Longer Time To Next Treatment Research Articles

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]

Real-World Treatment Patterns and Outcomes by Line of Therapy and Race in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated in the United States: Results From the Final Analysis of the Prospective, Observational, informCLL Registry

BackgroundinformCLL is the largest US-based prospective, observational registry of patients with chronic lymphocytic leukemia (CLL) initiating FDA-approved treatment in the era of targeted therapy. Patients and MethodsPatients were enrolled between October 2015 and June 2019. Data were collected for baseline characteristics, treatment patterns, outcomes, and safety. ResultsIn total, 1459 eligible patients were enrolled (first line, n = 854; relapsed/refractory, n = 605). The most common index treatments were ibrutinib (first line, 45%; relapsed/refractory, 49%) and chemoimmunotherapy (first line, 43%; relapsed/refractory, 20%). With median follow-up of 31.8 and 30.9 months in first-line and relapsed/refractory cohorts, respectively, median time to next treatment (TTNT) in patients who received any index treatment was not reached (NR) and 48.6 months; estimated proportions without next-line therapy at 48 months were 64% and 50%. Median overall survival (OS) was NR for both cohorts; estimated 48-month OS rates were 81% and 64% in first-line and relapsed/refractory cohorts, respectively. In match-adjusted analyses, TTNT was improved with first-line ibrutinib versus chemoimmunotherapy (median NR vs. 56.5 months; hazard ratio, 0.74; 95% CI, 0.56-0.98). Exposure-adjusted rates of AEs leading to discontinuation and serious AEs were lower with ibrutinib versus chemoimmunotherapy. Estimated 36-month OS rates were similar in Black versus White patients who received any index treatment (first line, 87% vs. 83%; relapsed/refractory, 74% vs. 74%) or ibrutinib (first line, 97% vs. 85%; relapsed/refractory, 81% vs. 77%). ConclusionIn this prospective, large, real-world CLL registry, first-line ibrutinib was associated with longer TTNT than chemoimmunotherapy, with sustained benefit up to 4 years of follow-up.

Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study

PurposeImmune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.MethodsWe analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).ResultsA total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046).ConclusionICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.

Prostate-specific antigen doubling time predicts the efficacy of site-directed therapy for oligoprogressive castration-resistant prostate cancer

BackgroundIn recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. MethodsWe reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). ResultsA PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). ConclusionPSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.

Real-World Outcomes Following First-Line Treatment in Patients with Advanced Ovarian Cancer with Multiple Risk Factors for Disease Progression who Received Maintenance Therapy or Active Surveillance.

We evaluated real-world outcomes in patients with advanced ovarian cancer (AOC) based on their cumulative risk profile and maintenance therapy (MT) status following first-line (1L) treatment. This retrospective observational study of a nationwide electronic health record-derived de-identified database included adult patients diagnosed with stageIII/IV OC from January1, 2011 to February28, 2021, who received 1L therapy and had ≥ 12weeks of follow-up after the index date (end of 1L therapy). Patients were grouped according to whether they received MT or active surveillance (AS) following 1L treatment and by the cumulative number of risk factors (RF) present (stageIV disease; no surgery/treated with neoadjuvant therapy and interval debulking surgery; had postoperative visible residual disease; and had BRCA wild-type disease/unknown BRCA status). Time to next treatment (TTNT) and overall survival (OS) were assessed with a cloning and inverse probability of censoring (IPC)-weighted Kaplan-Meier method. Among 1920 patients, 22.2% received MT and 77.8% received AS. Median IPC-weighted TTNT and OS were 13.3months (95%CI 11.7-15.8) and 39.1months (95%CI 32.5-48.6) in the MT cohort, respectively, and 8.6months (95%CI 8.0-9.5) and 38.4months (95%CI 36.4-41.0) in the AS cohort, respectively. Almost all patients had ≥ 1 RF (MT 95.3%; AS 96.7%). Median IPC-weighted TTNT was shorter among patients with more RF in both cohorts (MT: 1RF, 19.3months, 95%CI 13.5-37.8; 2RF, 17.2months, 95%CI 12.8-20.2; 3RF, 11.0months, 95%CI 8.2-13.8; 4RF, 7.0months, 95%CI 6.2-8.8; AS: 1RF, 17.7months, 95%CI 13.5-22.3; 2RF, 10.2months, 95%CI 9.1-11.5; 3RF, 6.5months, 95%CI 5.8-7.4; 4RF, 4.1months, 95%CI 3.5-4.5). Regardless of RF number, MT was associated with longer TTNT in real-world patients with AOC.

Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10−6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy in Patients With Metastatic Colorectal Cancer With Measures of Microsatellite Instability, Mismatch Repair, or Tumor Mutational Burden

The KEYNOTE-177 trial demonstrated that patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (DMMR) have better outcomes when receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy. Data on performance of ICIs in patients with MCRC in standard practice settings remain limited, and direct MMR vs MSI outcome association comparisons are lacking. To validate MSI (determined by next-generation sequencing [NGS]) as a biomarker of ICI effectiveness among patients with MCRC in standard practice settings and examine the association of MSI assessed by NGS, DMMR by immunohistochemistry, and tumor mutational burden (cutoff, 10 mutations/megabase) with ICI outcomes. This comparative effectiveness research study of outcomes in prospectively defined biomarker subgroups used data from a deidentified clinicogenomic database and included patients who received Foundation Medicine testing (FoundationOne or FoundationOne CDx) during routine clinical care at approximately 280 US academic or community-based cancer clinics between March 2014 and December 2021. The population included 1 cohort of patients with MSI-H MCRC who received first-line ICIs or chemotherapy and a second cohort who received ICIs in any line of therapy (LOT) for biomarker examination. ICI therapy or chemotherapy assigned at physician discretion without randomization. The main outcomes were time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Hazard ratios were adjusted for known prognostic imbalances. Comparisons of explanatory power used the likelihood ratio test. A total of 138 patients (median age, 67.0 years [IQR, 56.2-74.0 years]; 73 [52.9%] female) with MSI-H MCRC received first-line ICIs or chemotherapy. A total of 182 patients (median age, 64.5 years [IQR, 55.2-72.0]; 98 [53.8%] female) received ICIs in any LOT. Patients receiving first-line ICIs vs chemotherapy had longer TTNT (median, not reached [NR] vs 7.23 months [IQR, 6.21-9.72 months]; adjusted hazard ratio [AHR], 0.17; 95% CI, 0.08-0.35; P < .001), PFS (median, 24.87 months [IQR, 19.10 months to NR] vs 5.65 months [IQR, 4.70-8.34 months]; AHR, 0.31; 95% CI, 0.18-0.52; P < .001), and OS (median, NR vs 24.1 months [IQR, 13.90 months to NR]; HR, 0.45; 95% CI, 0.23-0.88; P = .02). MSI added to DMMR better anticipated TTNT and PFS in patients receiving ICIs than DMMR alone. The same was not observed when DMMR evaluation was added to MSI. In this comparative effectiveness research study, MSI assessed by NGS robustly identified patients with favorable outcomes on first-line ICIs vs chemotherapy and appeared to better anticipate ICI outcomes compared with DMMR.

Real-World Outcomes with First-Line Ibrutinib (Ibr) Versus Chemoimmunotherapy (CIT) in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Final Analysis Results from the InformCLL Registry

Background: The therapeutic landscape for CLL/SLL has rapidly evolved with the introduction of novel agents such as Ibr. The informCLL registry (PCYC-1134; NCT02582879) is the largest US-based prospective, observational registry of patients (pts) initiating FDA-approved treatment for CLL/SLL in the era after approval of Ibr. Here, we report real-world (RW) outcomes in pts with CLL/SLL receiving first-line (1L) therapy, including comparison of 1L Ibr versus CIT, from the final analysis of informCLL. Methods: Pts with CLL/SLL who initiated FDA-approved treatment (within ±45 days of enrollment) were enrolled between 10/2015 and 6/2019. Pts were primarily enrolled from community-based practices (comprising 93% of sites). Data were collected for baseline characteristics, treatment patterns, and safety. Time to next treatment (TTNT) was estimated by Kaplan-Meier method and for comparison of outcomes with 1L Ibr versus CIT, by Cox proportional hazards regression analysis in weighted cohorts. Inverse probability of treatment weighting (IPTW) was performed to balance the baseline characteristics between cohorts. Adverse events (AEs) were evaluated using overall incidence and exposure-adjusted incidence rates (EAIRs). Results: Of the 1459 eligible pts enrolled, 854 were treated in the 1L setting (59%). In the overall 1L cohort, median age was 70 years (≥75 years in 33%); 90% had ECOG performance status of 0 or 1; 47% had Rai stage III/IV (among n=547 with Rai staging); median Charlson Comorbidity Index (CCI) score was 1 (range 0-12) with CCI ≥3 in 16%; median time from initial diagnosis to 1L treatment was 19 mo. FISH testing data were available in 57% of pts in the 1L cohort; among these pts, 12% had del(17p). The most common 1L therapies were Ibr (45%; single-agent Ibr in 43% of all 1L therapies) and CIT (43%: most commonly BR, 24%); immunotherapy was given in 11% while chemotherapy (0.9%) and other novel agents (0.7%) were rare. With a median follow-up of 31.8 mo in the 1L cohort, median TTNT was not reached (NR); estimated proportions of pts without next-line therapy (NLT) were 79% at 24 mo, 71% at 36 mo, and 64% at 48 mo. The 1L cohort included 383 pts treated with Ibr and 363 pts treated with CIT; median follow-up was 31.4 mo for the Ibr cohort and 34.3 mo for CIT. Compared with the CIT cohort, pts in the Ibr cohort were older, had longer time from diagnosis to treatment, were more likely to have a history of other malignancy, and were more likely to have del(17p) or TP53 mutation (Table). Baseline characteristics in the weighted cohorts were balanced. In the IPTW-adjusted cohorts, median TTNT was NR for Ibr and 56.5 mo for CIT; TTNT was improved with Ibr relative to CIT (hazard ratio 0.744; 95% CI, 0.563-0.981) (Figure). Estimated proportions free of NLT in the weighted Ibr cohort were 75% at 36 mo and 69% at 48 mo; rates in the weighted CIT cohort were 66% and 57%, respectively. Median duration of index treatment was 24.0 mo for 1L Ibr and 4.7 mo for CIT. In the Ibr cohort (n=383), serious AEs occurred in 144 pts (38%), most commonly (≥3% of pts) pneumonia (n=23; 6%) and atrial fibrillation (Afib; n=21; 5%); AEs led to discontinuation of Ibr in 135 pts (35%), most commonly Afib (n=19; 5%) and fatigue (n=12; 3%). In the CIT cohort (n=363), serious AEs occurred in 85 pts (23%), most commonly febrile neutropenia (n=13; 4%) and pneumonia (n=11; 3%). AEs led to discontinuation of CIT in 61 pts (17%), and no single AE term led to discontinuation in ≥3% of pts (most common was anemia, 2%). EAIRs per 100 pt-mo for serious AEs were 1.93 with Ibr and 4.55 with CIT. EAIRs per 100 pt-mo for AEs leading to discontinuation were 1.53 with Ibr and 3.09 with CIT. Conclusion: In this large RW registry of pts with CLL/SLL, results from IPTW-adjusted analysis showed that 1L Ibr was associated with longer TTNT than CIT, with sustained benefit up to 4 years of follow-up. Pts receiving 1L Ibr therapy tended to be older, more often had a history of other malignancy, and more often had high-risk genomic features (del(17p) or TP53 mutation among those tested) than pts treated with CIT. The spectrum and frequency of AEs observed with these 1L regimens appear consistent with data from clinical studies and other RW studies. When adjusted for exposure, rates of AEs leading to discontinuation and serious AEs were lower with Ibr than CIT. Future analyses examining the impact of factors such as age/comorbidity and race are warranted to further our understanding of RW outcomes in pts with CLL/SLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Outcomes of Second-Line Chronic Lymphocytic Leukemia Treatments: Retrospective Analysis of the Brazilian Registry of CLL

Introduction: Major advances in the treatment of relapsed-refractory (RR) chronic lymphocytic leukemia (CLL) patients were observed in the last decade with the adoption of targeted agents. While a shift away from chemotherapy is expected, the impact of delayed or unequal access to targeted agents in low- and middle-income countries needs to be uncovered through real-world data. Objective: To assess the clinical outcomes of second-line treatment in RR CLL patients included in the Brazilian Registry of CLL (BRCLL). Patients and Methods: This is an observational study of second-line CLL treatments started between January 2006 and December 2021. BRCLL is a prospective non-interventional data collection tool. All participant centers registered their CLL patients online, after study approval at each center's ethical review board. Diagnosis and staging of included CLL patients were performed in accordance with recommendations from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL). Results: Four hundred and forty-four CLL patients in second-line were included. Median age at start of second-line treatment was 66 years (range: 23-93), and 264 were male (59%). At CLL diagnosis, Binet staging was A in 139 patients (36%), B in 139 (36%), and C in 107 (28%). High beta-2-microglobulin levels at diagnosis were found in 58%, and unmutated IGHV was observed in 61% of patients. At diagnosis, FISH was performed in 166 patients (37%), of which 33 patients had del(17p) (20%). The most commonly prescribed second-line treatments were: FC (+/- R) in 160 patients (36%); chlorambucil (+/- R) in 109 (25%); ibrutinib in 63 (14%); CHOP/CVP (+/- R) in 62 (14%); monoclonal antibodies (+/- steroids) in 33 (7%); allogeneic stem cell transplantation in 9 (2%) and venetoclax in 8 (2%). Forty patients (9%) were treated in clinical trials. Median follow-up after second-line treatment was 34 months (range: 3-176). Median time-to-next treatment (TTNT) was 28 months. TTNT was statistically longer in patients who received second-line with ibrutinib or venetoclax in comparison with FC or chlorambucil +/- anti-CD20 (not reached versus 29 months, p<0.0001) or those who received other regimens (CHOP or CVP +/- anti-CD20, monoclonal antibodies +/- steroids - 12 months, p<0.0001). Higher 3-year treatment-free survival (TFS) was also observed with ibrutinib or venetoclax (69% versus 41% and 23%, respectively, p<0.0001). Among patients included in clinical trials, 3-year TFS was also higher (70% versus 38%, p<0.0001). TFS for patients receiving allogeneic stem cell transplantation was 86% at 3 years. Overall survival (OS) probability at 3 years was 71%. OS was significantly shorter in those who received other regimens (CHOP/CVP-like or monoclonal antibodies +/- steroids - 53%), in comparison with those who received ibrutinib or venetoclax (80%, p<0.0001), or FC/chlorambucil-based chemotherapy (69%, p=0.01). Conclusion: Over the reported period, second-line CLL treatments in Brazil were mostly chemotherapy- or chemoimmunotherapy-based, with unfavorable outcomes associated with CHOP/CVP-like regimens or monoclonal antibodies +/- steroids. While the adoption of targeted therapies was associated with longer TTNT and OS, access to these agents is still very limited in the public setting.

OUTCOMES OF SECOND-LINE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): RETROSPECTIVE ANALYSIS OF THE BRAZILIAN REGISTRY OF CLL

Real-world data from low and middle-income countries on the management of chronic lymphocytic leukemia (CLL) is needed to understand current clinical practices and unmet needs. Delayed or unequal access to novel agents may negatively impact disease outcomes in (RR) CLL. To describe clinical outcomes of second-line treatment in patients with CLL included in the Brazilian Registry of CLL (BRCLL). Observational study of second-line CLL treatments started between 2006 and 2021. BRCLL is a prospective non-interventional data collection tool. All participant centers registered their CLL patients online, after study approval at each center's ethical review board. Second-line treatments for 444 CLL patients were included. Median age at start of second-line treatment was 66 years (range: 23-93), and 264 were male (59%). Binet staging at CLL was A in 139 patients (36%), B in 139 (36%), and C in 107 (28%). Unmutated IGHV was observed in 61% of patients and FISH was performed in 166 patients (37%), of which 33 patients had del(17p) (20%). The most commonly prescribed regimens were: FC (+/- R) in 160 patients (36%); chlorambucil (+/- R) in 109 (25%); ibrutinib in 63 (14%); CHOP/CVP (+/- R) in 62 (14%); monoclonal antibodies (+/- steroids) in 33 (7%); allogeneic stem cell transplantation in 9 (2%) and venetoclax in 8 (2%). Forty patients (9%) were treated in clinical trials. Median follow-up after second-line treatment was 34 months (range: 3-176). Median time-to-next treatment (TTNT) was 28 months. TTNT was statistically longer in patients who received second-line with ibrutinib or venetoclax in comparison with FC or chlorambucil +/- anti-CD20 (not reached versus 29 months, p < 0.0001) or those who received other regimens (CHOP or CVP +/- anti-CD20, monoclonal antibodies +/- steroids – 12 months, p < 0.0001). Higher 3-year treatment-free survival (TFS) was also observed with ibrutinib or venetoclax (69% versus 41% and 23%, respectively, p < 0.0001). Among patients included in clinical trials, 3-year TFS was also higher (70% versus 38%, p < 0.0001). TFS for patients receiving allogeneic stem cell transplantation was 86% at 3 years. Overall survival (OS) probability at 3 years was 71%. OS was significantly shorter in those who received other regimens (CHOP/CVP-like or monoclonal antibodies +/- steroids; 53%), in comparison with those who received ibrutinib or venetoclax (80%, p < 0.0001), or FC/chlorambucil-based chemotherapy (69%, p = 0.01). Chemotherapy-based second-line CLL treatments were frequent over the reported period, with inferior outcomes for CHOP/CVP-like treatments and monoclonal antibodies with or without steroids. Considering the approval of Bruton tyrosine kinase and BCL2 inhibitors in recent years, a shift towards targeted agents in RR CLL is anticipated, but cannot be established at this time for the majority of patients in second line reported to the BRCLL. While the adoption of targeted therapies was associated with longer TTNT and OS, access to these agents is still very limited in our setting.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21days (range, 0-341days) and 50days (range, 1-352days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n=134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P=.039). CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Cytogenetic abnormalities in MM: Association with disease characteristics and treatment response.

e20520 Background: Cytogenetic abnormalities detected by FISH are found in the majority of multiple myeloma (MM) patients. Although their prognostic value has been studied extensively, less is known about their association with disease characteristics and treatment response. Methods: To address these questions, we designed a retrospective study including 2031 Mayo Clinic patients diagnosed with MM from 2004 to 2018. We compared baseline characteristics and treatment outcomes between primary cytogenetic groups: t(11;14), t(4;14), t(14;16), (14;20), t(6;14), unknown IgH translocation/del and trisomy (without IgH translocation). These included 373, 177, 78, 20, 18, 228 and 791 patients respectively. Kruskal-Wallis and Fisher’s exact tests were used for categorical and continuous variables respectively. Time to next treatment (TTNT) was estimated using Kaplan-Meier method and compared using Log-Rank test. Results: t(4;14), t(14;16), t(6;14) and t(14;20) groups were associated with hemoglobin &lt; 10 g/dL, beta2microglobulin &gt; 5.5 µg/ml, ISS stage 3 and ≥50% bone marrow plasma cells. The latter 3 groups were also associated with renal dysfunction (Cr ≥2 mg/dL) and higher urinary monoclonal protein. t(4;14) was associated with IgA isotype, serum monoclonal protein ≥1g/dL and plasma cell labeling index ≥1%. Light chain myeloma was more prevalent in patients with t(11;14). Overall response rate (ORR) to proteasome inhibitor (PI) induction was higher for those with IgH translocations (any) compared to trisomies (85% vs 77% P = 0.02), while ORR was higher for those with trisomies with immunomodulatory drug (IMiD) induction (90% vs 78% P &lt; 0.01). The rate of ≥ very good partial response was higher for patients with high risk IgH translocations [t(4;14), t(14;16) or t(14;20)] compared to standard risk with PI-IMiD combination treatment (88% vs 65% P &lt; 0.01). Otherwise, response rates did not differ between these 2 groups. TTNT was longer in patients with trisomies compared to those with IgH translocation with IMiD or PI-IMiD treatments (32.2 vs 19 and 44 vs 27.4 months, respectively P &lt; 0.01). For all cytogenetic groups, better treatment responses and longer TTNT were seen with PI-IMiD combinations compared to other treatments. Conclusions: t(4;14), t(14;16), t(6;14), and t(14;20) are associated with high risk disease characteristics. Patients with IgH translocations may have better response to PI induction compared to those with trisomies, while those with trisomies may have better response to IMiD treatment, with best outcomes for both seen with PI-IMiD combinations.

A real-world comparative analysis of pomalidomide (POM) and other antimyeloma treatments following lenalidomide (LEN) discontinuation among patients with multiple myeloma.

e19337 Background: In clinical trials, POM has demonstrated favorable clinical outcomes in patients with multiple myeloma (MM) who received prior LEN. Few studies, however, have examined POM treatment for MM in the community oncology setting. This retrospective cohort study compared treatment patterns and outcomes between patients who received a post-LEN treatment, either POM or another antimyeloma regimen. Methods: Adult patients with MM in the US Oncology Network (USON) who initiated a post-LEN treatment within 60 days of LEN discontinuation between Jan 1, 2016 and May 1, 2018, were not clinical trial participants, and had ≥ 2 subsequent clinic visits, were eligible. Data were sourced from USON’s iKnowMed electronic health records. Among patients observed to have discontinued treatment, time to treatment discontinuation (TTTD) was estimated from date of initiation of post-LEN treatment (index treatment) to date of discontinuation. Among patients who started a new treatment after the index treatment, time to next treatment (TTNT) was estimated from date of initiation of index treatment until date of initiation of the next treatment. TTTD and TTNT were analyzed using the Kaplan–Meier (KM) method across the whole study sample; patients who did not discontinue or start a next treatment were censored. Results: Of 547 eligible patients, 155 (28.3%) initiated POM and 392 (71.7%) initiated another antimyeloma regimen. Demographic characteristics were similar between the groups (for all patients, median age was 68 years, 54.5% patients were male and 71.7% were white). In total, 74.2% and 83.7% of patients discontinued the index treatment in the POM and other-treatment groups, respectively. Among the entire study population, KM estimates of median TTTD were 3.5 months (95% CI 2.8–4.6) and 1.9 months (95% CI 1.6–2.4) in the POM and other-treatment group, respectively (log-rank P &lt; 0.001). In total, 65.2% and 71.2% of patients initiated subsequent treatment in the POM and other-treatment groups, respectively. KM estimates of median TTNT were 6.2 months (95% CI 4.5–7.8) and 4.5 months (95% CI 3.9–5.3) in the POM and other-treatment groups, respectively (log-rank P = 0.38). Conclusions: For patients with MM the use of POM following LEN treatment resulted in longer TTNT and TTTD compared with those who received other antimyeloma therapy. These findings support the use of POM treatment after LEN as an option for patients with relapsed/refractory MM.

HORIZON (OP-106): An exploratory analysis of time-to-next treatment (TTNT) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who received melflufen plus dexamethasone (dex).

e20570 Background: Melflufen is a novel peptide-drug conjugate that rapidly delivers a cytotoxic payload into tumor cells. Melflufen + dex showed efficacy and a manageable safety profile in pts with poor-risk, heavily pretreated RRMM in the phase 2 HORIZON study (Mateos et al. ASH 2019. Abs. 1883). For pts with RRMM, longer TTNT is indicative of disease stabilization and clinical benefit and is associated with lower costs (Chen et al. J Manag Care Spec Pharm. 2017). This report of TTNT after melflufen + dex from HORIZON is, to our knowledge, the first report from a trial population with such advanced RRMM. Methods: Pts with RRMM who had received ≥2 prior lines of therapy, including an IMiD and a proteasome inhibitor (PI), and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody (mAb), received melflufen 40 mg (IV on d1 of each 28-d cycle) + dex 40 mg/wk until disease progression or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival (PFS) and safety. TTNT was defined as the time from start of melflufen + dex to first subsequent therapy. Results: Overall, 154 pts were treated (data cutoff, Oct 1, 2019); median age was 64.5 y (range, 35-86), 32% had International Staging System stage 3 disease, 38% had high-risk cytogenetics, 32% had extramedullary disease (EMD), the median number of prior therapies was 5 (range, 2-12), and 71% had triple-class refractory MM (IMiD + PI + anti-CD38 mAb). Treatment discontinuation occurred in 108 pts (70%), most commonly due to disease progression (47%) and adverse events (14%). Among 125 pts evaluable for response, with a median follow up of 15.3 mo, the median TTNT was 8.0 mo (95% CI, 7.2-8.9) and the median PFS was 4.2 mo (95% CI, 3.7-4.9). TTNT and PFS were similar in subgroups of pts with triple-class refractory MM and EMD (Table). Subsequent therapies after melflufen + dex will be presented. Conclusions: TTNT in HORIZON (median 5 prior lines) was consistent with previous reports of TTNT in pts with RRMM who received melflufen + dex or other therapies (median 2-4 prior lines) (Bringhen et al. J Clin Oncol. 2019. Abs. 8043). Melflufen + dex is being further evaluated in the phase 3 OCEAN study (NCT03151811) in pts with RRMM who are refractory to lenalidomide. Clinical trial information: NCT02963493. [Table: see text]

Lenalidomide maintenance post-transplantation in newly diagnosed multiple myeloma: real-world outcomes and costs.

Aim: To compare real-world outcomes and costs among patients with newly diagnosed multiple myeloma receiving lenalidomide-only maintenance (Len-Mt) versus no maintenance after autologous hematopoietic stem cell transplantation. Patients & methods: Time to next treatment (TTNT) was evaluated; costs were calculated for 0-12, 12-24 and 24-36 months postindex date. Results: Len-Mt cohort had longer TTNT (HR: 0.43; p < 0.0001). Per-patient per-month costs during months 0-12 were higher among patients, receiving Len-Mt (USD 13,095 vs USD 8910; p < 0.0001), due to higher pharmacy costs - outpatient costs were lower. During months 12-24 and 24-36, outpatient costs were similar in both cohorts; total and pharmacy costs remained elevated for patients receiving Len-Mt. Conclusion: Len-Mt improved TTNT, initially reduced outpatient costs, but resulted in higher overall and pharmacy costs.

The Impact of First Complete Remission by PET-CT and Time to Next Treatment on Survival of Follicular Lymphoma Patients

We retrospectively analyzed the impact of initial positron emission tomography and computed tomography (PET-CT) complete remission (CR) and time to next treatment (TTNT) on patient outcome in follicular lymphoma. Between 2002 and 2014, 150 patients could be evaluated for treatment response and long-term outcome. The CR after first line treatment with either rituximab-cyclophosphamide, oncovin, and prednisolone (R-COP) or rituximab-cyclophosphamide, doxorubicin, oncovin, and prednisolone (R-CHOP) was 89% and partial response (PR) was 7%. The 5- and 10-year survival rates were 86.0% and 62.6%, respectively. In five years, 11% of patients had died of lymphoma and 3% from other causes. Forty-seven patients (31%) underwent a second line of treatment comprising 19 (40%) with a TTNT shorter than 24 months and 28 (60%) longer than 24 months. There was no difference in overall survival (OS) between R-COP (86%) and R-CHOP (77%) at 5 years, but there were more next treatment events in the R-COP compared with the R-CHOP group on longer follow-up (60% versus 35% at 8 years). For PET-CT response, there was a significant OS difference between initial CR and PR patients (88% versus 70%, p < 0.01), and a longer TTNT was seen in initial CR patients. Patients with a TTNT longer than 24 months had better OS compared with patients with a shorter TTNT (93% versus 54% at 5 years, p < 0.01). In conclusion, patients with initial PET-CT CR and TTNT longer than 24 months had better OS compared with those achieving only PR and shorter TTNT. PET-CT CR should be considered the treatment goal during initial treatment, and more aggressive treatment should be considered for patients with a TTNT of less than 24 months.

Comparison of Time to Next Treatment, Health Care Resource Utilization, and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy

BackgroundStudies assessing ibrutinib’s economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT. Materials and MethodsOptum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted. ResultsTTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib’s higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = −$10,615; P < .0001), yielding net savings (MMCD = −$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = −$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy. ConclusionDuring front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.

Treatment Patterns and Clinical and Economic Outcomes in Patients With Newly Diagnosed Multiple Myeloma Treated With Lenalidomide- and/or Bortezomib-containing Regimens Without Stem Cell Transplant in a Real-world Setting

BackgroundReal-world data in patients with newly diagnosed multiple myeloma (NDMM) are sparse. Using United States claims databases, we analyzed treatment patterns, clinical outcomes, and health care utilization and costs in patients receiving lenalidomide- and/or bortezomib-containing therapy. Materials and MethodsPatient claims were obtained from a large commercial and Medicare database (October 2009 to May 2015). Patients with NDMM who received lenalidomide- and/or bortezomib-containing therapy and did not receive stem cell transplant (SCT) were analyzed. Duration of treatment (DOT), time to next treatment (TTNT), and health care utilization and costs were evaluated. ResultsOf 3075 patients, 1767 received doublet therapy (814 lenalidomide-dexamethasone [Rd], 953 bortezomib-dexamethasone [Vd]) and 464 received triplet therapy (318 lenalidomide-bortezomib-dexamethasone [RVd], 146 cyclophosphamide-bortezomib-dexamethasone [CyBord]). Rd versus Vd resulted in longer median DOT (12.0 vs. 5.9 months; P < .0001) and median TTNT (36.7 vs. 24.4 months; P = .0005). Year 1 costs were greater with Rd versus Vd (Δ = $14,964; P = .0009), primarily owing to higher pharmacy costs; outpatient physician visits and chemotherapy administration costs were lower. Median DOT (14.8 vs. 9.0 months; P < .0001) and median TTNT (35.7 vs. 22.3 months; P = .0007) were longer with RVd versus CyBord; year 1 costs were comparable. ConclusionsIn this study of patients with NDMM ineligible for transplant, the median duration of therapy was approximately 70% of that in clinical trial observations. Lenalidomide therapy versus Vd and CyBord resulted in longer DOT, which correlated with longer TTNT, and higher pharmacy costs, which were partially offset by lower outpatient and chemotherapy administration costs.