Median Time To Next Treatment Research Articles

A retrospective observational study of ibrutinib in chronic lymphocytic leukaemia in a real-life setting in France using the national claims database (OSIRIS).

Ibrutinib is a Bruton's tyrosine kinase inhibitor indicated for the first-line treatment and relapse of chronic lymphocytic leukaemia (CLL), Waldenström's macroglobulinemia (WM) and mantle cell lymphoma (MCL). This study aimed to describe the characteristics of CLL patients treated with ibrutinib and its effectiveness, safety, and treatment pattern in real life. All patients covered by the general health scheme (approximately 80% of the French population) with a first ibrutinib dispensation from August 1, 2017 (date of reimbursement in France) to December 31, 2020, were identified in the French National Health Insurance database (SNDS). An algorithm was developed to identify the disease (CLL, MCL or WM) for which ibrutinib was prescribed. This article focused on CLL patients. The time to next treatment (TTNT) was plotted using Kaplan‒Meier curves. During this period, 6,083 patients initiated ibrutinib, among whom 2,771 (45.6%) patients had CLL (mean age of 74 years; 61% of men). At ibrutinib initiation, 46.6% of patients had a cardiovascular comorbidity. Most patients (91.7%) were not hospitalized during the exposure period for one of the cardiovascular or bleeding events studied. Hospitalizations were more frequent in patients with a cardiovascular comorbidity (5.9% versus 11.0%, p-value < 0.0001) and aged over 70 (5.9% versus 9.4%, p-value < 0.0001). The median TTNT was not reached. This is one of the largest cohorts of ibrutinib-treated patients in the world. The profile of CLL patients treated with ibrutinib was in accordance with the marketing authorization and reimbursement. This study confirmed effectiveness and safety data.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). Among 93 patients selected, median age at index was 67years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3months (IQR 8.7-25.4months), and median time from end of 1L therapy to 1LM initiation was 35.0days (IQR 25.0-53.9days). Median TTD was 9.3months (95% CI 6.1-11.3months). Median TTNT was 12.9months (95% CI 11.5-19.0months). This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.

Second-line (2L) treatment patterns and clinical outcomes among real-world (RW) patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with FOLFIRINOX (FFX) or gemcitabine + nab-paclitaxel (GnP) in the first-line (1L).

e16322 Background: FFX and GnP are the most common 1L treatments for pts with mPDAC. Approximately half of pts treated with these regimens continue to 2L, though optimal 2L treatment is unclear. We identified a RW sample of mPDAC pts treated with 1L FFX or GnP and assessed their 2L treatment patterns, duration of therapy (DoT), overall survival (OS), and time to next treatment (TTNT). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2021 who initiated 1L treatment with FFX or GnP ≤90 days from metastatic diagnosis date were included. To observe 2L treatment patterns, pts were required to have ≥1 year of follow-up unless death occurred first. Pts were censored at date of last activity absent death. Kaplan-Meier analyses were used to assess the median OS and TTNT from the start of 1L. Pts were grouped into five treatment categories: 1L FFX-only, 1L FFX + 2L GnP, 1L FFX + 2L other, 1L GnP-only, and 1L GnP + any 2L. Pts with 2L treatments were not restricted by whether they received 3L therapy or later. Results: 936 1L GnP and 712 1L FFX pts met the study inclusion criteria. 572 (61%) 1L GnP pts received 1L GnP-only and 364 (39%) received 1L GnP + any 2L (“any 2L” included 78 Nal-IRI, 59 FOLFOX, 57 FFX pts, and 170 pts with various combinations of chemotherapies and/or targeted therapies, with &lt; 50 pts per regimen). 300 (42%) 1L FFX pts received 1L FFX-only, 287 (40%) received 1L FFX + 2L GnP, and 125 (18%) received 1L FFX + 2L other (“2L other” included 35 capecitabine monotherapy pts, 27 G monotherapy pts, all other regimens &lt; 20 pts). Pts with 1L FFX were younger, slightly more likely to be male, and had slightly better ECOG scores than 1L GnP pts. Median 1L DoT was shorter for 1L-only pts compared to pts with 2L therapies. Median OS was shortest for 1L-only pts and longest for 1L FFX + 2L other. Median OS was similar for 1L FFX + 2L GnP and 1L GnP + any 2L. Median TTNT was similar across treatment categories with a 2L. Conclusions: In a RW sample of mPDAC pts, those with 1L-only had poor survival. Pts with 1L FFX + 2L GnP had a similar survival to 1L GnP + any 2L. [Table: see text]

Second-line (2L) treatment patterns and clinical outcomes among real-world (RW) patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with FOLFIRINOX (FFX) or gemcitabine + nab-paclitaxel (GnP) in the first-line (1L).

e16322 Background: FFX and GnP are the most common 1L treatments for pts with mPDAC. Approximately half of pts treated with these regimens continue to 2L, though optimal 2L treatment is unclear. We identified a RW sample of mPDAC pts treated with 1L FFX or GnP and assessed their 2L treatment patterns, duration of therapy (DoT), overall survival (OS), and time to next treatment (TTNT). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2021 who initiated 1L treatment with FFX or GnP ≤90 days from metastatic diagnosis date were included. To observe 2L treatment patterns, pts were required to have ≥1 year of follow-up unless death occurred first. Pts were censored at date of last activity absent death. Kaplan-Meier analyses were used to assess the median OS and TTNT from the start of 1L. Pts were grouped into five treatment categories: 1L FFX-only, 1L FFX + 2L GnP, 1L FFX + 2L other, 1L GnP-only, and 1L GnP + any 2L. Pts with 2L treatments were not restricted by whether they received 3L therapy or later. Results: 936 1L GnP and 712 1L FFX pts met the study inclusion criteria. 572 (61%) 1L GnP pts received 1L GnP-only and 364 (39%) received 1L GnP + any 2L (“any 2L” included 78 Nal-IRI, 59 FOLFOX, 57 FFX pts, and 170 pts with various combinations of chemotherapies and/or targeted therapies, with &lt; 50 pts per regimen). 300 (42%) 1L FFX pts received 1L FFX-only, 287 (40%) received 1L FFX + 2L GnP, and 125 (18%) received 1L FFX + 2L other (“2L other” included 35 capecitabine monotherapy pts, 27 G monotherapy pts, all other regimens &lt; 20 pts). Pts with 1L FFX were younger, slightly more likely to be male, and had slightly better ECOG scores than 1L GnP pts. Median 1L DoT was shorter for 1L-only pts compared to pts with 2L therapies. Median OS was shortest for 1L-only pts and longest for 1L FFX + 2L other. Median OS was similar for 1L FFX + 2L GnP and 1L GnP + any 2L. Median TTNT was similar across treatment categories with a 2L. Conclusions: In a RW sample of mPDAC pts, those with 1L-only had poor survival. Pts with 1L FFX + 2L GnP had a similar survival to 1L GnP + any 2L. [Table: see text]

Real-world evaluation of treatment pattern, time to next treatment (TTNT), healthcare resource utilization (HCRU), and cost of care in follicular lymphoma (FL).

e19044 Background: FL often becomes relapsed or refractory (R/R) to treatment. This study aimed to analyze TTNT, HCRU, and cost of care in FL. Methods: A retrospective study was conducted using Optum Clinformatics Data Mart to identify patients ≥18 years with ≥1 diagnosis for FL initiating 1L, 2L, 3L, or 4L treatment from 1/2019 to 02/2023. Patients were required to be continuously enrolled for 30 days pre- and post-index date, defined as the date of treatment initiation. Patients were categorized into mutually exclusive cohorts based on treatment regimen. TTNT was measured for patients who had a subsequent treatment within the study period. Total cost of care included both plan- and patient-paid claims, adjusted for inflation (2023 USD). HCRU included outpatient visits and inpatient admissions. Costs and HCRU were reported per patient per month over the treatment duration. Results: There were 4,525 patients initiating 1L treatment and 1,053, 304, and 97 patients initiating 2L, 3L, and 4L treatment, respectively. Median follow-up was 487 days (1L), 430 days (2L), 357 days (3L), and 276 days (4L). The mean age at the index was similar across cohorts (range: 69.6 [1L] to 71.9 [4L]). Rituximab monotherapy (R-mono) was the most utilized treatment in 1L and 2L, followed by bendamustine + rituximab (BR) and R-CHOP (Table). Lenalidomide + rituximab (R2) was the most utilized regimen in 3L and 4L. Obinutuzumab monotherapy (O-mono) use increased by line of therapy. The median TTNT across all regimens decreased by line of therapy (Table). BR and bendamustine + obinutuzumab (BO) had longer TTNT in 1L, while BR and R2 had longer TTNT in 3L. Inpatient admissions and outpatient visits increased with the line of therapy. Mean (SD) outpatient visits were 5.3 (3.2) in 1L, 5.8 (3.7) in 2L, 6.3 (4.0) in 3L, and 6.1 (3.3) in 4L, while inpatient admissions ranged from 0.1 (0.3) in 1L to 0.3 (0.4) in 4L. The mean total cost of care ranged from $40,538-$74,466, increasing by line of therapy. The mean total cost of care was consistently lowest in R-mono ($31,704-$36,197), while CAR-T had the highest total cost ($501,493-$522,378). R-mono had the lowest while R-CHOP had the highest mean outpatient visits across lines of therapy. Conclusions: Real-world TTNT decreased while costs and HCRU increased with each subsequent line of treatment, indicating a high disease burden in FL patients, particularly for those with R/R FL.These findings suggest the need for better treatment options for patients with FL, especially in 3L and 4L. [Table: see text]

Sézary Syndrome in West Sweden: Exploring Epidemiology, Clinical Features, and Treatment Patterns in a Registry-Based Retrospective Analysis.

Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.

Abstract PS08-09: Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE)

Abstract Background: trastuzumab deruxtecan (T-DXd) is a standard treatment for patients (pts) with HER2-positive (HER2+) and HER2-low metastatic breast cancer (MBC). HER2-low expression has been shown to be a highly unstable biomarker, and no data exists on the activity of T-DXd among pts with changes in HER2 status over time. Furthermore, limited data exists on the performance of regimens administered after progression on T-DXd. Methods: We analyzed data for pts with MBC receiving T-DXd at Dana-Farber Cancer Institute between 7/2017 - 2/2023 and at Duke Cancer Center between 3/2020 - 4/2022. The disease was categorized HER2+ if IHC 3+ or ISH-amplified at any time point; HER2-negative cases were categorized as HER2-low (IHC 2+/ISH- or IHC 1+) or HER2-0 (IHC 0) based on the last biopsy before T-DXd; the HER2 status for the primary tumor and at first metastatic diagnosis were also collected. We determined time to next treatment (TTNT), overall survival (OS), toxicities with T-DXd, TTNT based on dynamic HER2 status and TTNT with post-T-DXd regimens. Genomic data was available for 58 pts using an in-house NGS assay on archival tumor samples. Results: A total of 191 pts were included in the analysis (126 HER2+, 44 HER2-low, 21 HER2-0). Median age at metastatic diagnosis was 50.9 (range 21 - 78), 26% had de-novo MBC and 38% had history of brain metastases before T-DXd. The proportion of hormone receptor (HR)-positive tumors based on the last biopsy prior to T-DXd was 53% in HER2+, 68% in HER2-low and 57% in HER2-0; pts within each cohort had received a median of 2 prior lines of chemotherapy before T-DXd (range 0 - 9). With a median follow-up of 10.4 months, median TTNT was 10.4 months for HER2+, 7.6 months for HER2-low and 3.7 months for HER2-0 MBC (p &amp;lt; 0.001). Switch in HER2 status between primary tumor and pre-T-DXd biopsy significantly impacted outcomes, with the shortest TTNT observed in pts switching from HER2-low to HER2-0 (TTNT 3.0 months) compared with 5.6 months if switching from HER2-0 to HER2-low, and 9.4 months if having stable HER2-low status (p=0.006). Conversely, HER2 status switch within the metastatic setting did not impact outcomes (Table 1). No difference in TTNT was seen regardless of HR status (negative vs positive, 7.4 vs 10.2 months, p=0.25) or number of prior chemotherapies (≤2 vs &amp;gt;2, 10.1 vs 8.8 months, p=0.50). Median OS is shown in Table 1. At last follow-up, 55 pts remain on T-DXd (28.8%), 108 progressed (56.5%), 28 stopped due to toxicity (14.7%). A total of 22 pts (11.5%) developed interstitial lung disease (ILD, 6.2% grade [G]1, 3.1% G2, 1.6% G3, 0.5% G4, no G5). ILD occurred after a median of 8 months from T-DXd initiation and resolved in 63.6% of the cases, with a median time to resolution of 4 months (2 months for grade 1 events). 5 pts (2.6%) developed cardiotoxicity. T-DXd was dose reduced in 61 pts (31.9%), most often for fatigue (14.7%), nausea/vomiting (9.9%) or hematological toxicity (6.3%). Among 105 pts receiving post-T-DXd treatments, TTNT was 4 months for HER2+, 3.1 months for HER2-low and 4.3 months for HER2-0 MBC (p=0.62). Pts with HER2-negative tumors and ERBB2 hemizygous deletions (6/58, 10.3 %) had a TTNT with T-DXd of 4.1 months, vs 7.6 months without ERBB2 deletions (p=0.41). Additional biomarker data will be presented at the meeting. Conclusions: T-DXd showed promising real-world activity in pretreated pts with MBC, with the longest TTNT observed among pts with HER2+ disease or with stable HER2-low disease over time. Real world TTNT is relatively short post-T-DXd and further studies evaluating resistance mechanisms and optimal treatments in this setting are needed. Table 1 – TTNT and OS among patients with metastatic breast cancer receiving T-DXd and post-T-DXd regimens according to HER2 status The activity of T-DXd significantly differed according to the HER2 status of the disease, with the longest TTNT observed among patients with HER2+ disease (at any timepoint in time) and among patients with stable HER2-low disease over time. Regimens administered immediately after T-DXd achieved a similar performance irrespective of the HER2 status of the disease, with a TTNT ranging between 3.1 and 4.3 months. Citation Format: Paolo Tarantino, Melissa Hughes, Ross Kusmick, Laura Alder, Alyssa Pereslete, Laura Noteware, Heather Moore, Amanda Van Swearingen, Tianyu Li, Hersh Gupta, Kalie Smith, Stefania Morganti, Janet Files, Kerry Sendrick, Simone Buck, Deborah Dillon, Rinath Jeselsohn, Yvonne Li, Andrew Cherniack, Aleix Prat, Nay Nwe Nyein Chan, David Rimm, Giuseppe Curigliano, Sarah Sammons, Carey Anders, Nancy Lin, Sara Tolaney. Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE) [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 PS08-09.

Real-world data on diagnostics, treatment and outcomes of patients with hairy cell leukemia: The HCL-CLLEAR study.

Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9months (HCL) and 20.1months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAF V600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed.

Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer

Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC). To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan. This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022. Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose. Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR). A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months. In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.

Treatment Pattern, Healthcare Resource Utilization and Symptom Burden Among Patients with Triple Class Exposed Multiple Myeloma: A Population-Based Cohort Study

PurposeThis study aims to describe the treatment patterns, outcomes, health care utilization and symptom burden of triple class exposed (TCE) relapsed/refractory patents with multiple myeloma (MM) receiving a subsequent line of treatment (LOT). MethodsThis is a retrospective observational cohort study using administrative databases in Ontario, Canada. Outcomes were captured for TCE patients receiving a subsequent LOT and included: treatment regimen details, time to next treatment (TTNT), overall survival (OS), health care utilization, palliative care referral, and patient reported symptoms. ResultsOf the 16,777 patients diagnosed with MM between 2007-2021 in Ontario, 1358 (8%) patients were classified as TCE. Among the TCE MM patients, 489 (36%) received a subsequent LOT. The two most commonly administered therapies post TCE were carfilzomib/dexamethasone (n = 111, 22%) and pomalidomide/dexamethasone(n = 95, 19%). Median TTNT was 1.7 months (95%CI 1.2-2.4 months) and median OS 12.8 months (95%CI 10.8-16.5). Healthcare utilization was high with 276 (56%) of patients evaluated in an emergency department (ED) or admitted to hospital. There was high symptom burden as reported by patients with moderate-severe impairment in well-being, fatigue, pain and drowsiness noted in greater than 25% of the cohort. Palliative care referrals rates were low with only 10% (n = 48) patients referred to palliative care. Among the patients that died during study follow up, the majority died in hospital (n = 147,44%). ConclusionOur study reports one of the largest series of real-world TCE patients published and demonstrates the poor outcomes of TCE patients receiving a subsequent LOT.

Real-world (rw) treatment patterns, sequencing, and outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) receiving avelumab first-line maintenance (1LM) in the US.

605 Background: Avelumab 1LM is recommended in international guidelines for pts with la/mUC and disease control after 1L platinum-based chemotherapy (PBC). This study describes the treatment landscape after FDA approval of avelumab in June 2020 by examining pt characteristics, treatment patterns and sequencing, and rw outcomes in pts treated with avelumab 1LM. Methods: This noninterventional retrospective study identified pts with la/mUC who received avelumab 1LM in the US using data from Flatiron Health’s electronic health record database. Pts aged ≥18 y with ≥2 visits on/after Jan 1, 2011, diagnosed with la/mUC from Jan 1, 2019 - Dec 31, 2022, treated with 1L PBC followed by avelumab 1LM on/after Jul 1, 2020, ≤90 d after 1L PBC discontinuation, and with no disease progression ≤14 wk after 1L PBC were included. Treatment patterns in 1LM, second line (2L), and third line (3L) were assessed. Clinical outcomes, including rw progression-free survival (rwPFS), rw overall survival (rwOS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) from 1LM or 2L initiation, were assessed using Kaplan-Meier methods. Results: 214 avelumab 1LM-treated pts met eligibility criteria. Median age was 70 y; most pts were male (77%), White (66%), and had an ECOG of 0-1 (77%). Median follow-up from 1LM was 8.7 mo. Of 96 (45%) pts who received 2L treatment post avelumab 1LM, enfortumab vedotin (EV) monotherapy (55%) was most common, followed by carboplatin-based therapy (11%). Of 40 (42%) pts who received 3L treatment, EV monotherapy was most common (25%), followed by sacituzumab govitecan (20%). Median PFS and OS from start of avelumab 1LM was 5.1 (95% CI 4.1-7.0) and 23.8 (95% CI 18.2-NE) mo. Median TTNT from avelumab 1LM initiation was 7.0 (95% CI 5.6-8.6) mo. Of pts who received 2L EV, median rwPFS and rwOS from 2L initiation were 4.9 (95% CI 3.9-8.8) and 11.2 (95% CI 6.8-NE) mo. Further rw outcomes are presented in the Table. Conclusions: Clinical outcomes in this study are aligned with those of the JAVELIN Bladder 100 trial (NCT02603432), further supporting avelumab 1LM as a standard of care. With each additional line of therapy, substantial treatment attrition and less favorable clinical outcomes were observed. This study provides insights into the sequencing of treatments and management of pts with la/mUC after disease progression with avelumab 1LM in this rapidly evolving therapeutic landscape. The use of more effective upfront therapies may decrease the attrition rates. [Table: see text]

Assessment of circulating tumor DNA (ctDNA) burden and association with outcomes in metastatic gastric cancer (mGC) patients using real-world data (RWD).

276 Background: CtDNA burden has been shown to have potential uses in early cancer detection, guiding treatment decisions, residual disease and drug resistance detection, and treatment response monitoring. While published literature suggested that ctDNA may be prognostic of clinical outcomes for various tumor types, there is limited RWD assessing its use in mGC. This study uses RWD to evaluate the association of pre-treatment ctDNA burden with clinical outcomes in mGC. Methods: Patients were identified from the Guardant INFORM real-world clinical-genomic database, which links ctDNA results via plasma-based next-generation sequencing Guardant360 assay (G360) to de-identified claims data. Adult mGC patients in the US, who received NCCN guideline treatments post-diagnosis and underwent testing with G360 from June 2014 to March 2022 were included. For those who received first line (1L) therapy within 60 days after a G360 test result, median of the maximum variant allele fraction (mVAF) was used to classify them into high or low ctDNA burden groups, with undetectable ctDNA burden considered low. Associations with time to next treatment (TTNT) and overall survival (OS) were assessed using log rank tests and multivariable Cox proportion hazards models adjusting for age, sex, Elixhauser comorbidity score, and anatomical location. Results: 2,200 mGC patients were identified, of which 824 (37%) initiated 1L therapy within 60 days after a G360 test. Among the 824 patients, mean age was 63 years, 70% were male and 47% had gastric adenocarcinoma and 53% gastroesophageal junction cancer. Median mVAF among these patients was 2.9%, with 91% having detectable ctDNA. Patients with high ctDNA burden treated with 1L chemotherapy (Chemo) showed significantly worse TTNT and OS than low ctDNA burden patients (Median TTNT= 4.7 months vs 7.5 months, p&lt;0.001; Median OS=12.4 months vs 19.1 months, p&lt;0.001). Multivariable Cox analyses showed similar results for 1L Chemo group. Treatment group outcomes based on adjusted Cox models were reported (Table). Conclusions: We used RWD to demonstrate that high pre-treatment ctDNA burden was associated with worse clinical outcomes in a mGC population treated with 1L Chemo. Our analysis adds to the body of evidence that suggest ctDNA burden could be used as a prognostic biomarker for mGC. The small sample size of the other 1L treatment groups warrants further investigation because the use of IO-based therapy is expected to increase with recent approvals. [Table: see text]

Real-world treatment patterns and outcomes in patients with mCRC by MMR/MSI status.

52 Background: There are limited data on real-world (RW) treatment patterns and outcomes in patients (pts) with metastatic colorectal cancer (mCRC), especially those with deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) disease, as they progress through lines of therapy. Methods: Data were extracted from the Flatiron Health electronic health record-derived database. Pts aged ≥18 years diagnosed with mCRC and with ≥2 clinical visits between January 01, 2013 and October 31, 2022 were included. Treatment patterns by therapeutic category and specific agent/regimens were explored across 3 time periods anchored to the start date of first line (1L): years &lt;2017, 2017–2019 and ≥2020 for pts both with dMMR/MSI-H and proficient mismatch repair (pMMR)/microsatellite stability (MSS) disease. Analyzed outcomes, by treatment category, included overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT). Descriptive statistics and Kaplan–Meier analyses were conducted. Results: A total of 34,853 pts with mCRC were identified; 24,622 pts (70.6%) were tested for MMR or MSI status, of whom 1,594 (6.5%) were dMMR or MSI-H. After applying key eligibility criteria, 938 dMMR/MSI-H and 12,305 pMMR/MSS pts were included. Overall, chemotherapy-based treatment was the most common treatment category given to pts, but the use of immuno-oncology (IO) agents increased over time. In the dMRR/MSI-H cohort, IO was the most commonly used treatment in 1L and 2L after 2020, driven largely by the use of pembrolizumab. The median OS (mOS) from start of 1L, irrespective of treatment type, was 30.30 months (95% confidence interval [CI]: 24.47, 34.41) in the dMMR/MSI-H cohort and 23.78 months (95% CI: 23.32, 24.34) in the pMMR/MSS cohort. For pts with dMMR/MSI-H, those receiving 1L IO had a mOS of 57.60 months (95% CI: 42.43, not reached [NR]). In pts who had IO after 1L-chemotherapy alone or chemotherapy + targeted treatment, mOS was 52.63 months (95% CI: 38.06, NR) and 59.61 months (95% CI: 34.41, NR), respectively. In pMMR/MSS pts, chemotherapy alone or chemotherapy + targeted treatment had the longest OS when received as 1L-therapy, at 23.88 months (95% CI: 22.89, 25.10) and 24.28 months (95% CI: 23.55, 25.10), respectively. The median TTD and TTNT from start date of 1L, irrespective of treatment type, were 4.90 months (95% CI: 4.28, 5.20) and 7.96 months (95% CI: 7.04, 8.78), respectively, in the dMRR/MSI-H cohort, and 5.79 months (95% CI: 5.72, 5.95) and 10.33 months (95% CI: 10.07, 10.59) in the pMMR/MSS cohort. Conclusions: These real-world data from over 10,000 pts with mCRC supplement findings from clinical trials and limited reported RW evidence. While IO demonstrates significant improvement for pts with dMMR/MSI-H, and mOS is similar regardless of whether IO is given in the 1L or later setting, there remains a high unmet need in pMMR/MSS for additional effective treatment options.

Clinical impact of KRAS mutations in metastatic pancreatic ductal adenocarcinoma (PDAC).

619 Background: Mutations in the KRAS oncogene occur in most PDAC and lead to the activation of the KRAS protein. Little is known about the differential impact of KRAS mutations on the outcomes of patients receiving standard of care cytotoxic treatments for metastatic disease. KRAS inhibitors are emerging as promising options for this disease and understanding the impact of distinct KRAS mutations in patient outcomes is needed. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database from 5,369 patients. Adult patients with diagnosis of metastatic PDAC who received at least one line of systemic therapy and had sufficient data available were included in this analysis. Median time to next treatment (TTNT) and overall survival (OS) time were calculated for three common first-line treatments and KRAS mutations. TTNT and OS were calculated for each permutation of treatment and each KRAS mutation. Hazard ratios (HR) were generated for each KRAS mutation and treatment, accounting for potentially confounding variables. Results: Of the 5,369 patients, 2,472 met the inclusion/exclusion criteria. G12C had the shortest median OS (7.5 mo) and G12R had the longest (9.1 mo). Overall, KRAS mutation-positive patients had a median OS of 8.6 mo, compared to 11.7 mo for KRAS Wild Type (WT) patients. A Cox Proportional Hazard analysis of OS across KRAS mutation status found that G12C, G12V, G12D, and Other Non G12/13 KRAS had significantly higher HR than KRAS WT. A comparison of the three common first-line interventions for metastatic PDAC showed that FOLFIRINOX had the longest median TTNT (5.3 mo) and the longest OS (10.2 mo), while Gemcitabine had the shortest TTNT (2.6 mo) and OS (5.9 mo). A Cox Proportional Hazard analysis of OS across all patients found that Gemcitabine and Gemcitabine with Nabpaclitaxel had significantly higher HR than FOLFIRINOX. FOLFIRINOX had the longest TTNT in the G12C, G12V, G12D, G12R, and other non-G12/G13 KRAS groups (see table). Conclusions: Our data suggest that FOLFIRINOX has a longer TTNT than other first-line regimens for KRAS G12C, G12V, G12D, and G12R. KRAS G12C was associated with the shortest OS among common KRAS mutations.[Table: see text]

INSURE: a pooled analysis of ixazomib-lenalidomide-dexamethasone for relapsed/refractory myeloma in routine practice.

Aim: We pooled data from three observational studies (INSIGHT MM, UVEA-IXAand REMIX) to investigate the real-world effectiveness of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory myeloma. Materials & methods: INSIGHT MM was a prospective study conducted in countries across Europe, Asiaand North/Latin America while UVEA-IXA and REMIX were multicenter, retrospective/prospective studies conducted in Europe. Patients who had received IRd as ≥2nd line of therapy were analyzed. Primary outcomes were time-to-next treatment (TTNT) and progression-free survival (PFS). Results: Overall, 564 patients were included (median follow-up: 18.5months). Median TTNT and PFS were 18.4 and 19.9months; both outcomes were numerically longer for earlier versus later lines. Median treatment duration was 14.0months. Overall response rate was 64.6%. No new safety concerns were noted. Conclusion: The effectiveness of IRd in routine practice appears similar to the efficacy observed in TOURMALINE-MM1. IRd benefit in earlier versus later lines was consistent with previous reports.

Real-World Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment Patterns Among Patients with Chronic or Small Lymphocytic Leukemia (CLL/SLL) in US Community Oncology Practices

Background: BTKis have become the standard-of-care therapies for both frontline (1L) and relapsed/refractory (2L) CLL/SLL, and recently the NCCN listed both second-generation BTKis, zanubrutinib and acalabrutinib, as preferred agents over the first-generation BTKi ibrutinib based on toxicity profile. The objective of this study was to assess real-world clinical characteristics, treatment patterns, and adverse events (AEs) among BTKi-treated patients with CLL/SLL. Methods: This was a retrospective observational study of adult patients with CLL/SLL who initiated treatment between 01-Jan-2020 and 28-Feb-2023 in the community oncology setting across the US and were followed up through 31-May-2023. Included patients had to have at least 5 CLL/SLL visits or more CLL/SLL visits than non-CLL/SLL visits; all patients had to have 2 or more evaluation and management visits. The study included structured electronic health data from the Integra Connect-PrecisionQ de-identified real-world database. Descriptive analyses were conducted including all patients who received a BTKi, and a Kaplan-Meier analysis was performed for time-to-event outcomes. Results: A total of 2650 patients who received a BTKi were included in the study (2465: BTKi 1L; 185: BTKi naïve in 1L with use of BTKi in subsequent lines). The median (range) age of patients in the 1L BTKi and BTKi-later line groups was 71 (35-89) and 74 (42-89) years, respectively, and most included patients were male (Table). In 1L, 53.3% (n=1314/2465) were treated with ibrutinib, 43.3% (n=1068/2465) with acalabrutinib, and 3.4% (n=83/2465) with zanubrutinib. Among BTKi-later line patients, similar trends (45.9% [85/185] ibrutinib, 42.7% [79/185] acalabrutinib, 11.4% [21/185] zanubrutinib) were observed in 2L. The rates of cardiovascular AEs within the first 3 and 6 months of BTKi initiation were 10.1% (n=106/1048) and 13.4% (n=123/921) for patients treated with ibrutinib, 7.3% (n=56/767) and 9.8% (n=62/631) for acalabrutinib, and 7.3% (n=5/69) and 7.5% (n=3/40) for zanubrutinib, respectively. More than 10% of ibrutinib-treated patients discontinued therapy and switched to a second-generation BTKi. The median time to treatment discontinuation (95% CI) in the 1L setting was 12.7 (11.7, 15.3) months for ibrutinib, 15.7 (12.0, 20.4) months for acalabrutinib, and 12.9 (10.3, NR) months for zanubrutinib. The proportion of patients continuing treatment at 6 and 12 months was higher with zanubrutinib (72.3% and 61.4%, respectively) compared to acalabrutinib (62.6% and 53.1%) and ibrutinib (62.3% and 51.9%). The median time to next treatment (TTNT) (95% CI) was not reached (NR) (12.6 months, NR) for those who received zanubrutinib in the 1L, while it was 31.3 (26.5, 35.5) months for ibrutinib and 35.8 (31.8, NR) months for acalabrutinib. Conclusions: This study found that cardiovascular AEs at 6 months were higher among patients who received ibrutinib and acalabrutinib compared to zanubrutinib. While the study is limited by the smaller sample size and shorter follow-up period for the zanubrutinib group, the proportions of patients remaining on treatment were higher and the median TTNT was longer for patients who received zanubrutinib.

Characteristics and Outcomes of Patients Receiving Sequential Bruton's Tyrosine Kinase Inhibitor (BTKi)/B-Cell Lymphoma 2 Inhibitor (BCL2i) for Treatment of Chronic Lymphocytic Leukemia (CLL) in the Real-World (rw) Practice Setting

Introduction: Bruton's Tyrosine Kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitors (BCL2is) are targeted agents that have proven to be particularly effective in treating chronic lymphocytic leukemia (CLL). It is critical to understand the current utilization patterns and outcomes of patients receiving these therapies in a sequential manner in the real-world (rw). This study explored patient characteristics and treatment outcomes for patients who were exposed to and discontinued treatment with BTKis and BCL2is in two consecutive lines of therapy (LOTs) for CLL. Methods: Patients were identified in the COTA rw database, a Health Insurance Portability and Accountability Act-compliant database comprised of longitudinal data abstracted from the electronic health records of healthcare provider sites in the United States. Eligible patients met the following study criteria: Aged ≥ 18 years at diagnosis with a confirmed CLL/ small lymphocytic lymphoma (SLL) diagnosis who initiated second line (2L) therapy between January 1, 2014 - June 30, 2021 and discontinued two consecutive LOTs for the analysis in question. The treatment groups assessed were (1) patients who were exposed to and discontinued treatment with BTKi and BCL2i therapies in sequential LOTs, regardless of which agent(s) was initiated first (“BTKi/BCL2i treatment” group) and (2) patients who completed treatment in the same two LOTs, but who did not receive BTKi and BCL2i therapies in both LOTs (“other” group). Other non-BTKi/BCL2i therapies received included bendamustine+rituximab, rituximab monotherapy, investigational regimens, chlorambucil+obinutuzumab, and other regimens. Patients were considered to have discontinued a given LOT if the patient had a documented end date for the LOT for any reason, including treatment completion as indicated or premature discontinuation for any reason (i.e., toxicity, progression, etc.). Patients were ineligible if they had a documented diagnosis of a concurrent primary malignancy or histologic transformation at the time of CLL/SLL diagnosis or a history of other primary malignancies, excluding benign skin cancers, within 3 years prior to CLL/SLL diagnosis. The index date for the study was the initiation of the second LOT in the sequence. The observation period was defined as the duration of time from index date to the date of patient death or last visit date (if date of death was not available). Time to next treatment (TTNT) and rw progression-free survival (rwPFS) were evaluated using the Kaplan-Meier method. Rw overall response rate (rwORR) was the proportion of patients who had a clinician-documented PR or CR as the best response to a LOT. Results: A total of 67 patients were identified to have been exposed to and discontinued a BTKi/BCL2i treatment sequence (1L→2L: N=21, 2L→3L: N=23, 3L+: N=23). The median age at diagnosis was 63 years (IQR: 55, 70), and patients were predominantly White (76%), male (67%), and treated in the community setting (81%). 67.2% of patients who completed two consecutive BTKi/BCL2i therapies were diagnosed in 2014 or earlier. Median follow up time from diagnosis was 112.6 months (IQR: 72.4, 149.4). Outcomes analysis was conducted for patients who received a BTKi/BCL2i treatment sequence in 1L→2L relative to patients in the other treatment group in the same LOTs. Patients in the BTKi/BCL2i treatment group in 1L→2L (N=21) had more favorable rwPFS (41.8 months, HR 0.46, 95% CI: 0.23-0.93) relative to patients in the other treatment group in 1L→2L (N=833, 23.4 months). Median TTNT and rwORR for patients in the BTKi/BCL2i treatment group were not reached (NR) and 81.0%, respectively. Patients in the other treatment group experienced median TTNT of 21.4 months and rwORR of 78.3%. Conclusions: Our findings indicate that patients treated with BTKi/BCL2i sequences in 1L and 2L may have experienced improved outcomes relative to patients who received other sequences in the same LOTs. While research is beginning to investigate characteristics and outcomes for patients who received these therapies consecutively (Lew et al., Blood Adv 2021), future research should further examine these outcomes in a larger patient population and in patients who have already discontinued and relapsed on both BTKis and BCL2is.

Brentuximab Vedotin in the Treatment of Cutaneuous T Cell Lymphomas: A Multicenter, Retrospective, Case-Control Study from Italy

Brentuximab Vedotin (BV) is an anti-CD30 monoclonal antibody approved for relapsed/refractory CD30+ cutaneous T-cell lymphomas. The posology recommends its use until disease progression, unbearable toxicity, or completion of 16 cycles. A common side effect of BV is peripheral neuropathy (PN), which may lead to chronic complications and often leads to early treatment interruption. To reduce long-term side effects, clinicians often choose to interrupt BV early when the patient shows an adequate response. However, it remains uncertain whether this approach effectively reduces the incidence of PN. Furthermore, it is unknown whether this reduction in cumulative dose negatively impacts the relapse-free interval (RFI) or the time to next treatment (TTNT). This study aims to investigate whether a reduced BV treatment schedule is beneficial in terms of severe side effects compared to the standard schedule and to compare RFI and TTNT between the two schedules. The study was conducted retrospectively as a multicenter, observational case-control study. Clinical and pathological data from 71 patients (44 males, median age 66 yeas) were analyzed. Various CTCLs subtypes were represented in the study population (43 had MF, 7 had folliculotropic MF, 10 had pc ALCL, 3 had PTCL-NOS, and 8 had SS). The median follow-up duration was 525 days. Of the patients, 11 (15.4%) completed 16 cycles of BV, 21 (29.6%) stopped treatment due to disease progression (PD), 12(16.9%) experienced severe adverse events, 20 (28.1%) stopped treatment due to an adequate response based on the clinician's decision, the remaining patients were still under treatment at the time of data cut-off. Out of the 71 patients, 20 developed PN, with 6 of them experiencing severe (G3) symptoms. At the last follow-up, 7 (35%) cases of PN had resolved, 8 were mild (G1), and 5 remained moderate (G2). No differences were observed in PN incidence or the number of infusions between patients who achieved an adequate clinical response and those who developed PN. No significant differences were observed in the median number of BV infusions between the groups. Age at the time of the first infusion was the only variable associated with an increased risk of toxicity. However, no significant correlation was found between any variable and the incidence of PN. The median RFI for patients receiving all 16 cycles was 882 days (95% CI 461, NA), compared to 357 days (95%CI 313, NA) for those who stopped BV after an adequate response, but this difference was not statistically significant (Pv=0.25). Similarly, the median TTNT in patients receiving all 16 cycles was 814 days (lower 95% CI = 458, upper NA), compared to 502 days in patients who stopped BV after achieving an adequate response (324, NA; pV=0.6). In conclusion, based on the data analyzed, early interruption of BV after achieving an adequate response did not significantly reduce the incidence of severe adverse events or PN. Further data are required to determine if early interruption of BV negatively impacts patients' RFI or TTNT.

Efficacy and Safety of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Treatment-Naive, Higher-Risk Myelodysplastic Syndromes

Introduction: Azacitidine (Aza) has been shown to prolong survival in patients with treatment-naive, higher-risk myelodysplastic syndrome (HR MDS) compared to lower-intensity, conventional treatment regimens; however, improvement in clinical outcomes are needed. Clinical data on the synergy of Aza with venetoclax (Ven)-a selective, potent BCL-2 inhibitor-in the treatment of myeloid malignancies and the unmet need in HR MDS provide a rationale to evaluate Ven in combination with Aza in treatment-naive HR MDS. Here, we report efficacy and safety data in patients with treatment-naive HR MDS treated with Ven+Aza at the recommended Phase 2 dose (RP2D) in the safety expansion part of the Phase 1b study (NCT02942290). Methods: Adult patients were enrolled with de novo treatment-naive HR MDS defined by the Revised International Prognostic Scoring System (IPSS-R) score of &amp;gt;3 with an Eastern Cooperative Oncology Group performance status of ≤2, and bone marrow (BM) blasts &amp;lt;20% at baseline. Patients received Ven 400 mg orally daily on Days 1-14 and Aza 75 mg/m 2 intravenously or subcutaneously on Days 1-7 or on Days 1-5, 8, and 9 of each 28-day cycle (RP2D). The primary objective was to assess the complete remission (CR) rate. Key secondary objectives included determining marrow CR (mCR), overall response rate (ORR), hematologic improvement (HI), postbaseline red blood cell (RBC) and platelet transfusion independence (TI), overall survival (OS), duration of CR, time to next treatment (TTNT), transformation to acute myeloid leukemia (AML), and time to AML transformation. Responses were assessed by International Working Group 2006 criteria. Prophylactic antibiotics were mandated in Cycle 1 and recommended for Grade ≥3 neutropenia thereafter. Safety was analyzed in patients who received ≥1 dose of study treatment. Results: At thedata cutoff of May 31, 2023, 107 patients had received Ven+Aza at the RP2D. Key baseline characteristics for all treated patients are shown in Table 1A. Median age was 68 years (range, 26-87), 64% of patients had intermediate or poor cytogenetic risk, and &amp;gt;89% had ≥5% BM blasts. Median number of treatment cycles before transplantation was 3.0 (range, 1.0-11.0). At the median follow-up of 31.9 months (95% CI, 30.4-42.5), CR rate was 29.9% (95% CI, 21.4-39.5), with a median CR duration of 16.6 months (95% CI, 10.0-not reached [NR], Table 1B). Median OS was 26 months (95% CI, 18.1-51.5), with an estimated 12-month OS of 71.2% (95% CI, 61.4-78.9)and 24-month OS of 51.3% (95% CI, 41.2-60.5). Median OS for CR was NR. Median TTNT including transplantation was 6.8 months (95% CI, 5.6-8.3). Sixty-two (57.9%) patients received subsequent treatment, including transplantation in 42 (39.3%) patients; the median time to transplantation was 4.8 months (range, 1.4-16.8). Among patients who received transplantation post-study, 17 were transplant ineligible at study entry. Postbaseline TI rate was 61.7% for RBC and 72.0% for platelets. Median maximal duration of TI achieved was 5.4 months (range, 1.8-50.8) and 5.4 months (range, 1.9-56.0) for RBC and platelets, respectively. Postbaseline overall hematologic improvement (HI) was achieved in 51 (49.0%) of 104 evaluable patients, and specific responses included erythroid (40/93; 43.0%), platelet (32/74; 43.2%) and neutrophil (10/57; 17.5%) indices. All patients experienced ≥1 treatment-emergent adverse event (TEAE), with 94.4% of patients reporting grade ≥3 TEAEs. Serious adverse events (SAEs) occurred in 68.2% of patients. Common TEAEs of any grade were constipation (53.3%), nausea (49.5%), neutropenia (48.6%), thrombocytopenia (44.9%), febrile neutropenia (42.1%), diarrhea (41.1%), anemia (39.3%), vomiting (36.4%), and hypokalemia (26.2%). Grade ≥3 TEAEs reported in ≥20% of patients were neutropenia (48.6%), thrombocytopenia (43.0%), febrile neutropenia (42.1%), and anemia (34.6%). Infections were reported in 57% of patients, including SAEs in 40.2% of patients. Of the 59 deaths (55.1%) reported, 23 (21.5%) were due to disease progression and 7 (6.5%) to adverse events. Within 60 days after study start, 7 deaths (6.5%) were reported. Conclusion: Ven 400 mg for 14 days plus Aza combination was well tolerated with favorable responses of CR+PR+mCR in &amp;gt;80% and HI in nearly 50% of patients with treatment-naïve HR MDS. A separate Phase 3 study of this combination is ongoing to confirm survival benefit.

Health Care Resource Utilization and Total Costs of Care for Adult Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia in the United States: A Retrospective Claims Analysis

PurposeAlthough immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. MethodsWe selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period. Outcome measures included claim-based time to next treatment (TTNT), all-cause and adverse event (AE)–related HRU, and all-cause and AE-related costs. FindingsThe R/R B-ALL cohort (N = 203) was 60% male, median age of 41 years, and median Charlson Comorbidity Index score of 3.0. Mean (SD) follow-up was 17.8 (11.8) months. Of those who received 2L, 55.7% (113/203) required 3L, and 15% (30/203) initiated 4L+. Patients relapsed quickly, with a median TTNT of 170 days, 169 days, and 205 days for 2L, 3L, and 4L+, respectively. Hospitalization rates were high across each LoT (2L, 88%; 3L, 73%; 4L+, 73%), and the mean (SD) inpatient length of stay increased by LoT as follows: 8.6 (6.8) days for 2L, 10.6 (13.3) for 3L, and 11.6 (13.6) for 4L+. Mean (SD) overall costs were substantial within each LoT at $513,279 ($599,209), $340,419 ($333,555), and $390,327 ($332,068) for 2L, 3L, and 4L+, respectively. The mean (SD) overall/per-patient-per-month AE-related costs were $358,676 ($497,998) for 2L, $202,621 ($272,788) for 3L, and $210,539 ($267,814) for 4L+. Among those receiving blinatumomab or inotuzumab within each LoT, the mean (SD) total costs were $566,373 ($621,179), $498,070 ($376,260), and $512,908 ($159,525) for 2L, 3L, and 4L+, respectively. ImplicationsThese findings suggest that adult patients with R/R B-ALL relapse frequently with standard of care and incur a substantial HRU and cost burden with each LoT. Those treated with blinatumomab or inotuzumab incurred higher total costs within each LoT compared with the overall R/R B-ALL cohort. Alternative therapies with longer duration of remission are urgently needed, and HRU should be considered for future studies examining the optimal sequencing of therapy.