A retrospective cohort study was conducted in 953 women with breast cancer at high clinical risk, who underwent genomic analysis with the 70-gene platform (MammaPrint™), from January 2016 to December 2020. For the statistical evaluation, a descriptive analysis of the data with absolute and relative frequencies of the variables was performed. To verify the association between qualitative variables, the chi-square test was used. All analyzes were performed in the R 4.1.0 environment (R Core Team, 2021). Study approved by the Research Ethics Committee of the State University of Ponta Grossa (PR) - (CAAE: 12194219.4.0000.0105). RESULTS – The analysis of 955 cases from the AGEMABRA cohort (all at high clinical risk) showed 546 cases (57.2%) with low genomic risk and 409 cases (42.8%) with high genomic risk to MammaPrint™ (MP); when compared with data from the MINDACT study (46.2% low risk and 53.8% high risk) a significant difference was observed in the distribution for high and low risk in the two populations (p.< 0.001). After excluding patients with missing data, 409 cases of low- and high-risk MP were studied. The variables regarding age group, tumor diameter, number of affected lymph nodes, hormone receptors and HER2 overexpression showed no significant difference; within this same analysis, the tumor grade showed a higher incidence of grade 1 in the population with low genomic risk (6.6%) compared to high risk (2.9%) and grade 3 in high risk (13%) compared to low risk (5%) with p.< 0.001 (table 1). With an average follow-up of 40 months, the DMFS (disease metastatic free survival) found was 97.2%, being 97.8% for low risk and 96.2% for high risk (p.0.54). All patients with high-risk MP who progressed had used adjuvant chemotherapy, and all patients with low-risk MP who relapsed received only endocrine therapy. When compared to the MINDACT population, the AGEMA-BRA has more elderly patients, and smaller tumors with a lower histological grade (p.=< 0.001). CONCLUSION – The analysis of the Brazilian population submitted to the 70-gene genomic signature showed a greater proportional number of tumors with low genomic risk than in the test approval study, favoring its application with the aim of de-escalating systemic treatment in this population. Despite the low rate of disease progression in the AGEMA-BRA study, probably determined by the population with the best prognosis disease and the short follow-up, recurrence was similar in the high and low genomic risk groups, demonstrating the adequate selection of systemic therapy following the results of the MP. An increase in the sample size and longer follow-up are necessary to confirm the results found. Table 1. Characteristics of patients and tumor according to risk (AGEMA-BRA) Citation Format: Fabio Mansani, Ruffo Freitas-Junior. PERFORMANCE AND OUTCOMES OF THE 70-GENES SIGNATURE (MAMMAPRINT™) IN A POPULATION WITH MIDDLE INCOME – REAL WORLD STUDY (AGEMA-BRA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-10.

Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp.

1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.

Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review.

Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression.

Impact of Genetic Mutations on Survival Following Receipt of Commercial CART19 for Patients Diagnosed with Aggressive B Cell Lymphoma

Introduction Anti-CD19 chimeric antigen receptor-modified T cell therapies (CART19) have revolutionized treatment of patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) and high grade B cell lymphoma (HGBL). However, progression of disease following receipt of CART19 is common with only approximately one-third of pts achieving long-term remission in the standard-of-care setting (Transplant Cell Ther. 2022 Sep;28(9):581.e1-581.e8, Blood (2022) 140 (Supplement 1): 1584-1587). While loss of CD19 antigen expression antigen is one mechanism of CART19 failure, other tumor-intrinsic factors which may result in CART19 failure remain poorly defined. Clinical laboratory mutation analysis (CLMA) performed on tumor specimens can identify recurring genetic mutations which may predict for clinical outcomes; however, the predictive value of CMLA has not been well-established for DLBCL/HGBL pts treated with CART19. Here, we analyze the impact of genetic mutations as detected by CLMA, along with other clinicopathologic characteristics, on survival outcomes of DLBCL/HGBL pts following receipt of CART19. Methods We collected data from 46 pts with DLBCL or HGBL treated at the University of Pennsylvania between 2018 and 2021. Patient tumors were sequenced with one of three sequencing panels comprised of 41-116 genes prior to receiving commercial CART19. Cox proportional hazards regression was used to assess the impact of clinicopathologic characteristics on disease progression and death, with characteristics demonstrating p &amp;lt;0.10 on univariate analysis included in multivariate analysis. Estimated progression free survival (PFS) and overall survival (OS) from the time of CART19 infusion were calculated using Kaplan-Meier estimates. Results Baseline clinicopathologic characteristics are listed in Table 1. A total of 30 of 46 pts had at least one tumor mutation detected prior to receiving CART19, with 22 genes mutated in at least two pts (Figure 1). The most frequent mutations were TP53 (15 of 46, 32.7%), BCL2 (3 of 12, 25%), MYC (4 of 20, 20%), SOCS1 (5 of 38, 13.2%), CD79B (5 of 38, 13.2%), CREBBP (5 of 38, 13.2%), EZH2 (5 of 46, 10.9%), STAT3 (4 of 38, 10.5%), TNFRSF14 (4 of 38, 10.5%) and DNMT3A (2 of 20, 10%). The median length of follow-up from the time of CART19 infusion was 29.6 months. For all pts, the rates of 2 year (y) PFS and OS were 21% (95% confidence interval [CI] 10-34%) and 56% (95% CI 40-69%), respectively. Univariate analysis of mutations present in ≥10% of cases revealed that TNFRSF14 mutations predicted for lower risk of disease progression at 2y (HR 0.16, 95% CI 0.02-1.186, p = 0.07). No other mutation was associated with either disease progression or death at 2y. Univariate analysis of baseline clinicopathologic characteristics also identified International Prognostic Index (IPI) score ≥3 at the time of relapse preceding CART19, HGBL classification, no history of indolent lymphoma (IL), MYC rearrangement (-R) and double hit lymphoma (DHL) as predictive of disease progression at 2y; however, none of these characteristics remained predictive on multivariate analysis. Additionally, IPI score ≥3 at the time of relapse preceding CART19, HGBL classification, no history of IL, MYC-R and DHL were also predictive of death at 2y on univariate analysis; however, none of these characteristics remained predictive on multivariate analysis. Conclusions Tumor characteristics, including recurring genetic mutations as detected by CLMA, may not independently predict for survival outcomes for DLBCL/HGBL pts following receipt of CART19. However, our finding that TNFRSF14 mutations predict for a lower rate of disease progression at 2y on univariate analysis may be explained by loss of the inhibitory effect of HVEM on T helper cells through binding of B and T lymphocyte attenuator (BTLA) (Cell. 2016 Oct 6;167(2):405-418.e13). Additionally, our finding that TP53 mutations did not predict for inferior PFS following receipt of CART19 is in agreement with that of a prior analysis (J Clin Oncol. 2022 Feb 1;40(4):369-381). Performance of CLMA on a larger number of tumor samples from DLBCL/HGBL pts subsequently treated with CART19, which is planned, may be informative.

Durable MRD and Imaging-Negative Remission ≥ 5 Years Post-Therapy Predicts Long-Term Progression-Free Survival in Multiple Myeloma Patients - a Single-Center Observational Study

Introduction With the advent of modern multiple myeloma (MM) therapies, a significant proportion of patients can achieve durable clinical remission. Minimal residual disease (MRD) reflects depth of response and is a powerful predictor of progression-free survival (PFS) (Munshi et al, JAMA Oncology 2017). Although sustained MRD negativity (defined by IMWG as MRD-negative on two occasions, minimum one-year apart) is associated with improved PFS, there is continued long-term relapse in these patients. A recent study reported a 10-year PFS of 88% in MM patients who are MRD-negative &amp;gt; 3 years after total therapy (Mohan et al, Blood Advances 2022). In the current era of regular MRD testing in MM care, we aimed to estimate the 10-year PFS of unselected MM patients who are MRD and imaging-negative ≥ 5 years after latest therapy, using our single-center data. Methods MRD testing was introduced for MM patients in remission at the Icahn School of Medicine at Mount Sinai (ISMMS) in 2017. Therefore, we systematically reviewed all patients with MRD results in the ISSMS MM registry between July 2017 and December 2022. Next-generation multi-parametric flow cytometry (NGF) was used to detect MRD from 2017 to 2021, with the addition of next-generation sequencing (NGS) from 2021 onwards. MRD-negativity was defined as &amp;lt;1 in 10 5 by NGF or &amp;lt;1 in 10 6 by NGS, and one representative MRD result per year was taken for analysis. Whole-body positron emission tomography (PETCT) and MRI were used to evaluate bone or extra-medullary (EM) disease. Detailed retrospective chart review of patients with sequential MRD-negative results was conducted to identify those with durable clinical, MRD, and imaging negative remission. PFS was evaluated using Kaplan-Meier curves and survival estimates. Results Between 2017 and 2022, 1703 MM patients underwent MRD testing at our center. Of these patients, we have so far identified 92 patients who were in CR, MRD and imaging-negative ≥ 5 years after the start of latest therapy. The estimated 10-year PFS in our cohort was 91.4% (95% CI [0.833 ,1]; Figure 1). With a median follow-up time of 5.9 years (4.6 to 12.6 years), the majority of our cohort (75%) were off-therapy at last follow-up with a median time-off-therapy of 2.5 years. In terms of baseline patient and disease characteristics (Table 1), 57.6% patients were white and 60.9% were male. Most patients were ISS stage I (51.1%) with standard-risk cytogenetics (78.2%) at diagnosis. A much smaller proportion of our cohort had any adverse cytogenetics, including gain1q (13%) and del17p or TP53 mutation (7.6%). The majority of patients were in their first remission after frontline therapy (52.2%), with 33.7% having received autologous stem cell transplant (ASCT) first-line. A smaller proportion of the cohort had received salvage treatment; 31.5% had received two lines, 16.3% had received ≥ 3 lines. Four patients relapsed in this cohort (4.3%) and one patient died of a non-MM related cause. Of the patients who progressed, 2 relapsed with isolated biochemical disease and 2 with predominantly EM disease. Both biochemical relapses were preceded by conversion to MRD positivity by NGF 6 months to 1 year prior, whereas those relapsing with EM disease remained MRD negative. Three patients had been off-treatment between 1 to 4 years prior to clinical relapse and the fourth patient progressed whilst on maintenance treatment. Conclusion We report single-institution MRD data on unselected MM patients who have durable MRD and imaging-negative remission for at least 5 years from their latest line of therapy. The estimated 10-year risk of disease-progression in our cohort is around 8.6%, with the majority of patients being off-therapy. The low rate of disease-progression at 10 years demonstrates that a proportion of MM patients do not suffer multiple relapses and may therefore be potential candidates for discontinuation of maintenance. From our data, these patients are more often ISS stage I, have standard risk cytogenetics and achieve deep responses to frontline therapy. A smaller proportion of patients are able to achieve this landmark even after salvage therapies. This may be increasingly possible in the era of monoclonal antibodies and T cell redirection therapies. Analysis of larger real-world MM cohorts is needed to elucidate whether sustained MRD-negative remission at 5 years can truly predict long-term disease-free survival and possible cure.

Allogeneic Transplant for CLL Richter's Transformation: Single Center Retrospective Analysis

Introduction: Richter transformation (RT) describes the emergence of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). The prognosis is poor, with a median overall survival (OS) of 10 months. Treatment of RT is still challenging despite the availability of novel agents, and stem cell transplant (SCT) is commonly used as a consolidation strategy. Data on outcomes post-allogeneic-SCT for RT is limited. The OS on these reports' ranges from 41 to 75%. Methods: We conducted a retrospective study of patients diagnosed with RT at our center who underwent allogeneic SCT between 2005 and 2022. We evaluated predictors of outcome using Cox's proportional hazards regression analysis for overall and progression-free survival (PFS) and Fine and Grey regression for disease progression and non-relapse mortality (NRM). Results: 88 patients were identified, 85 had a diffuse large lymphoma histology and 3 Hodgkin's lymphoma. The median age was 61 years (range 25-74), and the majority (n=61, 69%) of patients were in complete response (CR, N=21) or partial response (PR, N=40) pre-SCT. Median follow-up among survivors was 74 months (range: 8-168); all outcomes are reported at 6 years. Overall, OS was 45% (95% CI: 34-56), and PFS 32% (95% CI: 22-43). The cumulative incidence of disease progression was 41% (95% CI: 31-53) and NRM 25% (95% CI: 17-36). In the univariate analysis, response prior to transplant was the most significant predictor of disease progression, OS, and PFS. Patients in CR/PR had a lower rate of disease progression (32% vs. 61%, HR: 0.2, 95% CI 0.2-0.6, p=0.002) and higher OS (59% vs 16%, HR: 0.3, 95% CI 0.2-0.5, p&amp;lt;0.001, Figure) and PFS (44% vs. 6%, HR: 0.2 (0.1-0.4), p&amp;lt;0.001) compared with those advanced (&amp;gt;CR2)or progressive disease. In addition, the presence of deletion 17p (del17p) or TP53 mutation was associated with a higher rate of disease progression (HR=3.1, 95% C 1.3 -7.3, p=0.01), but not with PFS or OS. The use of reduced intensity regimens resulted in favorable OS (HR=0.5, 95% CI 0.3-1.0, p=0.05) as compared to non-myeloablative conditioning. Age, HCT-CI score, donor type, donor-to-recipient gender, cell source, and graft-versus-host disease prophylaxis, or the presence of other cytogenetic abnormalities were not significantly associated with OS, PFS, disease progression, or NRM. There was also no advantage for any outcome when comparing individuals who achieved CR versus PR pre-SCT. The independent predictive value of CR/PR was confirmed in multivariate analysis for OS (HR=0.3, 95% CI 0.2-0.5, p&amp;lt;0.001) and disease progression (HR=0.4, 95% CI: 0.2-0.8, p=0.01), after adjusting for conditioning intensity for OS and deletion 17p (del17p) or TP53 mutation for disease progression. Discussion: In this single center series of patients treated with allogeneic SCT as consolidation for RT, disease status prior to SCT (CR/PR) emerged as a strong independent predictor of outcomes. The influence of tumor burden prior to SCT may be related to disease biology (e.g., patients not in CR/PR may have more aggressive RT) or may be related to decreased graft-versus-lymphoma effect. Based on our findings, we recommend that aggressive control of the disease with the goal of achieving a CR or PR should be attempted before allogeneic stem cell transplantation in patients with Richter transformation.

Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status.

Background: During active surveillance (AS), serum thyrotropin (TSH) levels may affect papillary thyroid microcarcinoma (PTMC) progression. We investigated AS outcomes according to whether levothyroxine (LT4) treatment was administered. Patients and Methods: From 2005 to 2019, 2896 patients with low-risk PTMC underwent AS. Of these, 2509 patients were included: 2187 patients did not receive LT4 at diagnosis (group I), 1935 patients did not receive LT4 during AS (group IA), and 252 patients started LT4 during AS (group IB). The remaining 322 patients were administered LT4 before or at diagnosis (group II). The tumor volume doubling rate (TVDR) and tumor size based on ultrasound examination results and time-weighted detailed TSH scores were calculated. Disease progression was defined as tumor enlargement ≥3 mm and/or the appearance of novel lymph node metastasis. Results: At diagnosis, group II had more high-risk features, such as younger age and larger tumors, than group I. However, group II had a lower disease progression rate (2.9% at 10 years) than group I (6.1%) (p = 0.091). The disease progression rate of group IB (13.8% at 10 years) was significantly higher than that of groups IA (5.0%) and II (2.9%) (p < 0.01). The TVDR of group IB before LT4 administration was significantly higher than that of groups IA and II (0.095 per year, -0.0085 per year, and -0.057 per year, respectively; p < 0.01), suggesting that patients with progression signs during AS were selectively prescribed LT4. The time-weighted detailed TSH score of group IB significantly decreased after LT4 administration compared with those before administration (3.35 and 3.05, respectively; p < 0.01). The TVDR also decreased from 0.13 per year to 0.036 per year (p = 0.08). The proportions of patients with rapid or moderate growth decreased significantly after LT4 (from 26.8% to 12.5%, p < 0.01). A multivariable analysis revealed group IB status was independently associated with disease progression (odds ratio [OR] = 3.42 [CI 2.15-5.44], p < 0.01), whereas age ≥40 years and <60 years and age ≥60 years were independently negatively associated with this outcome (OR = 0.23 [CI 0.14-0.38, p < 0.01 and OR = 0.16 [CI 0.10-0.27], p < 0.01). Conclusion: LT4 treatment may be associated with decreased tumor growth during AS of PTMC, but further confirmatory research is needed.

UGT1A1 *28/*28 genotype and risk of toxicity and disease progression in breast cancer patients treated with sacituzumab govitecan-hziy.

1033 Background: In metastatic and locally recurrent breast cancer the antibody drug conjugate, sacituzumab govitecan-hziy (SG), is approved as a second-line therapy in triple negative disease and a third-line therapy and beyond for ER+, endocrine resistant disease. UGT1A1 metabolizes the SN-38 payload of SG, and polymorphisms of the gene can lead to decreased enzyme activity and increased toxicity. We sought to determine if patients who were homozygous for the UGT1A1*28 allele polymorphism (*28/*28) experienced increased toxicity and a lower rate of disease progression when treated with SG. Methods: To evaluate the association of the *28/*28 genotype with the competing endpoints of Discontinuations for Disease Progression, Toxicity, and Futility, this pilot study undertook a single-center, retrospective chart review of breast cancer patients who received SG at City of Hope. Eligible subjects included breast cancer patients who received at least one dose of SG, had a known UGT1A1 status, and were followed for toxicity and disease progression. Data collection and analysis included reasons for discontinuing SG, onset of adverse effects, UGT1A1 status, age, gender, race and ethnicity, prior lines of therapy, and tumor receptor status. Results: Between July 2020 and September 2022, 67 women and 1 man underwent UGT1A1 testing prior to initiation of SG; the median age was 57.8 years, 75.0% had triple negative disease, and SG was given as a median third line of therapy. Seventeen (25%) patients were homozygous for *28 and 24 (35.3%) were heterozygous. Notably relating race and genotype, all 7 self-reported Black subjects were either carriers or homozygous for *28; there were no Black wildtype subjects. Most subjects were followed until Discontinuation for Disease Progression (55.9%), Toxicity (8.8%), or Futility (5.9%). Alternatively, 4.4% of subjects were lost to follow-up and 1 subject halted treatment due to cancer remission. The remaining 23.5% of subjects still took SG by the close of study in November 2022. On competing risk analysis comparing the wildtype group, *28/*28’s association with increased Discontinuation for Toxicity, was confirmed with a Hazards Ratio of 5.52 (95% confidence interval [CI] 1.15-26.49, p = 0.03). In contrast, Discontinuation for Disease Progression was unassociated to *28/*28 status in comparison to the wildtype group with a Hazards Ratio of 0.80 (95% CI 0.39-1.65, p = 0.54). Conclusions: Despite the relatively small sample size, 25% of patients had the *28/*28 genotype. We confirmed that *28/*28 is associated with a higher risk for discontinuation of SG for toxicity without an association to disease progression based on mutation status. Early UGT1A1 testing as standard practice may identify patients at risk for excess toxicity, who may undergo early dose reductions to prevent discontinuation of this important advanced breast cancer treatment.

Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance–Like Phenotype in Patients With Monoclonal Gammopathies

The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.

Remdesivir Alone or in Combination with Monoclonal Antibodies as an Early Treatment to Prevent Severe COVID-19 in Patients with Mild/Moderate Disease at High Risk of Progression: A Single Centre, Real-Life Study.

Early treatment with antivirals against SARS-CoV-2 infection can prevent the onset of severe COVID-19 in fragile and immunocompromised patients. In this real-life, prospective, observational study, we evaluated efficacy and safety of a 3-day early treatment with remdesivir in adult and fragile patients with a diagnosis of SARS-CoV-2 infection who referred to the COVID-19 early treatment service of Infectious Diseases Unit of University of Naples Federico from 10 January 2022 to 31 March 2022. The included patients could be treated with either remdesivir alone or with remdesivir plus a monoclonal antibody with activity against SARS-CoV-2. Among the 62 included patients, we showed low rates of hospitalization (8%), increase in oxygen supplementation (3.2%), ICU admission (1.6%) and death (1.6%). The rate of disease progression was 8% and it was similar in patients treated with remdesivir alone or in combination with monoclonal antibodies (6.7% and 9.4%, respectively; p = 0.531). The rate of adverse drug reaction was low and similar in the two groups (13.3% in patients treated with remdesivir, 15.6% in patients treated with the combination; p = 0.543). Most common adverse events were headache and fever. In conclusion, in our cohort of patients at a high risk of worse COVID-19 outcomes, an early course of remdesivir showed low rates of disease progression and adverse drug reactions.

SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematologic malignancies. Alloreactivity after HSCT is known to be mediated by adaptive immune cells expressing rearranging receptors. Recent studies demonstrated that the innate immune system could likewise sense the non-self signals and subsequently enhance the alloimmune response. We recently demonstrated that the donor/recipient mismatch of signal regulatory protein α (SIRPα), an immunoglobulin receptor exclusively expressed on innate cells, is associated with a higher risk of cGVHD and relapse protection in a cohort of acute myeloid leukemia patients who underwent allo-HSCT. Whether these effects also occur in other hematologic malignancies remains unclear. In the present study, we compared outcomes by SIRPα match status in a cohort of 310 patients who received allo-HSCT from an HLA matched-related donor for the treatment of lymphoid malignancies. Multivariable analysis showed that SIRPα mismatch was associated with a significantly higher rate of cGVHD (hazard ratio [HR] 1.8, P= .002), cGVHD requiring systemic immunosuppressive therapy (HR 1.9, P= .005), a lower rate of disease progression (HR 0.5, P= .003) and improved progression-free survival (HR 0.5, P= .001). Notably, the effects of SIRPα mismatch were observed only in the patients who achieved >95% of donor T-cell chimerism. The mismatch in SIRPα is associated with favorable relapse protection and concurrently increased risk of cGVHD in patients who undergo allo-HSCT for lymphoid malignancies, and the optimal donor could be selected based on the finding of the study to mitigate the risk of GVHD and relapse.

Volumetric Analysis of Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting the Response to Chemotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer.

We aimed to prospectively investigate intravoxel incoherent motion parameters to predict the response to chemotherapy in locally advanced non-small cell lung cancer (NSCLC) patients. From July 2016 to March 2018, 30 advanced NSCLC patients were enrolled and underwent chest intravoxel incoherent motion-diffusion-weighted imaging at Siemens 3T magnetic resonance imaging before and at the end of the first cycle of chemotherapy. Regions of interest were drawn including the whole tumor volume to derive the apparent diffusion coefficient value, D, D*, and f, respectively. Time-dependent receiver operating characteristic curves were generated to evaluate the cutoff values of continuous variables. A Cox proportional hazards model was used to assess the independent predictors of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were generated. Among the 30 patients, 28 cases (93.3%) died and 2 cases (6.7%) survived till the closeout date. Univariate Cox regression analyses revealed that the significant predictors of PFS and OS were the tumor size reduction rate, the change rates of D and apparent diffusion coefficient values, and the D value before therapy (PFS: P = 0.015, hazard ratio [HR] = 2.841; P < 0.001, HR = 5.840; P = 0.044, HR = 2.457; and P = 0.027, HR = 2.715; OS: P = 0.008, HR = 2.987; P < 0.001, HR = 4.357; P = 0.006, HR = 3.313; and P = 0.013, HR = 2.941, respectively). Multivariate Cox regression analysis suggested that △D% was identified as independent predictors of both PFS and OS (P = 0.003, HR = 9.200 and P = 0.016, HR = 4.617). In addition, the cutoff value of △D% was 21.06% calculated by receiver operating characteristic curve analysis. In the Kaplan-Meier analysis, the PFS and OS were significantly greater in the group of patients with △D% larger than 21.06% (log-rank test, χ2 = 16.453, P < 0.001; χ2 = 13.952, P < 0.001). Intravoxel incoherent motion-diffusion-weighted imaging was preferred for predicting the prognosis of advanced NSCLC patients treated with chemotherapy. A D increase more than 21.06% at 1 month was associated with a lower rate of disease progression and death.

Management, Surveillance Patterns, and Costs Associated With Low-Grade Papillary Stage Ta Non–Muscle-Invasive Bladder Cancer Among Older Adults, 2004-2013

Low-risk non-muscle-invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality; however, patients with low-risk NMIBC may often receive non-guideline-recommended and potentially costly surveillance testing and treatment. To describe current surveillance and treatment practices, cancer outcomes, and costs of care for low-grade papillary stage Ta (low-grade Ta) NMIBC and identify factors associated with increased cost of care. This population-based cohort study identified 13 054 older adults (aged 66-90 years) diagnosed with low-grade Ta tumors in the Surveillance, Epidemiology and End Results-linked Medicare database from January 1, 2004, through December 31, 2013. Medicare claims data through December 31, 2014, were also reviewed. Data were analyzed from April 1 to October 6, 2021. Surveillance testing and treatment among patients with low-grade Ta NMIBC. The primary outcome was patterns in population-level surveillance and treatment practice over time among patients with low-grade Ta NMIBC. Secondary outcomes were recurrence (defined as receipt of subsequent transurethral resection of bladder tumor >3 months after index diagnosis of NMIBC and initial transurethral resection of bladder tumor), progression (defined as receipt of definitive treatment for bladder cancer), and costs of care. Among 13 054 patients who met inclusion criteria, 9596 (73.5%) were male and 3458 (26.5%) were female, with a median age of 76 years (IQR, 71-81 years). A total of 403 patients (3.1%) were Black, 120 (0.9%) were Hispanic, 12 123 (92.9%) were White, and 408 (3.1%) were of other races and/or ethnicities. Rates of surveillance cystoscopy increased over the study period (from 79.3% in 2004 to 81.5% in 2013; P = .007), with patients receiving a median of 3.0 cystoscopies per year (IQR, 2.0-4.0 per year). Rates of upper tract imaging (particularly computed tomography or magnetic resonance imaging) also increased over the study period (from 30.4% in 2004 to 47.0% in 2013; P < .001), with most patients receiving a median of 2.0 imaging tests per year (IQR, 1.0-2.0 per year). The use of urine cytologic testing or other urine biomarker assessment also increased (from 44.8% in 2004 to 54.9% in 2013; P < .001). Rates of adherence to current guidelines were similar over time (eg, a median of 4398 patients [55.2%] received ≤2 cystoscopies per year in 2004-2008 vs a median of 2736 patients [53.8%] in 2009-2013; P = .11), suggesting overuse of all surveillance testing modalities. With regard to treatment, 2250 patients (17.2%) received intravesical bacillus Calmette-Guérin, and 792 patients (6.1%) received intravesical chemotherapy (excluding receipt of a single perioperative dose). Among all patients with low-grade Ta NMIBC, 217 (1.7%) experienced disease recurrence and 52 (0.4%) experienced disease progression. The total annual median costs of low-grade Ta surveillance testing and treatment increased by 60% (from $34 792 in 2004 to $53 986 in 2013), with higher 1-year median expenditures noted among those with disease recurrence ($76 669) vs no disease recurrence ($53 909) at the end of the study period. In this cohort study, despite low rates of disease recurrence and progression, rates of surveillance testing increased during the study period. The annual cost of care also increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overuse of surveillance testing and treatment, may mitigate associated increasing costs of care.

Management, surveillance patterns, and costs associated with low-grade papillary (Ta) nonmuscle-invasive bladder cancer.

464 Background: Low-risk non-muscle invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality, however, these patients may often receive non-guideline recommended and potentially costly surveillance and treatment(s). We sought to describe current surveillance and treatment practices, oncologic outcomes, and cost of care for low-grade papillary (LG Ta) NMIBC and identify predictors of increased cost of care. Methods: This population-based cohort study identified 13,054 patients diagnosed with LG Ta tumors in the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2004 through December 31, 2013. The primary outcome was to characterize trends in population-level surveillance and treatment practice patterns over time among LG Ta patients. The secondary outcomes were recurrence, progression, and costs of care. Results: Of the 13,054 patients who met inclusion criteria, 9,596 (73.5%) were male and 3,485 (26.5%) were female, with a median age of 76 (Interquartile Range (IQR): 71–81) years. Rates of surveillance cystoscopy increased over the study period (79.3% to 81.5%, p = 0.007) with patients undergoing a median of three cystoscopies per year (IQR: 2–4). Rates of upper tract imaging utilization also increased, namely the use of computed tomography (CT) or magnetic resonance imaging (MRI) (30.4% to 47%, p &lt; 0.001), with most patients undergoing a median of two imaging tests per year. Similarly, the use of urine cytology or other urine biomarkers also increased (44.8% to 54.9%, p &lt; 0.001). Rates of compliance with current guidelines decreased over time suggesting overutilization of all surveillance testing modalities. A total of 17.2% of patients received intravesical bacillus-Calmette Guerin (BCG) and 6.1% received intravesical chemotherapy (excluding single perioperative dose). Among all LG Ta patients, 1.7% and 0.4% experienced disease recurrence and progression, respectively. Total annual median costs of LG Ta surveillance and care increased 1.6-fold from $34,792 to $53,986 over the study period, with increased expenditures noted among those with disease recurrence ($53,909 and $76,669). Conclusions: Despite low rates of disease recurrence or progression, rates of surveillance testing increased during the study period. Annual cost of care increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overutilization of surveillance testing and overtreatment, may mitigate associated rising costs of care.

Clinical Efficacy of Atorvastatin Combined with Ezetimibe in Preventing Restenosis after Coronary Artery Bypass Grafting

To investigate the clinical efficacy of atorvastatin combined with ezetimibe in preventing restenosis after coronary artery bypass grafting. Total 100 patients in Tangshan Workers’ Hospital were randomly divided into observation group and control group. The control group received 100 mg aspirin, 75 mg clopidogrel and atorvastatin 20 mg once a day. The observation group was given 10 mg ezetimibe once a day in addition to the above drugs. The venous diameter, blood lipid level changes, inflammatory response, quality of life, adverse reactions and treatment effects were assessed. After treatment for 6 mo, hypersensitive C-reactive protein and interleukin-6 levels were lower in observation group than control group. Total cholesterol, triglyceride and low-density lipoprotein cholesterol levels were lower and high-density lipoprotein cholesterol level was higher in observation group than control group. The observation group exhibited higher rates of vein garft stenosis improvement, lower rates of disease progression, lower incidence of major adverse cardiovascular events and higher 36-Item Short-Form Health survey scores than control group. The efficacy of ezetimibe combined with atorvastatin in treating restenosis after coronary artery bypass grafting is good, which also controls blood lipids with low incidence of adverse reactions.

SC266 - Association between previous negative biopsies and lower rates of disease progression during active surveillance for prostate cancer

SC266 - Association between previous negative biopsies and lower rates of disease progression during active surveillance for prostate cancer

Role of ivermectin in prophylaxis and treatment of Covid-19 patients: A systematic review

For a systematic review, the present study made an extensive review around the formulated question by identifying, selecting and critically appraising data based on a comprehensive and reproducible search strategy. It was found that there exists a significant literature which speaks positively about the role of Ivermectin in prophylaxis. The drug has been found statistically significant in mortality reduction, clinical recovery time and viral clearance. Contrary to what the WHO has claimed, Ivermectin prophylaxis was associated with a very low rate of disease progression.