Initiation Of New Therapy Research Articles

P344 Achieving Crohn's Disease treatment targets following the STRIDE-II recommendations in clinical practice

Abstract Background The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative proposes therapeutic targets for inflammatory bowel disease (IBD) to be used for a treat-to-target clinical management strategy. However, there is lack of information regarding how many patients actually achieve defined treatment targets as outlined in STRIDE-II after initiation of new therapies. The objective of this study was to investigate the treatment response of Crohn’s disease (CD) patients according to the STRIDE-II recommendations in the first year after starting a new pharmacological therapy in clinical practice. Methods CD patients included in a remote monitoring care-path using myIBDcoach, starting a new therapy between January 1st 2020 and December 31st 2021 were eligible for inclusion. The short-term (2-4 months) treatment target was defined as clinical response based on at least 50% decrease in the Monitor IBD at home (MIAH) questionnaire, a patient-reported outcome measure validated to predict endoscopic disease activity. Intermediate (5-9 months) targets were clinical remission (MIAH ≤3.6) and normalization of inflammatory parameters, i.e. faecal calprotectin (<150 ug/g) and C-reactive protein ([CRP] <10 mg/L). Long-term (10-12 months) targets were absence of disability (IBD-control questionnaire ≥13), and a combination of MIAH score ≤3.6 and calprotectin <150 ug/g as surrogate markers for endoscopic remission. Results 39 CD patients were included in the current analysis, of which two started treatment with thiopurines and 37 with a biological. At baseline, median MIAH score was 3.0 (IQR 3.1) and median IBD-control score was 8.5 (IQR 9.0). After three months of therapy, 26% of patients showed clinical response and 64% of patients were in clinical remission (median MIAH 2.2 [IQR 1.8]). As for intermediate targets, clinical remission was seen in 62% (median MIAH 2.0 [IQR 2.3]), and CRP and calprotectin normalization in 79% and 59% of patients, respectively. At the end of follow-up, 41% had low surrogate marker scores indicative for endoscopic remission (median MIAH 1.9 [IQR 1.6] and median calprotectin 109.0 [IQR 241.0]). Resolution of disability was achieved in 65% (median IBD-control score 14.0 [IQR 6.0]). Three patients (9%) achieved all treatment targets within a year of follow-up (Table 1). Conclusion This study used an incident user real-world cohort to evaluate the STRIDE-II recommendations. While all patients achieved at least one treatment target, only 9% achieved all treatment targets according to the STRIDE-II recommendations. Using these recommendations provides good guidance in clinical settings. However, treatment approaches need to be improved to reach the optimal outcomes in daily clinical practice.

Endpoints in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

We observed lack of clarity and consistency in end point definitions of large randomized clinical trials in diffuse large B-cell lymphoma. These inconsistencies are such that trials might, in fact, address different clinical questions. They complicate interpretation of results, including comparisons across studies. Problems arise from different ways to account for events occurring after randomization including absence of improvement in disease status, treatment discontinuation or the initiation of new therapy. We call for more dialogue between stakeholders to define with clarity the questions of interest and corresponding end points. We illustrate that assessing different end point rules across a range of plausible patient journeys can be a powerful tool to facilitate such a discussion and contribute to better understanding of patient-relevant end points.

Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light-Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network

Introduction Patients (pts) with Mayo stage 3B light-chain (AL) amyloidosis have high risk of early death, mainly due to severe cardiac dysfunction. The ANDROMEDA study showed that pts with newly diagnosed (ND) AL amyloidosis, daratumumab (dara) combined with bortezomib-cyclophosphamide-dexamethasone (D-VCd) induced high rates of hematologic complete response (CR); however, pts with Mayo stage 3B were excluded. Dara's high single agent activity and favorable toxicity profile makes it an attractive option for stage 3B AL amyloidosis pts. This prospective study evaluated the efficacy and safety of dara monotherapy in stage 3B NDAL pts. Methods EMN22, a phase 2, open-label, multinational study (NCT04131309) enrolled 40 NDAL pts with stage 3B disease. Eligible adult pts had serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥8500 pg/mL and high-sensitivity troponin T (hsTnT) >54 pg/mL. Dara monotherapy was initially administered intravenously (16 mg/mL), and after February 2020 subcutaneously as a fixed dose of 1800 mg weekly (QW) during cycles (C)1-2, Q2W for C3-6, and Q4W thereafter. Pts not achieving ≥hematological very good partial response (VGPR) by C4 could receive additional bortezomib QW and low-dose dexamethasone (Vd). Treatment continues for up to 2 years from initiation or until progressive disease (PD) or initiation of new therapy. The primary endpoint was the overall survival (OS) rate at 6 months, aiming for a 6-month OS rate of ≥50%. Results The study completed accrual and 40 pts were enrolled (median age: 70.5 years [range 45.0-86.0]; male: 22 [55.0%]). At cut-off (31/05/2023), 6 (15.0%) pts continued treatment, 26 (65.0%) had discontinued, and 8 (20.0%) had completed treatment. At screening, 25 (62.5%) pts had ECOG status ≥2, and 16 (40.0%) and 24 (60.0%) pts had New York Heart Association class II and IIIA symptoms, respectively. The median (range) NT-proBNP, hsTnT and difference of involved to uninvolved free light chains were 14,353 (8,516-72,522) pg/mL, 136 pg/mL (55-692), and 430 mg/L (40-2820) respectively. At baseline (C1, day 1), besides the heart, 33 (82.5%) pts had ≥1 organs involved, most frequently the kidneys (20/40 pts, 50%) and peripheral nerves (12/40 pts, 30%). At a median (range) follow-up of 10.1 months (<0.1-43.6), the median (range) number of dara administrations was 18 (1-36) and treatment duration was 6.6 months (<0.1-25.3). Ten (25.0%) pts received additional Vd treatment. The 6-month OS rate (primary end point) was 65.0% (95% CI) (48.2-77.6); the 3-month OS was 72.5% (55.9-83.7) and median OS was 10.3 months (4.1-32.1) ( Figure). At 6 months, a hematologic response (≥partial response [PR]) was achieved by 31 (77.50%) pts (CR: 5 [12.5%]; VGPR: 15 [37.5%]; PR: 11 [27.5%]) ( Table). Within 3 months of treatment initiation 28 (70.0%) pts had achieved a response. Median duration of hematologic response was not reached. Pts achieving ≥PR at 3 months had a higher post-3-months median (95% CI) OS compared to pts with <PR (29.10 [8.34-NR]; 5.8 [0.38-NR], respectively). Any organ response at 3 or 6 months was achieved by 10 (25.0%) and 13 (32.5%) pts, respectively; a cardiac response at 3- and 6-months was achieved by 9 (22.5%) and 11 (27.5%) pts, respectively ( Table). All pts experienced ≥1 adverse event, either serious (SAE) or non-serious (NSAE). Thirty-eight (95.0%) pts had ≥1 NSAE. Grade (Gr) 3/4 NSAEs occurred in 21 (52.5%) pts, commonly dyspnea and peripheral edema (4 [10.0%] pts each). Of all pts, six (15.0%) experienced treatment related Gr3/4 NSAEs, including Gr3 neutropenia and lymphopenia (1 [2.5%] each) related to dara and a Gr3 troponin increase (1 [2.5%]) related to bortezomib. Thirty-one (77.5%) pts had ≥1 SAE, including 17 (42.5%) pts with cardiac disorders. Seventeen (42.5%) pts had fatal SAEs, mostly to cardiac disorders (9 [22.5%]); 14 (35.0%) were ongoing and 3 (7.5%) had discontinued. Treatment-related SAEs occurred in 6 (15.0%) pts and dara-related SAEs in 4 (10.0%) pts. Conclusions In high-risk (stage 3B) AL amyloidosis pts, dara monotherapy induced early and profound hematologic responses over 6 months with 77.5% of pts achieving ≥PR and 50% VGPR/CR, and cardiac responses were seen in 27.5% of pts. No new safety (cardiac) concerns were observed and the primary objective of the study was met. Based on these results, dara monotherapy should be considered as an active and relatively non-toxic treatment option for stage 3B pts with AL amyloidosis.

Clinical Outcomes with Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer: Results from a Prospective Registry Trial

Metastasis-directed radiation therapy using stereotactic body radiation therapy (SBRT) in oligometastatic prostate cancer (Oligo PCa) has a demonstrated benefit for local control and biochemical recurrence free survival for men with oligorecurrent PCa; however, the impact of SBRT within other oligometastatic states and in the context of systemic therapy remains poorly characterized. In this study, we investigate prognostic factors for clinical outcomes in a prospective cohort of Oligo PCa patients treated with metastasis-directed SBRT. Using a single-institution registry trial, we analyzed a prospective cohort of 86 patients with Oligo PCa (≤5 metastatic lesions) and treated with metastasis-directed SBRT between 2017- 2022. Patients were classified as synchronous, metachronous, or induced oligometastatic disease as per the ESTRO guidelines. We evaluated the time to radiographic progression (TTRP), defined as the time from SBRT start date to radiographic progression, as well as time to initiation of new treatment (TTNT), defined as the time from SBRT end date to initiation of new therapy (systemic or radiation therapy). Time to event (TTE) was defined as the time from SBRT start date to radiographic progression or initiation of new therapy, whichever occurred first. Patients without documented events were censored at the date of last disease assessment. Comparative analyses were performed using Kaplan-Meier and Cox proportional hazards regression methods. Eighty-six men with Oligo PCa treated with SBRT were followed for a median of 16.4 months with M0 (73%), Oligo PCa (21%) or polymetastatic PCa (6%) GS > = 8 (63%) at initial diagnosis. At the time of treatment with initial SBRT, 21% had synchronous oligometastatic disease, 63% had metachronous or repeat oligorecurrence or oligoprogression, and 16% had induced oligometastatic disease. Most patients were treated to 1-3 sites (94%), which predominantly included bone (86%), and the median dose was 35 Gy/5F. Concurrent systemic therapy during SBRT was seen in 85% of patients, including (60.5% with new generation androgen receptor signaling inhibitors). Overall survival at 1-year and 2-years was 96.9% [95% CI, 88.2-99.2%] and 94.4% [95% CI, 83.2-98.2%]. Using univariable analysis, those who did not receive systemic treatment during SBRT had significantly shorter TTRP (HR 3.67, [95% CI, 1.62-8.32], p = 0.002), TTNT (HR 3.24, 95% CI [1.49-7.06], p = 0.003), and TTE (HR 3.05, [95% CI, 1.44-6.45], p = 0.004). Additionally, patients treated with SBRT for metachronous (HR 2.89, [95% CI 0.68-12.30]) and induced metastatic disease (HR 8.96, [95% CI 1.85-43.37]) had significantly shorter TTE compared to synchronous oligometastatic disease (p = 0.006). Using a prospective registry cohort of men with Oligo PCa treated with SBRT, we identify an association of oligometastatic state and the use of concurrent systemic therapy with improved TTRP and TTNT. Further prospective studies are warranted.

Tracking changes in circulating stromal cells and circulating tumor cells predicts responsiveness of new line induction in metastatic breast cancer after 1 cycle of therapy.

3056 Background: In metastatic Breast Cancer (mBC), Circulating Tumor Cells (CTCs) are established prognostic indicators of patients (pts) not responding to new lines of therapy and who have poor clinical outcomes. However, CTCs are typically found in < 20% of mBC pts and many pts without CTCs will also progress. Recently an inflammatory pro-tumorigenic macrophage emanating from tumor stroma (i.e. Cancer associated macrophage-like cell [CAML]) was found in > 90% of mBC pts and were also indicative of poor clinical outcomes. As CTCs & CAMLs are isolated in conjunction from a single blood sample, and both are prognostic for therapy response, we evaluated CTCs & CAMLs before and after initiation of new therapies in mBC to determine their combined prognostic/predictive values. Methods: An observational prospective 2-year multi-institutional study was undertaken to evaluate CTCs & CAMLs before, and after, induction of any new line of therapy in pts with diagnosed mBC (n = 101). Anonymized and blinded blood samples were taken at baseline (BL), prior to starting a new systemic therapy, and a 2nd sample (T1) taken after therapy initiation (̃30 days). Blood was filtered by CellSieve filtration. The quantities and subtypes of CTCs & CAMLs were analyzed based on RECIST v1.1 for progression-free survival (PFS) and overall survival (OS) hazard ratios (HRs) by censored univariate & multivariate analysis at 2 years. Results: CTCs were identified in 35% (n = 35/101) of pts at BL & 24% (n = 24/101) at T1, with a single CTC at T1 being highly prognostic for worse PFS HR = 6.2 95%CI 3.0-13.2, p < 0.001 & OS (HR = 5.1 95%CI 2.0-13.4, p = 0.002. In parallel, CAMLs were found in 93% of BL and 86% of T1 samples, and whose decreases were significantly prognostic for improved PFS (HR = 2.7, 95%CI 1.4-5.1, p = 0.006) and OS (HR = 4.4 95%CI 1.5-13.2, p = 0.018) when CTCs were absent. Overall ≥1 CTC at T1 (n = 24) had median PFS = 2.4 & mOS = 4.8 months (mos), however, in pts without CTCs plus an increase in CAMLs (n = 36) had mPFS = 5.9 & mOS = 14.1 mos, while in pts without CTCs plus a decrease in CAMLs (n = 41) had mPFS = 14.8 & mOS = 18.8 mos. Conclusions: Our data confirms that pts with persistent CTCs have the worst clinical outcomes. Further, simultaneous CAML quantification provided a new dynamic predictive blood based biomarker in pts without detectable CTCs which may be useful to better individualize therapy and improve outcomes, though future studies are need to validate these findings.

Medication Therapy Management for Texas MediCAID Patients With Asthma and Chronic Obstructive Pulmonary Disease—A Pilot Study

Background: Pharmacists can play an important role in providing medication therapy management (MTM) services, which focus on appropriate medication use. This pilot study aimed to describe pharmacists’ MTM service provision, results/outcomes of pharmacists’ recommendations and resolution/acceptance rate among patients with high-risk asthma and/or chronic obstructive pulmonary disease (COPD). Methods: This was a prospective descriptive study of MTM services provided by community pharmacists to Texas Medicaid patients (5-63 years) with “high risk” asthma or COPD. Patients received in-person and telephone consultations that included medication review, asthma control test assessment, and education on adherence and proper medication/device use. Data extracted from MTM software was used to describe: reasons for MTM services, type of pharmacists’ interventions, outcomes of pharmacists’ recommendations and acceptance rate. Results: Twenty-eight pharmacists provided 139 MTM interventions with 63 patients (2.2 interventions per patient). The most frequent intervention reason was complex drug therapy (53.2%), underuse of medication (8.6%), need for drug therapy (8.6%), new or changed prescription therapy (6.5%), and administration technique (5.0%). The resolution rate was 77.7%. Patient and prescriber, respectively, refused recommendation in 12% and 6% of the interventions. Outcomes included comprehensive medication review (46.7%), improved adherence (6.5%), therapeutic success (6.5%), improved administration technique (5.0%), and initiation of new therapy (5.0%). Conclusion: Through the provision of MTM, pharmacists were able to identify and intervene with medication-related problems. These interventions are instrumental in helping patients better manage their asthma/COPD. The high resolution rate was encouraging. Larger scale studies are needed to assess clinical and economic outcomes.

The role of cardiovascular assessment in low risk thyroid neoplasm patients: results from a tertiary care center experience

<p class="abstract"><strong>Background:</strong> After surgery, clinical approach to thyroid neoplasms often involves TSH suppression. An increased cardiovascular (CV) risk due to thyroid hormones excess has already been proved. Aim of the study was to evaluate the role of CV assessment in preventing new events and optimizing the follow-up of these patients.</p><p class="abstract"><strong>Methods:</strong> After thyroidectomy for low risk thyroid neoplasms, a cohort of 108 women was retrospectively evaluated. A first examination (V1) at the end of primary treatments and a second one (V2) five years later were considered. Clinical and echocardiographic evaluations were performed in each examination. Patients were divided into 3 subclasses depending on TSH-suppression degree in the study period. New cardiovascular events, initiation of new therapies and cardiovascular deaths were recorded. </p><p class="abstract"><strong>Results:</strong> The incidence of CV events was 7,4%. Patients age (p=0.032), previous CV events (p=0.001), use of lipid-lowering (p=0.002) and antiplatelet (p=0.027) drugs and diabetes mellitus (p=0,049) were associated with total CV events; interventricular septum thickness, BMI and tryglicerides value with ischaemic events (sensitivity 66,6%, 100%, 80%; specificity 91,1%, 55,1%, 77,2%, respectively; p<0.001); TSH-suppression class with arrhythmic events (p=0.035); an increased left ventricular mass index ratio between V2 and V1 with both total (p=0.001) and ischaemic (p=0.002) CV events.</p><p class="abstract"><strong>Conclusions:</strong> After primary treatments for thyroid neoplasm, a complete CV assessment is advisable in defining TSH-suppression target. Ultrasound parameters appear useful in evaluating CV risk both at baseline and during the follow-up. A periodic revaluation of those parameters may allow the prevention or early diagnosis of new events and complications.</p>

A Single Center Review Evaluating Daratumumab Outcomes in Multiple Myeloma Patients at Monter Cancer Center/Northwell Health Cancer Institute

Multiple myeloma (MM) is a malignant neoplasm of plasma cells in bone marrow. Daratumumab (Dara) is a CD38-directed antibody which is Food and Drug Administration (FDA) approved for treatment of patients with MM. Dara is recommended by the National Comprehensive Cancer Network (NCCN) guidelines, which many community oncologist use as the standard of care guidelines. Therefore, we consider it important to analyze Dara use and effects in the real-world community Oncology clinic setting. We evaluated the survival outcomes, both progression-free survival (PFS) and overall survival (OS), as well as the time to progression (TTP) of MM and common adverse events (ADEs) seen in patients at a single site, Monter Cancer Center in the Northwell Health (NH) system. This is a single group study evaluating outcomes of patients with MM who received Dara at NH. Primary objectives include evaluating OS, defined as time from initiating Dara therapy to time of death from any cause. Secondary objectives include PFS, time from initiation of Dara therapy to documented disease progression. We also plan to evaluate time to next treatment (TTNT), TTP and rate of ADEs within 30 days of initiating Dara. This is a retrospective study of patients with MM who received Dara at Monter Cancer Center, Northwell Health Cancer Institute. Basic demographics; gender, age at diagnosis, body mass index (BMI), and ethnicity, were collected. Treatment information collected included, previous number of therapies, dose of Dara in total and per body weight in kg, number of doses of Dara received. Data was collected using electronic medical records from January 2015 through December 2019. Patient charts were reviewed, collecting data from the time of diagnosis and initiation of Dara to date of last known follow-up, or death. Progression of disease information and initiation of new therapy was collected during this time frame. Standard methods of survival analysis were used to analyze the primary objectives. Kaplan-Meier estimate was used to analyze PFS and OS at 6, 12, 24, and 36 months. TTNT was defined as length of time from the date of initiation of Dara to the date the patient was started on a new therapeutic regimen. TTP was defined as the date the patient started Dara therapy to the date of documentation of disease progression or relapse. Cumulative incidence rates were calculated to determine the rates of incidence of next treatment in the presence of competing risk of death, and rate of ADEs in patients during this time frame. Rate of ADEs were reported with corresponding 95% confidence intervals using a binomial confidence interval. A total of 50 patients were included in the analysis. Baseline demographics are in line with published data, mean age was 68.8 years, with a non-Caucasian predominance of 68% to 32% Caucasian. The gender profile was 42% male. Prior mean number of therapies was 2.9, with a median of 2. Dose of Dara used was in line with the recommended dosing with mean 16.3mg/kg dosing. The mean number of doses received were 17. Similar to prior published data the predominant heavy chain MM phenotype was IgG at 48%. The OS, at 36 months was 54%, where 23 patients (46%) had documented date of death during the 5-year time span reviewed. Thirty-one patients (62%) experienced disease progression (TTP), ranging from 28 to 1047 days from start of Dara treatment, with a median TTP of 317 days. The median PFS was 436 days (95% CI: 334-676 days). There were 46% patients that continued on another line of therapy post Dara , with the TTNT ranging from 25 to 541 days, median 175 days from initial Dara therapy. Among patients who had at least one adverse event, the most frequently occurring pattern was fatigue, pyrexia, and chills at 22%, followed by infusion related reactions at 20%. Dara has shown strong clinical efficacy clinical trials. The patients in clinical trials are often not reflective of real-world clinical patients. This study evaluates patients at a single cancer center in the NH system. The data reinforces the efficacy and tolerability of Dara in the real-world setting. It also depicts the difference in OS, PFS, TTP, TTNT and ADEs in the real-world setting. The data suggests Dara outcomes in community-based oncology centers vary from clinical trial data. However, it does indicate similar improved benefits in OS, PFS and TTNT compared with other retrospective studies at other centers. Further prospective studies would be beneficial in evaluating this real-world impact. Disclosures No relevant conflicts of interest to declare.

M7-FLIPI is not prognostic in follicular lymphoma patients with first-line rituximab chemo-free therapy.

The clinical course of follicular lymphoma (FL) is highly variable. Recently the m7-FL international prognostic index (FLIPI) integrating performance status, FLIPI score and the mutational status of seven genes, was shown to stratify patients into "low-risk" and "high-risk" with respect to 5-year failure-free survival after first-line immunochemotherapy. Our aim was to evaluate the model after rituximab without chemotherapy. The Nordic Lymphoma Group performed two randomized clinical trials on indolent lymphoma patients receiving single rituximab and rituximab with interferon-α2a. In total, 95 FL patients had sufficient fresh-frozen diagnostic material for sequencing. A targeted panel for the genes EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP and CARD11 was utilized for m7-FLIPI score calculation. With a median follow-up of 10·6years, 76% of patients were alive. No difference in time to treatment failure (TTF), defined as the interval between start of trial therapy and initiation of new therapy or death, nor overall survival (OS) was found between the m7-FLIPI risk groups (log-rank P=0·94 and 0·99, respectively). EZH2 mutations were associated with longer TTF (log-rank P=0·04) and in EP300 mutations were associated with shorter TTF (log-rank P=0·01). We conclude that the prognostic value of the m7-FLIPI clinicogenetic model seems dependent on therapeutic regimen.

Contrast enhancing spots as a new pattern of late onset pseudoprogression in glioma patients.

Magnet resonance imaging (MRI) of gliomas is assessed by Response Assessment in Neuro-Oncology Criteria (RANO), which define new contrast-enhancing lesions as a sign for tumor recurrence. Pseudoprogression after radiotherapy may mimic tumor progression in MRI but is usually limited to the first months after irradiation. We noted a late onset pattern of new contrast-enhancing spots (NCES) appearing years after radiotherapy. We prospectively collected 23 glioma patients with 26 NCES (three patients had two separate NCES events) between 2014 and 2016 in our weekly tumor board without further selection by diagnosis, molecular markers or pretreatment. Retrospective analysis revealed a homogeneous collective of young patients (median age of 49years at NCES) with mainly IDH-mutated glioma (61%). Initial histology showed 26% glioblastoma, 52% grade III and 22% grade II glioma. NCES occurred at late follow-up with a median of 52months after tumor diagnosis and 30months after the last radiotherapy. The majority of NCES regressed spontaneously within a median of 10months (n = 11) or remained stable without further therapy with a median follow-up of 26months (n = 7). Only 4 NCES developed MRI morphologically into tumor recurrence. Two NCES were resected without any histopathological proof of tumor recurrence, and in 2 other cases NCES were defined as ischemic stroke or radionecrosis. We hypothesize that the late onset phenomenon of NCES predominantly represents a form of radiation-induced vasculopathy that is different from early pseudoprogression and should be considered especially in younger patients with IDH-mutated glioma before initiation of new therapy.

Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Commpass Study

Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Commpass Study

Updated combined analysis of two phase II studies of brentuximab vedotin in patients with mycosis fungoides and Sézary syndrome

Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate with activity against mycosis fungoides (MF) and Sézary syndrome (SS). We pooled the updated data of 2 open-label single-arm phase II BV trials in relapsed/refractory MF/SS patients with a spectrum of CD30 expression (0-100% by skin IHC) with the aim to analyze the clinical activity profile in a larger combined cohort. We defined ORR4, ORR6, and ORR12 as objective responses lasting at least 4, 6, 12 months respectively, without initiation of new therapy or PD. MSWAT90 (near CR/CR) was defined as >90% reduction in mSWAT. The two trials had similar study design. Seventy-four patients (MDACC 38, Stanford 36) were included with 92% MF; 14 (19%) stage IB/IIA, 60 (81%) advanced stage (34 IIB, 25 IV); 53% LCT, 42% F-MF; median prior systemic treatments 3. ORR was 57% (42/74) with median time to response of 9 (4–40) weeks. The ORR4 was 49% (36/74), ORR6, 32% (24/74), and ORR12 12% (9/74). Greater improvement in mSWAT was observed in patients with ORR4, ORR6 and ORR12. Although the CR rate was only 5%, the mSWAT90 was 30% (21/74) and was associated with ORR4 and ORR6, p < 0.0001 and p = 0.0001 respectively. While patients with CD30 status at screening >5% had higher ORR, a notable response was still observed in those with <5% expression (63% vs 46%) (p = 0.17). Median time to next systemic treatment (TTNT) of n = 74 was 41 weeks with no significant difference observed by CD30 status >5% vs <5%, p = 0.68. At 1 and 3 years, KM estimates for PFS showed 58% and 23%. The most common related adverse events were peripheral neuropathy 65% (23% G 1, 39% G 2, 3% G 3/4), fatigue 36%, nausea 28%, alopecia 22%, neutropenia 20%, and rash 22%. BV demonstrates high ORR in patients with relapsed/refractory MF/SS with many patients achieving near CR+CR (mSWAT90) in the skin and durable responses. Notable clinical activity was observed in patients with very low CD30 expression levels.

Abstract 1712: Detection of circulating tumor cells in stage IV non-small cell lung cancer

Abstract Non-Small Cell Lung Cancer (NSCLC) is the most common cause of cancer related deaths in both men and women. Some lung cancer patients have a unique challenge of a tissue access due to tumor location or baseline lung disorders such as emphysema and chronic obstructive pulmonary disease (COPD). Liquid biopsy technologies can overcome tissue assess difficulties. However, as of today there are no commercially approved assays for CTC enumeration in lung cancer. Multiple non-commercial assays exist and some show correlation of CTC enumeration and changes in CTC counts on therapy with prognosis and response to therapy. Outside of absolute number of CTC there is little published data regarding prognostic significance of CTC morphologic heterogeneity in late stage NSCLC and its ability to predict treatment outcomes. Here we investigate CTC counts in 81 patients with stage IV NSCLC using a fluid phase biopsy and high definition (HD) diagnostic pathology imaging of all nucleated cells. HD-CTCs were detected in 51 (63%) patients at initiation of therapy with a median of 2.20 (range 0-509.20) and a mean of 26.21 HD-CTCs/mL (±15.64). There was no correlation between the absolute number of HD-CTCs at the time of initiation of new therapy and patient outcomes. A subset of 25 patients was further analyzed to determine the significance of HD-CTC kinetics, which may follow three distinct patterns: an increase in HD-CTCs with therapy, unchanged HD-CTCs numbers (stable), and a decline in HD-CTCs numbers. Patients that experienced an increasing, stable, or decreasing HD-CTC profile had an overall change of 118.40, 0.54, and 81.40 HD-CTCs/mL respectively during the first 3 months. The overall survival (OS) for increasing profiles was 31.08 months (±13.08, median 32.46, range 15.11-43.50), for stable profiles OS was 8.82 months (±3.57, median 7.23, range 3.91-19.75), and for decreasing profiles it was 15.30 months (±6.39, median 14.06, range 3.81-28.06) months. CTCs are identifiable in patients with stage IV NSCLC, but correlation of absolute HD-CTC counts with disease progression was not statistically significant. However, change in CTC counts were predictive of OS in patients with metastatic lung cancer receiving chemotherapy. Citation Format: Stephanie N. Shishido, Lyudmila Bazhenova, Anders Carlsson, James Hicks, Peter Kuhn. Detection of circulating tumor cells in stage IV non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1712. doi:10.1158/1538-7445.AM2017-1712

Phase II Study of Prophylactic Non-Irradiated Granulocyte Transfusions in AML Patients Receiving Induction Chemotherapy

Background: Patients with Acute Myeloid Leukemia (AML) experience profound neutropenia; infections remain the leading cause of morbidity and mortality. Transfusion of functional non-irradiated allogeneic granulocytes may treat or prevent infections in AML patients, and may also have anti-leukemic benefits. Study Design: Patients free of infection, with a diagnosis of AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy were eligible. Allogeneic Granulocyte Transfusions (GTs) were administered to neutropenic (<0.5 × 109/L) patients every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. Results: 45 patients enrolled with a median age of 67 years (range 23-83); 27 (60%) were male. Five patients (11%) never received a GT, due to donor screening failure and/or donor unavailability. 119 donors donated 156 granulocyte concentrates to the remaining 40 patients. The median number of GTs transfused per patient was 3 (range 1-9). All patients experienced >1 neutropenic fever, with an average of one infectious episode per patient. Other adverse reactions were urticaria/pruritis (n=1), rash (n=1), and hypotension (n=1). Response to leukemiadirected therapy included complete remission in 50%, overall response rate of 70%, and 8-week mortality of 8%. Median overall survival was 15 months, with 51% 1-year survival. Conclusion: Administration of non-irradiated functional allogeneic GTs to neutropenic MDS/AML patients is safe and feasible. No transfusion-associated graft-versus-host-disease (TA-GVHD) was reported and no increased toxicity was described, including among the 10% receiving subsequent allogeneic stem cell transplant. The favorable patient outcomes within this diverse group of primarily elderly AML are notable.

Final Results of a Phase 2 Study of Bendamustine in Combination with Dexamethasone in Patients with Previously Treated Systemic Light-Chain (AL) Amyloidosis

Background: No established therapies exist for patients who fail or relapse after initial therapy for AL amyloidosis. Bendamustine has shown potential in treating multiple myeloma, chronic lymphocytic leukemia and non-Hodgkins lymphoma but it has not been well studied in AL amyloidosis. We sought to investigate the efficacy and safety of using Bendamustine in combination with dexamethasone (Ben/Dex) in patients with relapsed AL amyloidosis in a multi-center phase 2 study and present the results of the final analysis.Methods: This Phase IIa clinical trial enrolled 31 patients who had persistent or progressive AL amyloidosis after at least 1 prior therapy. An optimal two-stage Simon design approach was used. Of 13 patients initially enrolled, 3 experienced hematologic partial response (PR), and an additional 16 were treated in the second stage. It was pre-determined that if 9 or more of the 29 patients with evaluable response had hematologic PR or better the treatment would be considered worthy of further development. Evaluable response was defined as patients who completed at least 2 treatment cycles. The primary objective was to determine the rate of partial hematologic response (PR). Secondary objectives included the overall hematologic response rate, organ response rate, toxicity profile, event free survival, and overall survival (OS). Patients received treatment in 28 day cycles with Bendamustine given on day 1 and day 2 (100 mg/m2 IV for CrCl≥60 mL/min, 90 mg/m2 IV for CrCl 59-30 mL/min, 70 mg/m2 IV for CrCl 15-30 mL/min) and dexamethasone 20-40 mg given weekly. Treatment was continued until disease progression or for up to 6 courses after complete response (CR). Reasons for discontinuation also included unacceptable toxicity, patient refusal, and non-response.Results:Of the 31 patients enrolled in the trial, 29 had evaluable responses and completed a median of 4 cycles of therapy (range 2-12) with one patient still undergoing treatment as of 7/1/2016. Median age of enrolled patients was 64 (range 42-78). Primarily involved organs included heart (53%), kidney (36%), nerve (7%), and liver (4%); 18 patients had ≥2 major organs involved. The patients received a median of 1.5 prior treatments (range 1-4) and 13 had received prior autologous stem cell transplants. Of evaluable patients (n=29), 41% had hematologic response to Ben/Dex (3% CR, 17% very good partial response, 24% PR). Of these 13 patients, 6 had a response after only 1 cycle of therapy and the median time to best response was 1 cycle (range 1-6 cycles). The median follow up of patients was relatively long, 18.4 months (range 1.5-41.5) and the median OS has not yet been reached (Figure 1). Event free survival defined as time to death, progression of disease or initiation of new therapy was 9.24 months (range 1.8-18.0) (Figure 2). Only 3 patients discontinued treatment due to disease progression while 8 stopped due to an adverse event (AE) although 5 AEs were only grade 1-2 events. There was 1 death during treatment that was unrelated to the study drug and due to underlying cardiac amyloidosis. The most common drug related all grade AEs included anemia (9%), fatigue (8%), and nausea (7%). Organ response was observed in 5 out of 16 patients with renal involvement and 2 out of the 19 patients with cardiac involvement.Conclusions: Bendamustine in combination with dexamethasone is active treatment in patients with AL amyloidosis who had failed multiple prior therapies and results in a significant hematologic response. Treatment was very well tolerated with a low incidence of severe AE in this delicate patient population. Therefore bendamustine is another treatment approach for AL amyloidosis patients who currently have limited therapeutic options. [Display omitted] [Display omitted] DisclosuresLentzsch:Foundation One: Consultancy; BMS: Consultancy; Celgene: Consultancy, Honoraria. Comenzo:Karyopharm: Research Funding; Prothena: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Zonder:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Pregja:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pharmacyclics: Other: data safety monitoring committee. Landau:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy.

Abstract P6-01-02: Flourine-18-fluorodeoxyglucose positron emission tomography for the evaluation of response to therapy in bone-dominant metastatic breast cancer: Examination in patients enrolled on UPCC 17113

Abstract Background: Response of bone-only (BO) and bone-dominant (BD) metastatic breast cancer (mBC) to therapy is difficult to assess by conventional imaging. UPCC 17113 is a single institution prospective cohort study evaluating FDG PET at early and conventional follow up intervals, 4 and 12 weeks respectively, in patients with hormone receptor (HR) positive mBC receiving endocrine therapy. The objective of this study is to assess the relationship between changes relative to baseline in standard uptake values (SUV) of specific bone lesions and progression free survival (PFS). We will also explore change in SUV as it relates to overall survival (OS) and skeletal related events (SRE). We present interim results. Methods: Enrolled patients were ≥18 years with biopsy proven or documented clinically obvious HR-positive BD/BO mBC due to start new endocrine therapy. Any line endocrine therapy was allowed. FDG PET was performed at baseline, 4 and 12 weeks after initiation of new therapy. SUVmax for the 5 most metabolically active osseous lesions, excluding sites previously treated by radiation or surgery, were recorded at baseline, 4- and 12- week time-points. Average index lesion SUVmax (sum SUVmax/#lesions) and % change from baseline were calculated. Decline of ≥30% from baseline was defined as significant. Results: As of 6/1/2015, 11 patients were enrolled. All patients have completed the 4-week scan and 8 have completed the 12-week scan. Five and 6 out of the 11 patients had BO and BD HR-positive mBC respectively. Detectable changes in SUV from baseline were noted in all patients at both 4 and 12 weeks, with a 37% overall decline in average index lesion SUVmax at 4 weeks. 8 of 11 patients had a ≥30% decline, in SUV at 4 weeks averaging 46%. Five of the 6 patients in this group who completed the 12-week scan had a sustained decline averaging 50% from the baseline. Of note, the average decline between 4 and 12 weeks in this group was only 8%. Despite having an overall decline from baseline of 44%, the sixth patient in this group had an increase between 4 and 12 weeks of 22%. Three of the 11 patients had a &amp;lt;30% decline at 4 weeks with an average decline of 12%. Of the two patients in this group with 12 week scans, both had average increase of 25% from 4 weeks to 12 weeks, and an average overall increase from baseline of 12%. Conclusions: There are detectable changes in FDG SUV of osseous lesions at 4 and 12 weeks following initiation of endocrine therapy in patients with BO or BD HR positive mBC. Our interim results demonstrate the emergence of 3 groups of patients: (1) those who have a &amp;lt;30% decline at 4 weeks and increase of SUV at 12 weeks, (2) those who have a ≥30% decline in SUV at 4 weeks with sustained decline at 12 weeks, and (3) those who have a ≥30% reduction in SUV at 4 weeks but who do not have a sustained decline at 12 weeks. These interim results suggest that early FDG PET/CT may provide information on mBC response to endocrine therapy and insight into timing of response and progression. As more patients are enrolled and complete the studies, clearer patterns will emerge which will be correlated with PFS, OS and SRE. Citation Format: Lynch MC, Mankoff D, Bradbury AR, Domchek S, Glick JH, Matro J, DeMichele A, Clark AS. Flourine-18-fluorodeoxyglucose positron emission tomography for the evaluation of response to therapy in bone-dominant metastatic breast cancer: Examination in patients enrolled on UPCC 17113. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-01-02.

Development and validation of a recurrent Clostridium difficile risk‐prediction model

Recurrent Clostridium difficile infection (rCDI) affects 10% to 25% of patients with initial CDI (iCDI). Initiation of new therapies that reduce recurrences rests on identifying patients at high risk for rCDI at iCDI onset. To develop a predictive model for rCDI based on factors present at iCDI onset. Retrospective cohort study. Large urban academic medical center. All adult patients with an inpatient iCDI from January 1, 2003 to December 31, 2009. None. Positive toxin assay for C difficile with no C difficile infection in the previous 60 days constituted iCDI. Repeat positive toxin within 42 days of stopping iCDI treatment defined rCDI. Three demographic, 13 chronic, and 12 acute disease characteristics, and 7 processes of care prior to or at the onset of iCDI, were assessed for association with rCDI. A logistic regression model to identify predictors for rCDI was developed and cross-validated. Among the 4196 patients enrolled, 425 (10.1%) developed rCDI. Six factors (case status as community-onset healthcare-associated, ≥2 hospitalizations in the prior 60 days, new gastric acid suppression, fluoroquinolone and high-risk antibiotic use at the onset of iCDI, age) predicted rCDI in multivariate analyses, whereas intensive care unit stay appeared protective. The model achieved moderate discrimination (C statistic 0.643) and calibration (Brier score 0.089). Its negative predictive value was 90% or higher across a wide range of risk. Among patients hospitalized with rCDI, multiple factors present at the onset of iCDI increased the risk for rCDI. Recognizing patients at high-risk for rCDI can help clinicians tailor early treatment and prevention.

Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer

We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥ 10 ng/ml and CEA measurements within ± 30 days of the CTC collection were included. We included 217 patients with mCRC who had a CEA value of ≥ 10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥ 25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥ 3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.

Rituximab (R) in Combination with Interferon-a2a (IFN) Versus Single R in Patients with Follicular or Other CD20+ Low-Grade (indolent) Lymphoma. Final Results From a Randomized Phase III Study From the Nordic Lymphoma Group

AbstractAbstract ▪794▪This icon denotes a clinically relevant abstract Introduction/Purpose:The optimal treatment schedule and best order of therapies are not well established for patients (pts) with indolent lymphoma. The aim of this trial was to evaluate the effect of adding interferon-alpha (IFN) to first-line rituximab (R) monotherapy, with extended dosing, in pts with CD20+indolent lymphoma and to define pts with no need of initial chemotherapy. Patients and methods:Pts with symptomatic, advanced indolent lymphoma (previously untreated or at first relapse after a short course of chlorambucil) were randomized to R (MabtheraR) 375 mg/m2 once-weekly for 4 consecutive weeks or R with 5 weeks IFN (Roferon-AR) as priming. Patients achieving either a complete response (CR), partial response (PR) or a minor response (MR) at evaluation 6 weeks after last R in this first cycle, were planned to receive a second cycle with four infusions of R alone or combined with IFN, according to the initial randomization. Primary endpoint was time to treatment failure (TTF), defined as the time period from randomization to one of the following events: progressive disease during treatment, death of any cause or initiation of new therapy. Results:In total, 313 patients were randomized. The median age was 59 years, 51% were females, 90% Ann Arbor stage III or IV and 31% showed elevated LDH. The clinical characteristics were well-balanced between the treatment groups. Pathology review showed 127 follicular lymphoma (FL) grade I, 110 grade II and 9 grade IIIA. In total, 4 pts in each arm did not fulfill inclusion criteria: 5 DLBCL/ transformed, 2 MCL and one Hodgkin. Most patients were previously untreated, but 10 pts in the R group and 13 with R+IFN had had a previous response to chlorambucil and 18 and 9 had had local radiotherapy. respectively. After cycle 1, response rates among all 313 randomized pts were 8.6 % CR/CRu, 47.9 % PR, 22.4 % MR and 16.9 % of pts were considered resistant (SD/PD). In total 244 pts were qualified for cycle 2. Overall response rates after cycle 2 were 82% and 74%, in the R+IFN- and the R-group, respectively (n.s), but the CR/CRu rates were higher with the combination (41% vs 22.4%, p< 0.01). Also pts with FLIPI 3–5 (45% of all pts) showed a deeper response with R+IFN (CR/Cru 38.0% compared to 23.1%). More patients in the combination arm improved their responses from PR/MR in cycle 1, to CR after cycle 2. In the intention–to treat (ITT) population (n=313), median time to TTF was 21 and 28 months in the R and R+IFN group, respectively. Most events consisted of initiation of new therapy including chlorambucil, COP or CHOP, but in 7 patients in the R group, relapse treatment was single R (in one case with the addition of IFN) and in the R+IFN group 10 pts had R (3 with IFN). Two pts in the R-group and 12 pts in the R+IFN group had late relapses treated with local irradiation. After a median follow-up time of 60.7 months, for surviving pts, 35 % of the ITT patients were still event-free with 90% survivors, but with no difference between the treatment groups. Patients with FL grade II and IIIA showed a longer TTF than pts with grade I (p=0,05). Conclusion:This randomized phase III trial demonstrates that extended rituximab therapy is safe and effective as first-line therapy in patients with symptomatic low-grade B-cell lymphoma, with improved responses and a delayed time to early failure if combined with IFN. The long term FU suggests that more than 1/3 of this patient population does not need initial chemotherapy, but predictive markers for response to R and new biological combinations are needed. Disclosures:Kimby:Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees.

An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy In Patients with Stage II, III, IV, Asymptomatic, Non-Bulky Follicular Lymphoma (Grades 1, 2 and 3a). A Preliminary Analysis

Abstract 6 Patients with asymptomatic, advanced stage, follicular lymphoma have shown no benefit of immediate chemotherapy when compared with a watchful-waiting approach, whereby chemotherapy is deferred until disease progression. Deferring chemotherapy may spare the patient the side effects of the chemotherapy in the short term and historically this has been the preferred approach. With the advent of rituximab and its relatively favourable side effect profile we designed this study to compare a watchful waiting approach with immediate treatment with rituximab. Adult patients with asymptomatic stage 2, 3 or 4 follicular lymphoma (grades 1–2 & 3a) and adequate bone marrow reserve were randomly assigned with a ratio 1:1:1 to watchful waiting (arm A) or rituximab 375mg/m2 weekly for 4 weeks (arm B) or rituximab 375mg/m2 weekly for 4 weeks followed by rituximab maintenance every 2 months for 2 years (starting at month 3 until month 25)(arm C). The primary endpoints were a) time to initiation of new therapy (chemotherapy or radiotherapy) and b) effect on quality of life. The study was designed to detect an improvement in the median time to initiation of therapy in each of the rituximab arms of 18 months (from 30 months to 48 months) with 2.5% significance level and 90% power. A total of 230 events were required and 600 patients were planned. In September 2007, a decision was made to discontinue arm B as evidence of the efficacy of maintenance rituximab became clear. With the two arms comparison, using a significance level of 5%, a total of 360 patients in Arm A and Arm C were planned. Between September 2004 and May 2009 462 patients were randomised (186 Arm A, 84 Arm B, and 192 Arm C). 95% of patients had low tumour burden (GELF criteria) the other 5% had raised LDH but fulfilled the remaining GELF criteria. 98% were entered into the study within 4 months of diagnostic biopsy. Median age 60yr (range27-87). 54% female. ECOG performance status 0=91% & 1=9%. Grade 1–2=89%. Stage 2(21%), stage 3(40%), stage 4 (39%). 42% had bone marrow involvement. FLIPI score: 0=9%, 1=26%, 2=41%, 3=22%, 4=2%. In March 2010 the Data Monitoring committee concluded that the data regarding time to initiation of new therapy was mature and recommended full analysis of data to be performed and presented in the knowledge that rituximab maintenance was still ongoing in 20 patients. To date 45 SAEs have been reported (Arms A=14, B=6, C=25), 14 SAE were considered possibly, probably or definitely related to the study drug (Arm B=4, C=10). 5 allergic reactions (two grade 3), 6 infections, 3 episodes of grade 4 neutropenia. Responses were assessed at month 7, 13 and 25. CT was compulsory at months 7 and 25. Bone marrow was only required if CR on clinical and CT criteria. An interim analysis was performed on 9 Feb 2010. At month 7: Arm A: spontaneous remission was seen in 3%, PR=6%, NC (no change) =74%, PD=17%. Arm B: CR+CRu=45%, PR=33%, NC=19%, PD=3%. Arm C: CR+CRu=49%, PR=36%, NC=11%, PD=3%. At the time of the interim analysis 93 (20%) patients had initiated new treatment. Of these 93 patients 84 (90%) had clinically reported progression. New treatment was chemotherapy in 78 (84%), radiotherapy in 10 (11%), rituximab monotherapy in 2 (2%), surgery in 1(1%),currently not known in 2 (2%). The estimated median time to initiation of new therapy in arm A was 33 months, similar to our previous trial of watchful waiting (Ardeshna et al Lancet 2003). The time to initiation of new therapy was significantly longer in the rituximab arms (fig 1, p value of log-rank test 0.5). These data indicate that initial treatment with rituximab significantly delays the need for new therapy and this finding may change the management of patients with newly diagnosed asymptomatic follicular lymphoma. Disclosures: Ardeshna:Roche: Funding data manager, Honoraria, Membership on an entity9s Board of Directors or advisory committees. Off Label Use: Rituximab is currently not licensed for use as a single agent in previously untreated patients with with asymptomatic advanced stage follicular lymphoma. Pocock:Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Cunningham:Roche: Research Funding. Davies:Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees; chugai: Honoraria, Research Funding. Walewski:Roche: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Linch:Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees.