Time To Next Treatment Research Articles

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes

PurposeIntraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time.MethodsPatients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups.ResultsOf 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 − 94) days for IORT patients versus 52 (11 − 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001).ConclusionIORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

Real-world study of patients with locally advanced HNSCC in the community oncology setting.

There is a need to understand the current treatment landscape for LA HNSCC in the real-world setting. This retrospective study assessed real-world outcomes and treatment patterns of 1,158 adult patients diagnosed with locally advanced (stage III-IVB) HNSCC initiating chemoradiotherapy (CRT) within the period January 2015 to December 2017 in a large network of US community oncology practices. Structured data were abstracted from electronic health records. Demographic, clinical and treatment characteristics were analyzed descriptively overall and stratified by index treatment (cisplatin + radiotherapy [RT], cisplatin + other chemotherapy + RT, or cetuximab + RT). Time to next treatment (TTNT) and overall survival (OS) were measured using the Kaplan-Meier method, and median duration of treatment was assessed. OS was compared across treatment cohorts using multinomial logistic regression with inverse probability treatment weighting. To identify covariates associated with OS, a multivariable adjusted Cox proportional hazard model was used. This study examined 22,782 records, of which 2124 had stage III to stage IVB and no other cancers, and 1158 met all eligibility criteria. Among the treatment cohorts analyzed (cisplatin + RT, cisplatin + other chemotherapy + RT, or cetuximab + RT), cisplatin + RT was the most common concurrent chemotherapy (65.8%). Among 1158 patients, 838 (72.4%) did not initiate subsequent treatment and 139 (12.0%) died. The median TTNT and median OS were only reached by the cetuximab + RT cohort. Among patients with oropharynx primary tumor location, patients with human papilloma virus (HPV) positive status had the longest time on treatment and highest survival at 60 months. Covariates associated with improved survival were never/former tobacco use, HPV positive status, and overweight or obese body mass index. Covariates associated with poorer survival were age of 60+ years, primary tumor location of hypopharynx or oral cavity and Eastern Cooperative Oncology Group performance status score of 2+. These data describe real-world treatment patterns in locally advanced head and neck squamous cell cancer and sets the baseline to assess outcomes for future studies on the community oncology population.

Pretreatment CT Texture Parameters as Predictive Biomarkers of Progression-Free Survival in Follicular Lymphoma Treated with Immunochemotherapy and Rituximab Maintenance.

The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above -0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.

Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice

BackgroundNew drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2.MethodsA population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to adverse events (AEs). The Kaplan–Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used.ResultsThere were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7–35.2) and median duration of treatment was 17.5 months (IQR: 7.8–29.1). Median PFS was 19.5 months (95%CI 14.2–24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2–75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5–50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4–28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4–36.0). TPF was 19.8 months (95%CI 14.2–24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0–29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%).ConclusionsData suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Health resource utilization and costs of care for adult patients with relapsed or refractory mantle cell lymphoma in the United States: a retrospective claims analysis

ABSTRACT Objectives We assessed real-world healthcare resource utilization (HRU) and costs among US patients with relapsed or refractory mantle cell lymphoma (R/R MCL) by line of therapy (LoT). Methods We selected patients from MarketScan® (1/1/2016–12/31/2020): ≥1 claims of MCL-indicated first line (1L) therapies, ≥1 diagnoses of MCL pre-index date (1L initiation date), ≥6-month continuous enrollment pre-index date, second line (2L) therapy initiation, ≥18 years old at 2L, and no clinical trial enrollment. Outcomes included time to next treatment (TTNT), all-cause HRU, and costs. Results The cohort (N = 142) was 77.5% male, aged 62 years (median). Sixty-six percent and 23% advanced to 3L and 4L+, respectively. Mean (median) TTNT was 9.7 (5.9), 9.3 (5.0), and 6.3 (4.2) months for 2L, 3L, and 4L+, respectively. Mean (median) per patient per month (PPPM) costs were $29,999 ($21,313), $29,352 ($20,033), and $30,633 ($23,662) for 2L, 3L, and 4L+, respectively. Among those who received Bruton tyrosine kinase inhibitors, mean (median) PPPM costs were $24,702 ($17,203), $31,801 ($20,363), and $36,710 ($25,899) for 2L, 3L, and 4L+, respectively. Conclusions During the period ending in 2020, patients relapsed frequently, incurring high HRU and costs across LoTs. More effective treatments with long-lasting remissions in R/R MCL may reduce healthcare burden.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: One-year fixed-duration venetoclax-obinutuzumab (Ven-Obi) is a standard-of-care for patients (pts) with previously untreated chronic lymphocytic leukemia (CLL). Due to its ongoing follow-up, the CLL14 study provides unique insights into long-term outcomes of pts after Ven-Obi therapy. Methods: Pts with previously untreated CLL and coexisting conditions were randomized 1:1 to Ven-Obi or chlorambucil-obinutuzumab (Clb-Obi). Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included safety, rates of minimal residual disease (MRD), time to next treatment (TTNT) and overall survival (OS). Results: Of 432 enrolled pts, 216 were randomly assigned to Ven-Obi, 216 to Clb-Obi. At a median follow-up of 76.4 months (interquartile range 52.5–80.5), PFS remained superior for Ven-Obi compared to Clb-Obi (median 76.2 vs. 36.4 months; HR 0.40 [95% CI 0.31–0.52], p < 0.0001). Progressive disease (PD) occurred in 67 cases in the Ven-Obi arm with 39 second-line treatments, and in 141 cases in the Clb-Obi arm (with 103 second-line treatments). TTNT was significantly longer after Ven-Obi (6-year TTNT 65.2% vs. 37.1%; HR 0.44, 95% CI 0.33–0.58, p < 0.0001). In both arms, the most frequent second-line treatments were BTK inhibitors (61.5% in the Ven-Obi arm, 55.4% in the Clb-Obi arm). The PFS and TTNT difference between the two arms was maintained across all risk groups, including pts with TP53 mutation/deletion (median PFS 51.9 vs. 20.8 months; median TTNT 57.3 vs. 29.0 months) and unmutated IGHV status (median PFS 64.8 vs. 26.9 months; median TTNT 85.4 vs. 40.6 months). Multivariate analysis identified TP53 deletion/mutation, unmutated IGHV and lymph node size ≥5 cm as independent negative prognostic factors for PFS in pts treated with Ven-Obi. Five years after treatment completion, 17 (7.9% of the intention-to-treat population) pts in the Ven-Obi arm still had uMRD (<10−4 by NGS in peripheral blood), 22 (10.2%) had low (L)-MRD (≥10-4 and <10-2) and 23 (10.6%) high (H)-MRD (≥10-2), compared to 4 (1.9%) uMRD, 9 (4.2%) L-MRD and 18 (8.3%) H-MRD in the Clb-Obi arm. Overall, 48 deaths were reported in the Ven-Obi arm (9 PD related) and 70 in the Clb-Obi arm (26 PD related); 6-year-OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR 0.69 [0.48–1.01], p = 0.052). Second primary malignancies were reported in 30 pts in the Ven-Obi and 18 in the Clb-Obi arm; cumulative incidences 6 years after randomization were 14.2% and 8.5%, respectively (p = 0.071). No new safety signals were observed. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Roche, AbbVie Keywords: chronic lymphocytic leukemia (CLL), combination therapies Conflicts of interests pertinent to the abstract O. Al-Sawaf Consultant or advisory role: AbbVie, Ascentage, AstraZeneca, BeiGene, Eli Lilly, Gilead, Janssen, Roche Honoraria: AbbVie, Adaptive, AstraZeneca, BeiGene, Eli Lilly, Gilead, Janssen, Roche Research funding: AbbVie, BeiGene, Janssen, Roche Educational grants: AbbVie, AstraZeneca, Janssen, Gilead, Roche

Evaluation of immunotherapy response score (IRS) for predicting pembrolizumab (pembro) clinical benefit in patients (pts) with advanced solid tumors.

e14646 Background: IRS is a multivariable biomarker algorithm combining tissue-based tumor mutation burden (TMB) with quantitative gene expression biomarkers, previously validated to predict anti-PD-1 and anti-PD-L1 monotherapy (mono) benefit in an observational clinical trial (PMID: 36750617). Herein, we evaluated IRS in pts with advanced solid tumors across the Kaiser Permanente Northern California (KPNC) health system following a pre-specified statistical analysis plan. Methods: KPNC pts with valid IRS results (from 2018 – 2022; specimen collection years 2011-2021) and electronic health record (EHR) documented &gt; 1st line systemic pembro mono treatment were included; pts with gliomas or previous immunotherapy were excluded. All oncologic treatments were obtained from the EHR and standardized to determine time to next treatment (TTNT) as a real-world progression free survival endpoint. A within-pt evaluation was performed, comparing pembro TTNT to the pt’s immediate prior therapy line (prior) TTNT. The primary objective was to determine if IRS status (-H vs. Low [-L]) predicts pembro clinical benefit in Cox proportional hazards models through testing for interaction between IRS status and pembro/prior therapy TTNT. Results: With a data cutoff of 06/15/2022, 211 KPNC pts (142 2nd line and 69 &gt; 2nd line pembro) were eligible and included (from 24 solid tumor types). The median (m) pembro follow-up was 16.0 months. IRS-H pts (n = 77, 36%) had significantly longer pembro vs. prior TTNT (mTTNT 20.3 mo vs. 4.5 mo, log-rank p-value &lt; 0.0001), whereas IRS-L pts (n = 134, 64%) did not (mTTNT 3.3 mo vs. 5.2 mo, log-rank p-value 0.75); the interaction between IRS status and pembro/prior treatment was significant (interaction test p-value &lt; 0.0001). Conclusions: IRS predicted pan-solid tumor pembro mono benefit compared to prior therapy and may be a potential marker for pembro mono treatment decisions. Clinical trial information: NCT03061305 .

Real-world (RW) outcomes of patients (pts) with advanced breast cancer (aBC) with and without resistance alterations (alts) detected in cell-free circulating tumor DNA (ctDNA) prior to CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) treatment.

1081 Background: CDK4/6i plus ET is standard of care first-line (1L) therapy for hormone receptor positive (HR+), HER2- aBC. While molecular analyses from trials and pts have identified several mechanisms of resistance to CDK4/6i plus ET, currently, no biomarkers (outside of hormone status) are used for therapy selection. We utilized RW data to assess impact of putative baseline CDK4/6i+ET resistance alts (CDK4/6i+ET-R) on clinical outcomes among pts with aBC treated with CDK4/6i. Methods: Pts with aBC were identified via the Guardant INFORM database; those with a ctDNA test within 90 days prior to CDK4/6i start were included in this analysis. Based on previous studies, oncogenic or likely oncogenic alterations (as characterized by OncoKB) in the following genes were considered CDK4/6i+ET-R alts: RB1, PTEN, AKT1, CCNE1, ERBB2, FGFR1, FGFR2, and KRAS. Pts with &gt;1 CDK4/6i+ET-R alt were compared to pts without any CDK4/6i-R alts. Kaplan-Meier plots, log-rank tests (LR) and multivariate Cox proportional hazards models (HR) adjusted (adj) for age, sex, year of ctDNA test and line of therapy were used to assess differences in time to next treatment (TTNT) and overall survival (OS). Results: 1075 pts with aBC treated with CDK4/6i (27% receiving 1L treatment) met inclusion criteria, 293 of whom (27%) had &gt;1 alt in a CDK4/6i+ET-R gene. Pts with CDK4/6+ETi-R alts had significantly shorter TTNT (8.7 mos vs 14.2 mos, LR p=0.001; adj HR 1.36, 95%CI 1.11-1.66, adj p=0.003) and OS (28.3 mos vs 60.9 mos, LR p=&lt;0.0001; adj HR 2.19, 95%CI 1.69-2.82, adj p=&lt;0.0001) compared to those without. This divergence was more pronounced for patients receiving 1L CDK4/6i (TTNT: 10.7 mos vs 24.6 mos, LR p=0.006, adj HR 1.84, 95%CI 1.18-2.87, adj p=0.007; OS: 23.8 mos vs 67.3 mos, LR p&lt;0.0001, adj HR 3.27, 95%CI 1.89-5.62, adj p&lt;0.0001). Individual gene contributions towards less favorable TTNT are shown. Conclusions: We demonstrate via RW data that patients with &gt;1 pre-treatment ctDNA alt in a curated list of CDK4/6i+ET-R genes have significantly worse outcomes on CDK4/6i plus ET treatment, a difference more pronounced among patients receiving 1L therapy. This data is among the first successful efforts to validate a clinically useful multi-gene clinical biomarker that has the potential to predict CDK4/6i plus ET resistance. Further exploration of this signature’s prognostic and predictive utility for CDK4/6i plus ET use is ongoing to better refine personalized treatment selection in HR+/HER2- aBC. [Table: see text]

A real-world study of US patients with metastatic ovarian, fallopian tube, and peritoneal cancer (mOFPC) using integrated electronic health records (EHR) and claims datasets.

e17548 Background: Ovarian cancer is the most lethal gynecologic cancer. Detailed epidemiologic descriptions from a real-world database of a large population of ovarian and related cancer patients can provide insights into the characteristics, treatment patterns, and outcomes of these patients, and could serve as a useful benchmark while developing new therapies. Methods: This retrospective analysis uses the ConcertAI RWD360 dataset which is a real-world de-identified dataset of more than 6 million patients from across the United States derived from various EHR systems and integrated with a large administrative open claims dataset (&gt;90% overlap). 60429 patients in this dataset had OFPC out which 12406 patients had metastatic cancer. We present here the key characteristics of this mOFPC cohort including histology, biomarkers and top treatment patterns. We also performed overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT) analyses starting from initiation of 1st line of therapy (LoT) for all patients who received systemic treatment after metastatic diagnosis (8308 patients). Results: The top 5 histologies and biomarkers tested in this mOFPC cohort are presented in Table. The median OS from start of 1st LoT for this cohort was 2.45 years. The median TTD and TTNT across all 1st line therapies were 2.5 months and 5.5 months respectively. Top 2 treatments given as 1st LoT after metastatic diagnosis are also presented in Table. Chemotherapy (cis/carboplatin + pacli/docetaxel) and chemotherapy + bevacizumab were the most common 1st LoTs and there was no difference in the OS of patients treated with these two LoTs. Conclusions: This study describes the characteristics of a large US real-world cohort of mOFPC patients. Here we have presented data on the overall cohort, but further analysis of outcomes stratified by treatment arms, biomarkers and histology can be performed to better inform best treatments for specific sub-cohorts. [Table: see text]

Canadian (CAN) real-world outcomes for relapsed/recurrent (R/R) metastatic triple-negative breast cancer (mTNBC) in the first-line or later (1L+) setting by early or late recurrence status.

e18798 Background: Little epidemiological data characterizing the mTNBC population in Canada exist, limiting the understanding of treatment patterns, attrition rates, and unmet need for CAN patients (pts) with R/R mTNBC. This study examined real-world outcomes and palliative treatment patterns for CAN pts with 1L+ R/R mTNBC, stratified by early vs late recurrence. Methods: This retrospective study used real-world, population-based data from the Oncology Outcomes database in Alberta to identify pts diagnosed with early stage (I to III) TNBC between 2010-2019 who progressed to mTNBC. Algorithms reliably identified recurrent pts as those who received 2+ cycles of systemic therapy &gt; 240 days from the initiation of adjuvant treatment or surgery. Clinical outcomes from 1L+ treatment of mTNBC, including time to next treatment (TTNT) or death and overall survival (OS), were ascertained. Diagnosis, demographics, treatment patterns, and attrition rates were stratified by treatment-free interval (TFI), early (8-12 mo TFI) or late ( &gt; 12 mo TFI). Results: Data from 181 CAN pts with R/R mTNBC (recurred early, n = 59; recurred late, n = 122) were analyzed. Baseline characteristics were generally comparable between groups. Pts who recurred late were on average older at recurrence (59 y vs 55 y, P= 0.03) and less likely to be stage III (21% vs 51%, P&lt; 0.001) at initial diagnosis. The median time to recurrence was 17 mo. The most common 1L therapies were capecitabine monotherapy (35%), other chemotherapy combinations (16%), and taxane monotherapy (12%), with a median duration of therapy (DOT) of 4.9 mo, 3.5 mo, and 4.5 mo, respectively. Rates of attrition between lines of therapy (LOT) were relatively high, with 96 pts (53%) initiating 2L therapy (among the 85 pts who did not start 2L treatment, 63 had died). Median DOT was 3.6 mo for 1L, 3.0 mo for 2L, and 3.0 mo for 3L. Stratifying by early or late recurrence did not show differences in TTNT (4 mo vs 4 mo; HR, 0.94; 95% CI, 0.64-1.38; P= 0.75) or OS (10 mo vs 11 mo; HR, 0.96; 95% CI, 0.64-1.44; P= 0.84). Exploratory analyses showed improved OS (23 mo vs 10 mo; HR, 0.60; 95% CI, 0.40-0.92; P= 0.02) in pts with TFI ≥24 mo (n = 61) but not in pts with TFI 12-24 mo (11 vs 10 mo; HR: 0.96; 95% CI: 0.64-1.44; P= 0.84) vs pts with TFI of 8-12 mo. Conclusions: This retrospective study showed higher than expected rates of early recurrence and high attrition between LOT in a CAN breast cancer population that progressed to mTNBC. The short DOT across lines was similar and consistent with CAN practice. OS for 1L+ R/R mTNBC were similar for individuals who recurred between 8-12 vs 12-24 mo. These findings confirmed the poor prognosis of pts with R/R mTNBC and the need for improved therapies especially in 1L, where the most common treatments, including capecitabine, may not deliver the most meaningful impact.

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: A retrospective observational cohort study.

e21524 Background: The association of objective imaging response with first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in a real-world context. We compared likelihood of objective response between patients receiving first line anti-programmed cell death protein 1 (anti-PD1) monotherapies (pembrolizumab or nivolumab), or combination nivolumab with the cytotoxic T-cell lymphocyte-antigen 4 inhibitor ipilimumab and outlined the association between objective response and baseline characteristics and survival outcomes. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from 2013-2020 in Alberta, Canada. Best imaging response was assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1. The primary outcome was likelihood of objective imaging response (complete or partial response) between patients receiving anti-PD1 monotherapy and those receiving combination nivolumab-ipilimumab. Secondary outcomes were the identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT) endpoints. Results: Of the 255 patients included, 49/255 (19.2%) had complete response 112/255 (43.9%) had partial response, 28/255 (11.0%) had stable disease, and 66/255 (25.9%) had progressive disease. Median OS was not evaluable (NE) (95% CI NE-NE) for complete responders, NE (95% CI 52.93 months-NE) for partial responders, 21.30 months (95% CI 15.20 months-NE) for stable disease, and 7.72 months (95% CI 5.77-10.6 months) for progressive disease (log rank p &lt; 0.0001). A robust delineation of TTNT by imaging response was also seen. Likelihood of objective response was similar between patients treated with nivolumab-ipilimumab compared to those receiving anti-PD1 monotherapy (OR 1.87 95% CI 0.85-4.20, p = 0.124). Normal LDH level (OR 2.13; 95% CI 1.01-4.35, p = 0.047), non-mucosal primary site (OR 9.09; 95% CI 2.44-33.33, p &lt; 0.001), and absence of BRAF V600E mutation (OR 3.23; 95% CI 1.39-7.69, p = 0.007) were independently associated with likelihood of objective imaging response in multivariable analysis. Conclusions: In this real-world analysis, we demonstrate no significant difference in likelihood of objective response between patients treated with anti-PD1 monotherapy and combination nivolumab-ipilimumab, and demonstrate that a normal LDH level, non-mucosal primary site, and absence of BRAF V600E mutation are associated with response. Imaging response was also strongly associated with both OS and TTNT irrespective of therapy received. These results may help inform treatment selection, and aid in counseling of advanced melanoma patients treated with first line ICI therapy in a routine clinical practice setting.

Real-world (RW) dosing patterns and outcomes among chronic lymphocytic leukemia (CLL) patients (pts) with or without an ibrutinib (IBR) dose adjustment (DA) in first-line (1L).

7537 Background: Pts treated for CLL with IBR, a once-daily Bruton’s tyrosine kinase inhibitor with dosing flexibility options, may adjust their daily dose to help prevent recurrence or worsening of adverse events, while preserving efficacy. This RW study describes outcomes for CLL pts treated with 1L IBR who did or did not have a DA. Methods: Electronic medical records from the Acentrus database (1/1/2016-4/30/2022) were used to identify CLL pts initiated on 1L IBR (index date). The first 6 months post-index were used to identify pts who remained on a starting dose of 420mg/day or with a DA (reducing to a dose lower than 420mg/day; reasons for DA not available). Treatment adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT) were described for patients with and without a DA. Descriptive analyses are reported for all pts and among a subgroup of pts with high cardiovascular (CV) risk, defined as having a pre-existing CV comorbidity or a high CV risk score (CV subgroup). Results: 1,171 CLL patients were initiated on 1L IBR at the recommended dose of 420mg/day (Table). Of those, 1,038 (88.6%) remained on 420 mg for ≥6 months (mean age=70.2 years, 33.6% female, median follow-up: 30.5 months); 229 (19.6%) had a DA at any time post-index (median time to DA: 5.5 months) and 126 had the DA during the first 6 months (mean age=72.2 years, 42.9% female, median follow-up: 35.1 months). Mean PDC and MPR were descriptively higher in pts with a DA (overall: PDC=0.81, MPR=0.84; CV subgroup: PDC=0.78, MPR=0.81) relative to pts with no DA (overall: PDC=0.70, MPR=0.73; CV subgroup: PDC=0.69, MPR=0.72). Median TTNT was not reached for pts with or without a DA; 12-month Kaplan-Meier (KM) rates were similar for pts with a DA (overall: 89.1%; CV subgroup: 92.7%) and with no DA (overall: 92.5%; CV subgroup: 92.0%). Conclusions: Among CLL pts initiating 1L with standard-of-care IBR, 19.6% had a DA. Those with a DA had descriptively higher treatment adherence with no detriment to TTNT, relative to those who maintained 420mg/day starting dose, regardless of baseline CV risk. These findings are consistent with other RW studies and suggest that IBR DA can be an effective treatment strategy that does not negatively affect efficacy while being well-tolerated outside of clinical trials. [Table: see text]

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Real-world treatment outcomes in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were treated with first-line single-agent ibrutinib vs. chemoimmunotherapy.

e19509 Background: Real-world evidence on Bruton Tyrosine Kinase Inhibitor treatment vs chemoimmunotherapy (CIT) for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) has been limited to certain practice settings; research using a large and more comprehensive data source is warranted. Methods: This retrospective cohort study evaluated treatment outcomes among patients with CLL/SLL treated with first-line (1L) ibrutinib (IBR) or CIT using the US claims data from the Komodo Health payer-complete dataset, derived from &gt;150 private insurers and &gt;140 million insured individuals from 2015 to 2022. This study included adult patients with CLL/SLL who initiated 1L single-agent IBR or CIT (defined as no prior CLL/SLL treatment for ≥12 months in the baseline period) on or after March 2016. Time to next treatment (TTNT) was defined as the time from initiation (index date) of 1L treatment to treatment add-on or switch to a next line of therapy ≥29 days post-index and was compared using Cox proportional hazards models. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Results: A total of 3570 1L IBR- and 2391 CIT-treated patients were included, with the mean age 68 vs 64 years, 63% vs 66% male, and mean Quan-Charlson Comorbidity Index score 2.87 vs 3.05, respectively. Median follow-up was 26 vs 31 months, and 13% vs 26% of patients recorded a next treatment during the study period for IBR and CIT, respectively. At 1-, 3-, and 5-year post-index, the probabilities (95% confidence interval [CI]) of not initiating a new treatment were 92% (91%-93%), 83% (81%-84%) and 76% (73%-78%) vs 88% (87%-89%), 70% (68%-73%) and 56% (53%-60%) for the IBR and CIT cohorts, respectively. After controlling for baseline characteristics, 1L IBR patients were significantly less likely to initiate the next line of therapy during the study period (hazard ratio 0.61, 95% CI 0.54-0.69, p&lt;0.001). Conclusions: 1L single-agent IBR was associated with a significantly lower risk of advancing to next line of treatment compared to CIT in this large claims-based data set, reinforcing real-world effectiveness of 1L IBR for CLL in an insured US patient population. [Table: see text]

Zanubrutinib plus obinutuzumab versus obinutuzumab in patients with relapsed/refractory follicular lymphoma: Updated analysis of the ROSEWOOD study.

7545 Background: In an early-phase study, the combination of zanubrutinib plus obinutuzumab (ZO) was well tolerated and associated with an early signal of efficacy in patients (pts) with follicular lymphoma (FL) (Tam et al. Blood Adv 2020). ROSEWOOD (NCT03332017) is a phase 2, randomized study designed to assess efficacy and safety of ZO vs obinutuzumab (O) in pts with relapsed/refractory (R/R) FL. Here, we present an updated analysis with a median follow-up of 20.2 mo. Methods: Pts with R/R FL (grade 1–3a) who received ≥2 lines of therapy including an anti-CD20 antibody and alkylating agent were randomized 2:1 to receive ZO or O. Zanubrutinib was given at 160 mg twice daily until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and safety. Results: A total of 217 pts were randomized (145 for ZO; 72 for O). Median age was 64 years. Of the 217 pts, 114 (52.5%) had a high Follicular Lymphoma International Prognostic Index (FLIPI) score at screening and 123 (56.7%) pts had high tumor burden criteria according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. Median number of prior lines of therapy was 3 (range, 2–11). A total of 114 (52.5%) pts were refractory to rituximab; 214 (98.6%) pts received prior immunochemotherapy. Prior exposure to anticancer drugs included anthracyclines (80.6%), cyclophosphamide (94.0%), and bendamustine (54.8%). ORR was 69.0% (ZO) vs 45.8% (O) ( P = 0.0012). Complete response rate was 39.3% (ZO) vs 19.4% (O); 18-mo DOR rate was 69.3% (ZO) vs 41.9% (O); median PFS was 28.0 mo (ZO) vs 10.4 mo (O) (hazard ratio [HR], 0.50 [95% CI: 0.33, 0.75]; P = 0.0007). Median TTNT was not evaluable for ZO and 12.2 mo for O (HR, 0.34 [95% CI: 0.22, 0.52]; P &lt; 0.0001). Estimated OS rate at 24 mo was 77.3% (ZO) and 71.4% (O), with median OS not reached in either arm. Nonhematologic treatment-emergent adverse events of any grade that occurred more frequently for ZO vs O ( &gt; 5% difference) were petechiae (6.3% vs 0%) and herpes zoster infection (6.3% vs 0%); in contrast, pyrexia (13.3% vs 19.7%) and infusion-related reaction (2.8% vs 9.9%) occurred more frequently in pts on O. When adjusted for duration of treatment exposure, incidences of infection and cytopenia were similar, and incidence of all grades of hemorrhage was 2.4 (ZO) vs 1.3 (O) persons per 100 person-months. Two pts in each treatment group reported major hemorrhage. Incidences of atrial fibrillation and hypertension were low and similar in both treatment arms. Conclusions: ZO demonstrated meaningful activity and a manageable safety profile in pts with heavily pretreated R/R FL, representing a potential novel therapy. Clinical trial information: NCT03332017 .

Real-world study of treatment patterns and clinical outcomes in patients with metastatic non-small cell lung cancer (mNSCLC) post-approval of immunotherapy in the community oncology setting.

6629 Background: Clinical outcomes in patients with mNSCLC have improved post-approval of immunotherapy (IO). However, limited real-world data exists describing the evolution of treatment patterns and impact on outcomes in later lines of therapy (LOT). Here we describe the treatment landscape and outcomes of patients with mNSCLC without driver mutations within community oncology settings. Methods: This retrospective observational study included adult patients with mNSCLC who initiated first LOT (LOT1) for mNSCLC in the US Oncology Network from 1/1/2015 to 12/31/2020 (followed through 3/31/2022), using structured electronic health records. Patients who initiated LOT1 with a targeted therapy or EGFR/ALK/ROS1 inhibitor during any LOT were excluded. Second, third, and fourth LOT (LOT2, LOT3, LOT4) were assigned using start and stop dates. Treatment patterns up to LOT4 were summarized descriptively by period of treatment initiation (early-IO period: 2015–2017; post-IO period: 2018–2020). Overall survival (OS) and time to next treatment (TTNT) were assessed by LOT using Kaplan-Meier analysis. Results: Overall, 11,035 patients met study criteria, of which 3,835 (35%) patients initiated LOT2, 1,264 (11%) patients initiated LOT3, and 393 (4%) patients initiated LOT4 between 2015 and 2020, respectively. From 2015–2017 to 2018–2020, pembrolizumab plus platinum chemotherapy with pemetrexed or paclitaxel as LOT1 increased from 3% (n = 176) to 42% (n = 2,448), and pembrolizumab monotherapy increased from 9% (n = 465) to 26% (n = 1,518). In patients who initiated LOT2, IO followed by docetaxel ± ramucirumab increased from 1% (n = 15) to 15% (n = 295), whereas this sequence from LOT2 to LOT3 was used in 23% (n = 111) from 2015–2017 and 20% (n = 159) from 2018–2020. Median (95% CI) OS was 13.3 (12.6, 14.0) months vs. 14.7 (13.8, 15.3) months from initiation of LOT1 in 2015–2017 vs. 2018–2020, respectively (P = 0.187). Clinical outcomes by LOT and period of treatment initiation are presented as median (95% CI) in the table below. Conclusions: Understanding evolving treatment patterns in the community oncology setting is important for uncovering opportunities for mNSCLC treatment optimization. This descriptive study reveals the increasing use of mono- and combination IO followed by docetaxel ± ramucirumab in the community setting. Additionally, longer OS was noted in the post-IO period, suggesting possible extended benefits from earlier LOT. [Table: see text]

Single‐agent rituximab as an effective salvage therapy in pre‐treated hairy cell leukemia

Introduction: Hairy cell leukemia (HCL) patients usually experience multiple disease relapses during the course of their disease. The CD20 antigen is highly expressed on the surface of hairy cells. Single-agent rituximab can be a suitable treatment options in patients relapsing after repeated courses of purine analogs, if purine analogs are contraindicated (e.g., in case of poor bone marrow cellularity, high disease infiltration predicting long-lasting aplasia), especially if newer agents (such as moxetumomab or vemurafenib) are not easily available (as it happens in several countries). Methods: Our institutional series of HCL patients receiving single-agent rituximab as salvage therapy was retrospectively reviewed. Patients received rituximab at the standard dose of 375 mg/m2 weekly for 4 weeks. The main study objectives were overall response rate (ORR), time-to-next treatment (TTNT), progression-free survival (PFS) and overall survival (OS). Responses have been categorized according to the Consensus Resolution Criteria. Results: Thirty-three patients received 39 courses of rituximab (4 patients received it twice, one patient three times), in median as third line of therapy (range 2–8). First rituximab was given at a median age of 61 years and at a median time from disease diagnosis of 65 months. Out of 39 courses, a complete response was obtained in 28.2% of cases, a partial response in 23.1% and a minimal response in 20.5%, yielding an ORR of 71.8%. In 28.2% of patients, we observed no response. Median TTNT was reached at 33 months (65% at 2 years), while median PFS was reached at 24 months (51% at 2 years). Median OS resulted of 154 months (22% at 20 years). Among the 5 patients receiving rituximab more than once, all responded after the first course, although the ORR after the second or later course was only 50%. Median TTNT following the first rituximab was 38.5 months in these patients, ranging from 15 to 205 months. Keywords: Immunotherapy, Lymphoid Cancers No conflicts of interests pertinent to the abstract.

Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database.

Evaluate the overall survival (OS) of patients with multiple myeloma (MM) at different treatment stages in France. This retrospective observational cohort study used data from the French National Health Insurance database to study patients with MM (diagnosis 2013-2019). Patient outcomes included OS (all-cause mortality), time-to-next treatment (TTNT), and duration of therapy (DoT) from initial diagnosis, the start of different lines of therapy (LOTs), triple-class exposure (TCE), and subsequent treatment following TCE. The Kaplan-Meier method analyzed "time-to-event" data. From diagnosis, death rates increased from 1% at 1 month to 24% at 2 years; median OS was 63.8 months (N = 14 309). Median OS from the start of LOTs declined from 61.0 months (LOT1) to 14.8 months (LOT4). Median OS from TCE start was 14.7 months. There was a large variation in TTNT within LOTs (e.g., LOT1: bortezomib + lenalidomide: TTNT = 26.4 months, OS = 61.7 months; lenalidomide: TTNT = 20.0 months, OS = 39.6 months); DoT was similar for LOT1 and LOT2, then progressively declined at LOT4. Patients with stem cell transplant, younger age, and less comorbidity had better survival outcomes. Patients with MM face a poor prognosis after relapse to multiple LOTs and TCE, demonstrating a worsening of survival outcomes. Access to novel therapies may improve outcomes.

Analysis of real-world data to investigate evolving treatment sequencing patterns in advanced non-small cell lung cancers and their impact on survival.

Although optimal sequencing of systemic therapy in cancer care is critical to achieving maximal clinical benefit, there is a lack of analysis of treatment sequencing in advanced non-small cell lung cancer (aNSCLC) in real-world settings. A retrospective cohort study of 13,340 lung cancer patients within the Mount Sinai Health System (MSHS) was performed. Systemic therapy data of aNSCLC in 2,106 patients was the starting point in our analysis to investigate how treatment sequencing has evolved, the impact of sequencing patterns on clinical outcomes, and the effectiveness of 2nd line chemotherapy after patients progressed on immune checkpoint inhibitor (ICI)-based therapy as the 1st line of therapy (LOT). There is a significant shift to more ICI-based therapy and multiple lines of targeted therapy after 2015. We compared clinical outcomes of two patient populations with different treatment sequencing patterns, with the 1st group receiving chemotherapy as the 1st LOT followed by ICI-based treatment, and the 2nd group treated in the opposite order receiving a 1st line ICI-containing regimen followed by a 2nd line chemotherapy. No statistically significant difference in overall survival (OS) was observed between the two groups [group 2 vs. group 1, adjusted hazard ratio (aHR) =1.36, P=0.39]. We assessed the efficacy of the 2nd line chemotherapy in three patient populations given either 1st line ICI single agent, 1st line ICI-chemotherapy combination, or 1st line chemotherapy alone, there was no statistically significant difference in time-to-next treatment (TTNT) and in OS among the three patient groups. Analysis of real-world data has shown two treatment sequencing patterns in aNSCLC, ICI followed by chemotherapy or chemotherapy followed by ICI, achieved similar clinical benefit. The chemotherapies routinely used following platinum doublet 1st LOT, is effective as the 2nd line option after ICI-chemotherapy combination in the 1st line setting.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.