Inferior Overall Survival Research Articles

Autologous Stem Cell Transplant in Fit Patients With Late Relapsed Diffuse Large B-Cell Lymphoma That Responded to Salvage Chemotherapy

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan–Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1–3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 yr (range 19–78), and 36 (24%) patients were of ≥70 yr. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70–78 yr), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 versus 124.7 months, P = .045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 versus 61.4 months, P < .0001) and OS (17.8 versus 111.7 months, P = .0004). There was no statistically significant difference in survival in patients who achieved PR versus CR, though numerically inferior in the former, with median PFS of 38.9 versus 59.3 months (P = .23) and median OS of 78.3 versus 111.7 months (P = .62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70 to 78 yr at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Association of potentially inappropriate medications with prognosis among older patients with non-small cell lung cancer

BackgroundPotentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC.MethodsIn this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS).ResultsWe finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01–1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11–3.14; P = 0.020; respectively).ConclusionsPIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs.

DIPG-77. SOMATICTP53,PIK3R1, NF1 ORTERT MUTATIONS ARE ASSOCIATED WITH INFERIOR CLINICAL OUTCOME IN H3K27M-ALTERED DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND H3K27-altered diffuse midline gliomas (DMGs) have poor prognosis with no standard of care therapy beyond radiation (RT). While RT prologues survival, not all patients respond. Prior work has shown somatic TP53 mutations predict radiation resistance, and poorer outcomes. We report on a multi-center retrospective cohort study to identify molecular biomarkers of RT response in DMG patients. METHODS We performed retrospective chart reviews of patients with biopsy-proven H3K27M-altered DMG between 2013-2023 from six US medical centers and the DMG Center in Zurich. Patients with tumor genomic sequencing and completion of RT were eligible. Genomic alterations were evaluated for somatic mutations, fusions, and chromosomal instability. Cox proportional hazard models were used to evaluate associations between genomic alterations and survival. Multivariate analysis included all significant variables at P &amp;lt;0.1 in initial analysis, including age at diagnosis, tumor location, TP53 and PIK3R1 alterations. RESULTS 297 patients (135 female; median age 8.3years; range 0.2-71.4 years) were included. Median progression-free survival (PFS) and overall survival (OS) was 7.6months (95%-CI 6.9-8.6) and 14.0months (95%-CI 12.9-15.7). Univariate analysis identified TP53 or PIK3R1 status to be associated with shorter OS (TP53-mutant 12.5months vs. TP53-wildtype 17.5months; HR=1.5; 95%-CI (1.1-2.0), P=0.005); (PIK3R1-mutant 12.6months vs. PIK3R1-wildtype 14.5months; HR=1.9, 95%-CI (1.1-3.4), P=0.03). Multivariate analysis corroborated TP53 status association with shorter OS (HR=1.5; 95%-CI (1.2-2.0), P=0.003). Subgroup univariate analysis of pontine DMG patients showed reduced OS with TP53, NF1, or TERT mutations (TP53-mutant 11.9months vs. TP53-wildtype 15.2months; HR=1.6; 95%-CI (1.1-2.3), P=0.02); (NF1-mutant 8.4months vs. NF1-wildtype 13.6months; HR=2.3; 95%-CI (1.1-5.0), P=0.03); (TERT-mutant 8.5months vs. TERT-wildtype 13.6months; HR=2.5; 95%-CI (1.1-5.7), P=0.03). Subsequent multivariate analysis corroborated the association of TERT mutations with shorter OS in pontine DMG (HR=2.5; 95%-CI (1.05, 5.9), P=0.03). CONCLUSIONS This is one of the largest molecular characterized cohorts of H3K27M-altered DMG patients. DMGs with somatic TP53 or PIK3R1 mutations demonstrate inferior OS. Pontine DMG patients with somatic TP53, NF1 or TERT mutations demonstrate inferior OS.

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

Superiority of BM over PBSC for recipients with pre-transplant lung dysfunction in HLA-matched allogeneic HCT

Background aimsPre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction. MethodsWe analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs. bone marrow (BM) in two cohorts based on the presence of a lung score by the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI): the Lung-scored (LS) and non-LS cohorts. ResultsIn the LS cohort, the 2-year overall survival (OS) in the BM group tended to be higher than that in the PBSC group (72.4% vs. 61.4%; P = 0.044). In the non-LS cohort, there was no significant difference between the two groups (71.7% vs. 73.2%; P = 0.13). Multivariate analyses confirmed that PBSC was significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.66; 95% CI, 1.09-2.54; P = 0.019). On the other hand, the cell source did not affect OS in the non-LS cohort (HR, 0.92; 95% CI, 0.76-1.12; P = 0.41). We found that PBSC was associated with an increased risk of NRM in the LS cohort (HR, 2.17; 95% CI, 1.16-4.05; P = 0.016), while the cell source did not significantly affect NRM in the non-LS cohort. PBSC was not identified as a risk factor for relapse in either cohort. ConclusionsOur results suggest that BM might be beneficial for recipients with lung dysfunction in HLA-matched allo-HCT.

Survival of patients with ruptured gastrointestinal stromal tumour treated with adjuvant imatinib in a randomised trial

BackgroundPatients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival.MethodsWe explored recurrence-free survival (RFS) and overall survival (OS) of patients with ruptured GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 patients with high-risk GIST were allocated to adjuvant imatinib for either 1 year or 3 years after surgery. Of the 358 patients with confirmed localised GIST, 73 (20%) had rupture reported. The ruptures were classified retrospectively using the Oslo criteria.ResultsMost ruptures were major, four reported ruptures were reclassified unruptured. The 69 patients with rupture had inferior RFS and OS compared with 289 patients with unruptured GIST (10-year RFS 21% vs. 55%, OS 59% vs. 78%, respectively). Three-year adjuvant imatinib did not significantly improve RFS or OS of the patients with rupture compared with 1-year treatment, but in the largest mutational subset with KIT exon 11 deletion/indel mutation OS was higher in the 3-year group than in the 1-year group (10-year OS 94% vs. 54%).ConclusionsAbout one-fifth of ruptured GISTs treated with adjuvant imatinib did not recur during the first decade of follow-up. Relatively high OS rates were achieved despite rupture.Clinical Trial RegistrationNCT00116935.

Longitudinal circulating tumor DNA (ctDNA) analysis during treatment (Tx) of locally advanced resectable (LAR) gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ADENOCA): The PLAGAST prospective biomarker study.

4028 Background: After surgery, patients (pts) with LAR G/GEJ ADENOCA have a high recurrence risk despite Tx. Here, we investigate the ability of ctDNA to predict Tx response and improve risk stratification in a sub-cohort of pts from the PLAGAST prospective study (NCT02674373). Methods: Plasma samples were prospectively collected at baseline (before neoadjuvant therapy (NAT)/before surgery for NAT-naive pts), during-NAT, post-NAT, and post-surgery within 2-12 weeks, before adjuvant Tx [molecular residual disease (MRD) window]. Retrospective ctDNA analysis was performed using a clinically validated personalized, tumor-informed 16-plex PCR assay (Signatera, Natera Inc.). ctDNA results were evaluated for their correlation to recurrence-free survival (RFS) and overall survival (OS). Results: Between 07/2015 and 12/2022,plasma samples (n=283) were collected from 63 pts with LAR (≥cT2 and/or cN+), G (N=38/63; 60%) and GEJ (N=25/63; 40%) ADENOCA, median (m) age: 66 years (range: 34-86), and mfollow-up: 31 months (mo) (range: 2-93). ctDNA-clearance from baseline to during-NAT (N=30) or post-NAT (N=28), and MRD (N=50) window was associated with longer RFS and OS. Persistent ctDNA positivity (+ve) during-NAT was associated with a mRFS of 13.3mo vs. not reached (NR) for pts who achieved ctDNA-clearance (HR=4; p=0.032), and a mOS of NR for both groups, with 24mo OS rate at 95.6% vs. 58.6% (HR=5.85; p=0.097), respectively. ctDNA clearance post-NAT was associated with a mRFS of 7.79 vs. 52.04 mo (HR= 3.69; p=0.019) and a mOS of 18.9mo vs. NR (HR=8.78; p=0.007) for ctDNA-cleared vs. pts who did not clear, respectively. During the MRD window, mRFS of 3.57mo vs. NR (HR=12.94; p&lt;0.0001) and mOS of 8.59mo vs. NR (HR=14.54; p&lt;0.0001) was observed for ctDNA+ve and ctDNA negative pts, respectively. ctDNA dynamics revealed pts with early ctDNA clearance (during NAT) had the best outcomes, followed by pts who cleared ctDNA post-NAT, while pts who remained ctDNA+ve at baseline, during-NAT, and post-NAT had worse RFS and OS (24mo RFS rate of 75% vs. 48% vs. NR and 24mo OS rate of 100% vs. 80% vs. 17%, respectively). Of note, pts who achieved ctDNA clearance post-NAT correlated with tumor regression grade (TRG) 1/2/3 when compared to a TRG score of 4/5 in pts who were unable to clear ctDNA post-NAT (p=0.0345). Conclusions: Tumor-informed ctDNA results were predictive of NAT response and correlated with long-term outcomes with early ctDNA clearance associated with superior RFS and OS; meanwhile persistent ctDNA+ve post-NAT/pre-surgery/during MRD correlated with inferior OS and/or RFS as well as poor pathological response. In this initial analysis of the PLAGAST study, longitudinal ctDNA monitoring was prognostic of patient outcomes and may guide NAT clinical decision-making in pts with LAR G/GEJ ADENOCA. Clinical trial information: NCT02674373 .

Improving diversity in phase I oncology clinical trials: A single institution experience at the University of Colorado Cancer Center.

e13687 Background: Despite continued improvements in cancer outcomes, disparities persist between racial, ethnic, and socioeconomic groups. One potential driver is the lack of appropriate representation in clinical trials, including dose-finding studies. We implemented a set of initiatives including patient education, outreach, a Spanish-speaking bicultural clinic, and regular review of enrollment by race and ethnicity. To investigate the impact of these initiatives, we examined phase I clinical trial patient demographics and treatment outcomes before and after the intervention. Methods: We performed a retrospective review of patients enrolled in 2018-2019 (cohort 1[C1], pre- intervention) and 2022-2023 (cohort 2[C2], post-intervention). We collected patient demographics, area deprivation index (ADI), body mass index (BMI), ECOG performance status, and tumor type. Differences between cohorts were evaluated with T-tests, Chi-Square test, or the Fisher Exact test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Hazard ratios (HR), confidence intervals (CI) and p values were derived using the cox proportional hazards method. A multivariable model for patients with colorectal cancers (CRC) was selected using the Akaike information criterion (AIC). Results: A total of 361 patients (C1 n = 209, C2 n = 152) were included. Overall, 52.4% of patients were female. The most common tumor sites were CRC (18.3%), pancreas (11.9%) and breast (10.8%). Study participants were 85.0% White, 3.3% Asian, 1.4% Black and 9.1% Hispanic, compared to cancer incidence in Colorado of 92.8%, 1.6% and 3.3% and 10.0%, respectively. Following our intervention, there was an increase in language preference other than English from 1.9% (4/209) to 6.6% (10/152) (p = 0.028) and in translated consents from 1.4% (3/209) to 5.9% (9/152) (p = 0.033). There was no statistically significant difference in race, ethnicity, insurance, or tumor type, although there was a non-statistically significant increase in Hispanic patients from 8.1% to 10.5%. Median PFS improved from 1.9 to 2.8 months (HR = 0.72, 95% CI 0.57-0.90, p = 0.003). ECOG 1 v. 0 was associated with inferior OS (HR = 1.35, 95% CI 1.06-1.73, p = 0.017), and BMI ≥18.5 v. &lt;18.5 was associated with superior OS (HR = 0.59, 95% CI 0.37-0.95, p = 0.03). AIC model of CRC (n = 66) revealed that ADI scores of 6-10 were associated with worse PFS and OS (p = 0.022 and p = 0.001, respectively). Conclusions: Our interventions resulted in an increase in accrual of non-English speaking patients, however, there was not yet a statistically significant change in overall race and ethnicity. Our study confirms poorer clinical outcomes for patients with higher ADI scores. Further research and intervention are warranted to mitigate disparities in clinical trial accrual and improve clinical outcomes for disadvantaged patients.

Outcomes of very young women and adolescent (VYWAA) with breast cancer (BC) in rural and urban Saskatchewan: A population-based cohort study.

1571 Background: BC is uncommon in VYWAA (≤ 35 years) and accounts for about 1.8% of all BC. As BC screening is typically recommended for women aged 50-74 years there is a risk of delayed diagnosis of BC in VYWAA especially those with rural residence. The current study aims to assess outcomes of a cohort of VYWAA with BC in relation to their place of residence in the province of Saskatchewan over a period of 20 years. Methods: In this population-based retrospective cohort study all women ≤ 35 years with histologically documented epithelial BC during 2000-2019 were evaluated. Survival of the entire cohort and its subgroups was estimated using the Kaplan−Meier method, and the survival distribution of different groups was compared by the log rank test. A multivariate Cox proportional hazard model was performed. Various clinical and demographic variables were examined for their prognostic importance of overall survival (OS) for all stages and disease-free survival (DFS) for early-stage BC. Results: 248 eligible women with a median age of 32 years were identified, 24% were &lt;30 years of age. Of all patients, 51% had node positive disease, 7% had DCIS, 15% stage I, 42% stage II, 22% stage III and 11% had stage IV disease at initial presentation. Among them 42% had hormone receptor +, 28% had HER2 + and 23% had triple negative BC (TNBC).16% developed BC within 1-year of pregnancy. 53% were rural resident and 47% were urban resident. Significant differences were noted between the two groups regarding smoking history (42 vs. 25%), HER2+BC (35% vs. 20%) and mean platelet count (285 vs. 258). Median follow up for all women was 91 months with a total follow up period of 294 months. Median DFS of VYWAA with stage I to III disease has not reached. 10-year estimated DFS of all women was 66%. 10-year DFS for stage I and II was 73% and 75%, respectively, vs. 43% for stage III (p&lt;0.001). Median OS of entire cohort with stage 0-IV BC has not reached. 10-year OS of all VYWAA was 69%. 10 years OS of urban women was 79% compared to 65% for rural resident (p=0.041). 10-year OS of women age &gt;30 years was 74% compared to 62% for age 26-30 years and 55% for age &lt;26 (p=0.35).10 years OS of VYWAA with non-TNBC was 73% compared to 63% for with TNBC (p=0.028). On multivariate analysis for women with early-stage disease, stage III BC, HR, 3.0 (1.80-4.92) and grade III BC were significantly correlated with inferior DFS. On a multivariate analysis for OS of all VYWAA with stage 0 to IV disease, rural residence, HR, 1.75 (1.08-2.81); TNBC, HR, 2.25 (1.34-3.80), and stage IV disease, HR, 8.1 (4.72-13.94) were correlated with inferior OS. Conclusions: Very young women and adolescent with BC have a high incidence of node-positive disease and HER2+ and TNBC subtypes. TNBC and grade III disease were associated with inferior DFS in stage I-III disease whereas stage IV BC, TNBC and rural residence were correlated with inferior survival in women with stage 0-IV disease.

Myc rearrangement redefines the stratification of high-risk multiple myeloma.

Myc rearrangement (Myc-R) is a controversial factor linked to adverse outcomes in newly diagnosed multiple myeloma (NDMM). This study aimed to evaluate the impact of Myc-R on the prognosis of NDMM patients and its role in risk stratification compared with traditional high-risk cytogenetic abnormalities (HRCAs). A total of 417 NDMM patients enrolled from May 2009 to September 2022 were included. Fluorescence insitu hybridization (FISH) was used to detect Myc-R and other Myc abnormalities (Myc-OA). Median progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and log-rank tests. Multivariate Cox regression analysis was used to identify independent risk factors. Myc-R was identified in 13.7% of patients, while 14.6% had Myc-OA. Patients with Myc-R had significantly shorter median PFS (15.9 months) and OS (25.1 months) compared with those with Myc-OA (24.5 months PFS; 29.8 months OS) and Myc-negative (Myc-N) status (29.8 months PFS, 29.8 months OS). Myc-R was independently associated with worse PFS and OS compared to Myc-OA. Patients with Myc-R alone had inferior median PFS (15.9 months vs. 28.1 months, p = 0.032) and OS (25.1 months vs. 61.2 months, p = 0.04) compared to those with traditional single HRCA. The study suggests that traditional single HRCA may not significantly impact survival in NDMM patients. However, incorporating Myc rearrangement or traditional double/triple-hit HRCAs into the risk stratification model improves its predictive value, highlighting the importance of Myc rearrangement in risk assessment. Myc rearrangement is an independent adverse prognostic factor in NDMM. The incorporation of Myc rearrangement or multiple HRCAs into risk stratification models improves their prognostic value, providing a novel perspective on high-risk factors in NDMM.

Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Adult Acute Myeloid Leukemia: Outcomes and Prognostic Factors

Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS)/AML experiencing relapse after a first allograft (HCT1), but prognostic factors for outcomes are poorly characterized. To provide a detailed analysis of HCT2 outcomes and associated prognostic factors in a large single-center cohort, with a focus on identifying predictors of relapse and nonrelapse mortality (NRM), we studied adults ≥18 years who underwent HCT2 at a single institution between April 2006 and June 2022 for relapsed AML (n = 73) or MDS/AML (n = 8). With a median follow-up among survivors of 74.0 (range: 10.4 to 187.3) months, there were 30 relapses and 57 deaths, of which 29 were NRM events, contributing to the estimates for relapse, overall survival (OS), relapse-free survival (RFS), and NRM. Three-year estimates for relapse, RFS, and OS were 37% (95% confidence interval: 27% to 48%), 32% (23% to 44%), and 35% (26% to 47%). The rate of NRM at 100 days and 18 months was 20% (12% to 29%) and 28% (19% to 39%). Outcomes differed markedly across patient subsets and were substantially worse for patients who underwent HCT2 with active disease (ie, morphologic evidence of bone marrow and/or extramedullary disease), for patients who relapsed ≤6 months after HCT1, and for patients with higher HCT-specific Comorbidity Index (HCT-CI) or treatment-related mortality (TRM) scores. After multivariable adjustment, active disease was associated with a higher risk of relapse (hazard ratio [HR] = 3.19, P = .006) and shorter RFS (HR = 2.41, P = .008) as well as OS (HR = 2.17, P = .027) compared to transplant in morphologic remission without multiparameter flow cytometric evidence of measurable residual disease. Similarly, a relapse-free interval ≤6 months after the first allograft was associated with higher risk of relapse (HR = 5.86, P < .001) and shorter RFS (HR = 2.86; P = .001) and OS (HR = 2.45, P = .003). Additionally, a high HCT-CI score was associated with increased NRM (HR = 4.30, P = .035), and shorter RFS (HR = 3.87, P = .003) and OS (HR = 3.74, P = .006). Likewise, higher TRM scores were associated with increased risk of relapse (HR = 2.27; P = .024) and NRM (HR = 2.01, P = .001), and inferior RFS (HR = 1.90 P = .001) and OS (HR = 1.88, P = .001). A significant subset of patients with AML or MDS/AML relapse after HCT1 are alive and leukemia-free 3 years after undergoing HCT2. Our study identifies active leukemia at the time of HCT2 and early relapse after HCT1 as major adverse prognostic factors, highlighting patient subsets in particular need of novel therapeutic approaches, and supports the use of the HCT-CI and TRM scores for outcome prognostication.

1p and 1q: Partners in crime in multiple myeloma.

7571 Background: Cytogenetic abnormalities in multiple myeloma (MM) highly influence the disease course, response to treatment and survival. Trisomies and immunoglobulin H chain translocations are primary CA while del(17p), gain(1q), del(1p) among others are secondary CA. Gain (3 copies) and amplification (&gt;3 copies) 1q have been recognized as adverse prognostic markers and incorporated into the second revision of the International Staging System (R2-ISS). However, the role of del(1p) is less well defined, especially in the era of novel therapies. We aimed to analyze the outcomes of newly diagnosed MM (NDMM) patients with chromosome 1 abnormalities, mainly del 1p, treated with autologous stem cell transplant (ASCT) consolidation at our institution. Methods: We conducted a retrospective study of all NDMM patients who were treated with ASCT from 1/1/2015-2/13/2019 (n=511). High-risk cytogenetics (HRC) were defined by the presence of del(17p), t(4;14), or t(14;16) similar to R-ISS; standard-risk cytogenetics (SRC) were defined as the absence of HRC. Modified HR cytogenetics (mHRC) included gain/amp 1q and/or t(14;20) in addition to HRC, while ultra high-risk (uHRC) included 2 or more mHRC CA. Results: Of 511 pts transplanted, 453 had cytogenetic data at the time of diagnosis. SRC were seen in 353 pts (77.9%), while 100 (22.1%) had HRC, 156 (34.4%) had mHRC, and 43 (9.5%) had uHRC. Thirty-two (7.1%) pts had del(1p) while 105 (23.2%) had gain 1q and 30 (6.6%) had amplification 1q. As expected, compared to SRC pts, pts with HRC, mHRC and uHRC had higher risk of relapse or death. Patients with gain and amp 1q had inferior outcomes in terms of progression-free survival (PFS) (HR 1.35; 95% CI 1.06-1.73, p=0.016), time to next treatment (TTNT) (HR 1.84; 95% CI 1.40-2.42, p&lt;0.001) and overall survival (OS) (HR 1.47; 95% CI 1.06-2.02, p=0.02) compared to those without, consistent with published literature. The median PFS, TTNT and OS from ASCT in pts with gain/amp 1q were 3.17 years (y), 3.95y and 7.13y, respectively, compared to 4.01y, 7.60y and 8.21y in pts without gain/amp 1q. Pts with del(1p) had inferior PFS (median 2.43y versus 3.98y; HR 1.75; 95% CI 1.16-2.64, p=0.008), TTNT (median 2.72y versus 6.17y; HR 1.96; 95% CI 1.22-3.14, p=0.005) and OS (median 4.11y versus 8.38y; HR 2.19; 95% CI 1.34-3.58, p=0.002) from the time of ASCT compared to those without del(1p). Conclusions: In our study of NDMM patients that underwent AHCT, del(1p) at diagnosis was an independent predictor of shorter PFS, TTNT and OS. Despite induction therapy involving novel drugs and ASCT consolidation, patients with del(1p) at diagnosis continue to have inferior outcomes. Larger analyses are needed to validate the prognostic value of del(1p) and investigate its role in predicting outcomes in MM.

Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.

Abstract PS16-08: Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study

Abstract Background Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer that presents with high tumor stage and a poor prognosis. MpBC tumors tend to have worse outcomes compared to other non-metaplastic triple-negative breast cancers (TNBC). Although MpBC has been described as chemotherapy resistant, chemotherapy remains a mainstay of treatment. MpBC tumors can be further characterized by their specific histologic pattern. The existing literature on outcomes of MpBC by histologic pattern is limited, with varying results regarding response rate and overall survival (OS). Identifying a pattern of MpBC that has better response to treatment could help tailor treatment recommendations. Methods A retrospective chart review was performed and identified 106 patients with early-stage, high-grade MpBC who were diagnosed at Levine Cancer Institute between January 1, 2010 and September 1, 2021. A matched control cohort (n=106) of patients diagnosed with non-metaplastic TNBC was selected based on propensity score matching on diagnosis date, age at diagnosis, race, pathologic staging, and tumor grade. Patient demographics, tumor characteristics, therapeutic interventions, residual cancer burden (RCB), and outcomes were collected. The associations between the histologic patterns of MpBC and disease characteristics were evaluated using chi-squared tests for categorical variables and Wilcoxon tests for continuous variables. We also examined the differences in RCB scores between the MpBC cohort and the non-metaplastic TNBC cohort who received neoadjuvant chemotherapy. Additionally, Kaplan-Meier and Cox proportional hazard analysis was performed to assess differences in recurrence free survival (RFS) and OS between the spindle cell/sarcomatous pattern versus all other patterns. Results For the entire group (n=212), median age at diagnosis was 58 years (range, 24-92); all patients were female; 66% White, 29% Black, and 5% unknown race. Most tumors were triple-negative (91%); 19%, 56% and 14% with Clinical Stage I, II, and III disease, respectively. A total of 63% of patients underwent radiation treatment and 76% received chemotherapy (43% neoadjuvant and 57% adjuvant). Recurrence after treatment occurred in 16% of all patients. In the MpBC cohort (n=106), the histologic patterns included spindle cell/sarcomatous (34%), squamous (17%), heterologous mesenchymal (31%), mixed (17%), and other (1%). Of those with MpBC who received neoadjuvant chemotherapy (n=32), RCB among the different histologic patterns was assessed. When comparing spindle cell/sarcomatous versus the other histologic patterns combined, there was no significant difference in RCB (p = 0.81), although more RCB III scores were recorded in the spindle cell/sarcomatous pattern compared to the other MpBC patterns (40% versus 30%). When assessing RFS and OS by histologic pattern in the entire MpBC cohort, spindle cell/sarcomatous tumors had inferior RFS (p = 0.0194) and OS (p = 0.0039) compared to the other MpBC patterns combined. When comparing RCB values between MpBC and non-metaplastic TNBC, there were numerically more RCB-III classes in the MpBC cohort as compared to the non-metaplastic TNBC. Conclusion MpBC is an aggressive and difficult breast malignancy to treat. Based on our single institution review, no correlation between RCB and the histologic pattern of MpBC was found, however, RFS and OS were worse among the spindle cell/sarcomatous pattern. Furthermore, the MpBC cohort had numerically higher RCB-III scores than the TNBC control cohort, which is in line with historical data. Citation Format: Ashley Matusz-Fisher, Annabel Chen, Erin Donahue, Courtney Schepel, Michelle Wallander, Chad Livasy, Richard White, Antoinette Tan, Lejla Hadzikadic-Gusic. Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study [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 PS16-08.

Deciphering the Prognostic Significance of MYD88 and CD79B Mutations in Diffuse Large B-Cell Lymphoma: Insights into Treatment Outcomes.

The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt DLBCL patients. Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed. Potential molecular mechanisms were investigated through Gene Set Enrichment Analysis and xCell methodology. In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable progression-free survival (PFS) and overall survival (OS) compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt. However, in the non-MCD subtype, patients with MYD88-CD79Bco-mut exhibited significantly inferior OS than MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while there was no significant OS difference between MYD88/CD79Bsingle-mut and MYD88-CD79Bco-wt (median OS: 68.8 [95% CI 22-NA] vs NA [95% CI 112-NA] vs 177.7 [95% CI 159-NA]months; MYD88-CD79Bco-mut vs MYD88/CD79Bsingle-mut: p=0.02; MYD88-CD79Bco-mut vs MYD88-CD79Bco-wt: p=0.03; MYD88/CD79Bsingle-mut vs MYD88-CD79Bco-wt: p=0.33). Regarding patients with MYD88-CD79Bco-mut, there was no significant difference in PFS and OS between the MCD and non-MCD subtypes. Within the MYD88-CD79Bco-mut group, patients with PIM1mut had better PFS than PIM1wt (median PFS: 8.34 [95% CI 5.56-NA] vs 43.8 [95% CI 26.4-NA] months; p=0.02). Possible mechanisms contributing to the superior PFS of PIM1mut patients may include activated lymphocyte-mediated immunity and interferon response, a higher proportion of natural killer T cells and plasmacytoid dendritic cells, as well as suppressed angiogenesis and epithelial-mesenchymal transition, along with lower fibroblast and stromal score. In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.

Triple Positive Oral Squamous Cell Carcinoma Patients Predict Poor Survival Outcomes: Multiple Factor Positivity Warrants the Need for Modified Treatment Approaches.

The presence of lymphovascular invasion (LVI), perineural invasion (PNI) and extranodal extension (ENE) have shown adverse outcomes in oral squamous cell carcinoma (OSCC). This study evaluated the impact of LVI, PNI and ENE, individually and in combination, on survival outcomes in OSCC. A retrospective analysis of a prospectively maintained oral cancer database was done from January 2017 to March 2023. All consecutive OSCC patients who underwent curative intent surgery were included. The triple-positive group was defined by the presence of all three features (LVI/PNI/ENE), while the double-positive group had the presence of two features. The disease-free survival (DFS) and overall survival (OS) analysis was done between different study groups. A total of 255 patients were included in the analysis. The LVI, PNI and ENE positivity was 13%, 26% and 11%, respectively. There were 19 patients (7%) with double-positive and ten patients (4%) with triple-positive disease. The triple-positive group had lower DFS than non-triple-positive (0% vs 57%, p-value 0.001) and lower OS (0% vs 72%, p-value 0.003). The median DFS and OS of the triple-positive group were eight months and 24months, respectively. Similarly, the double-positive group also had statistically significant inferior DFS (p-value 0.007) and OS (p-value 0.002) compared to the single-positive/triple-negative group. The triple-positive disease had poor outcomes, with no patients achieving disease-free or overall survival at the 5-year follow-up. The presence of multiple adverse factors necessitates modification of adjuvant therapy and therapeutic strategy, which may enhance survival outcomes.

Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITDmut+ Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults ≥18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status: first complete remission (CR1), second or greater complete remission (≥CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, n = 2389; ≥CR2, n = 340; R/R, n = 418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with ≥CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (P = .003). In multivariable analyses, patients with a disease status of ≥CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], P = .0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at ≤2.6 months had better LFS compared with ≥CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a ≥CR2 or R/R disease status at ≤2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.

Early progression is associated with worse survival in patients with Waldenström’s macroglobulinemia

Early progression of disease within 24 months (POD24) of diagnosis is associated with inferior overall survival (OS) in follicular lymphoma, but its prognostic role in Waldenström’s macroglobulinemia (WM) is still unclear. Here, we performed a retrospective analysis of 373 patients pooled from the database of the Chinese Registration Network for WM (CRNWM) to determine the outcomes of early progressors. POD24 occurred in 98 evaluable patients (26.3%). The median OS in patients with POD24 was 40 months (95%CI: 15.2–64.0), which was significantly shorter than that without POD24 (156 months, 95%CI: 123.6–188.4; HR: 6.587, 95% CI 4.392–9.881, P < 0.0001). Moreover, subgroup analysis showed that POD24 still maintained its predictive ability of inferior OS in patients treated with rituximab or bortezomib-based treatment. Patients with a very high-risk rIPSSWM stage were more likely to have POD24 (P = 0.020). In conclusion, POD24 was associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10×albumin+0.05×ALC), respectively. The cutoff for low muscle mass was 43.0cm2/m2 for BMI below 25kg/m2 and 53.0cm2/m2 for BMI 25kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50days) was defined as (SMI after NACRT-SMI before NACRT)/interval (days)×50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65years. The primary outcome measure was overall survival (OS). During a median follow-up of 32.8months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3years, P=0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P=0.270 and P=0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3years, P<0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P<0.0001) in elderly patients, and 47.4% and 62.1% (P=0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P=0.008). EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.

Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi-institutional Study.

This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and seven with bulky N+. The median follow-up duration was 54.0 months (range, 6.4 to 162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS, and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 category, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.