Rates Of Neutropenia Research Articles

POS0655 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: 3-YEAR RESULTS FROM THE SELECT-EARLY STUDY

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy (mono) vs methotrexate (MTX) in MTX-naïve patients (pts) with rheumatoid arthritis (RA) through 48 weeks (wks).1Objectives:To report the efficacy and safety of UPA vs MTX mono up to 156 wks in pts with RA from the ongoing long-term extension (LTE) of the SELECT-EARLY trial.Methods:During the 48-wk double-blind study period, pts were randomized to UPA 15 or 30 mg once daily (QD) or MTX (titrated to 20 mg/wk by Wk 8). At Wk 26, pts who did not achieve Clinical Disease Activity Index (CDAI) remission (≤2.8) and had <20% improvement from baseline in tender or swollen joint count received blinded rescue therapy (addition of MTX for UPA groups and UPA 15 or 30 mg for MTX group). In the LTE, pts received open-label treatment once the last pt reached Wk 48. Efficacy assessments up to Wk 156 were summarized by randomized group and included American College of Rheumatology (ACR) responses, remission and low disease activity (LDA) measures, and change in modified Total Sharp Score (mTSS; up to 96 wks). Treatment-emergent adverse events (AEs) per 100 pt-years (PY) for pts on continuous mono were summarized through 156 wks. Non-responder imputation was used for binary endpoints for missing data and when pts received rescue therapy or prematurely discontinued the study drug.Results:Of 945 pts randomized and treated, 775 entered the LTE on study drug (including 57 rescued pts; MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). Overall, 161 (21%) pts discontinued during the LTE. At Wk 156, higher proportions of pts randomized to UPA achieved a 20/50/70% improvement in ACR response (ACR20/50/70), LDA, and remission vs MTX (Figure 1). Change from baseline in mTSS at Wk 96 favored UPA vs MTX (data not shown). Most AEs were numerically more frequent with UPA 30 mg. The overall rate of serious infection was numerically higher with UPA vs MTX (Table 1). Herpes zoster (HZ), neutropenia, non-melanoma skin cancer (NMSC), and creatine phosphokinase (CPK) elevation were more frequent with UPA vs MTX. Two active tuberculosis (TB) events were reported in each UPA arm; 3 adjudicated gastrointestinal (GI) perforation events were observed in the UPA 30 mg arm. Adjudicated major adverse cardiovascular events (MACEs) or venous thromboembolic events (VTEs) were comparable across treatment arms.Conclusion:UPA monotherapy showed sustained clinically meaningful responses including remission vs MTX through Wk 156 but higher rates of several AEs, including HZ, neutropenia, and CPK elevations; no new safety risks were observed compared with previous results.1,2

CONCURRENT CHEMO-RADIOTHERAPY OF WEEKLY PACLITAXEL VERSUS WEEKLY CARBOPLATIN IN LOCALLY ADVANCED HEAD AND NECK CARCINOMAS UNFIT FOR CISPLATIN

Background: Chemoradiotherapy have an important role in the treatment of locally advanced head and neck cancers, in old age patients with, renal and cardiac dysfunction ineligible for cisplatin, We compared weekly Taxol versus weekly carboplatin .AIM: Our study aiming to comparing the efficacy and toxicities of chemo radiotherapy of weekly Taxol versus weekly carboplatin in locally advanced head and neck carcinoma. PATIENT AND METHODS: The study divided in two arms, paclitaxel arm; 25patients treated by weekly paclitaxel 40mg/m2 with radiotherapy and carboplatin arm; 25 patients treated by weekly 150mg carboplatin with radiotherapy. The three-dimensional radiotherapy planned (3DCRT) was 65 to 70 GY and 1.8 -2 GY /fraction, 5 fractions/week in 6-7 weeks. RESULTS: There was an insignificant 5-year disease free survival was 79.5% in carboplatin arm versus 84.6% in paclitaxel arm and 5-year OS was an insignificant 76% in carboplatin arm versus 72% in paclitaxel arm (p-value=0.646) . A 44% of both arms had overall complete remission. A 16% of patients received carboplatin had grade III/IV mucositis. Patients in paclitaxel arm had more grade II neuropathy (60%). A comparable rate of neutropenia had occurred in both arms. CONCLUSION: Both arms of concurrent chemo radiotherapy had acceptable toxicities with good quality of life response to treatment where 44% of both arms had complete response (p-value=0.623). There was an insignificant 5-year disease free survival was 79.5% in carboplatin arm versus 84.6% in paclitaxel arm and 5-year OS was an insignificant 76% in carboplatin arm versus 72% in paclitaxel arm (p-value=0.646).

Side effects of CDK4/6 inhibitors in the treatment of HR+/HER2- advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Although combination of cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors with endocrine therapy for advanced breast cancer (ABC) prolongs PFS in patients, but also has associated toxic side effects. However, few previous studies have summarized the toxic and side effects of CDK4/6 inhibitors. Therefore, this study summarized the corresponding toxic and side effects of CDK/6 inhibitors, which is of great importance for doctors and patients to understand how to balance the high survival rate brought by drugs with the decreased quality of life and improve the management of BC. PubMed, Embase, The Cochrane Library, and VIP databases were systematically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from January 2010 to December 2019.Two investigators independently reviewed the literatures. Before using the RevMan 5.3 software for a meta-analysis, date were extracted and the risk of bias with the include studies were assessed. A total of 64 RCTs involving 3685 patients were included. Compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (hazard ratio 0.54, 95% confidence interval (CI):0.50-0.60, P<0.00001). In terms of adverse reactions, CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased alanine aminotransferase (ALT). CDK4/6 inhibitors have strong specification in the treatment of ABC because of their role in regulating the cell cycle. Although CDK4/6I combined with endocrine therapy can improve the effective rate and median PFS of patients with HR+/HER2-ABC, this treatment regimen increases the incidence of adverse reactions such as neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased ALT. Further research into improving the survival rate while reducing or even avoiding the side effects of CDK4/6Isis needed for better clinical management of BC. PROSPERO (CRD42020171112).

Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials

BackgroundIn the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy.MethodsAll eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events.ResultsData of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001).ConclusionAlthough the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.

A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401.

Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis. Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04). Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm. ClinicalTrials.gov Identifier Registry number: UMIN000013133.

Abstract PS15-09: Adverse events in breast cancer patients treated with concurrent or sequential radiation therapy and CDK 4/6 inhibitors in metastatic setting

Abstract Background. Radiation therapy (RT) is important modality in MBC patients, however, there is paucity of data on safety and feasibility in combining radiation and a cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6i). No sufficient data were gathered in clinical trials and a few small retrospective series were published; it is important to extend these data. Theoretically, concerns pertain both the augmentation of effect (toxicity) or decrease of treatment effectiveness. Methods. 116 patients with MBC were treated in our center with CDK 4/6i (ribociclib n=59, palbociclib n=57) between 2018-2020. 26 patients were also treated with RT and were included into further analysis. 10 patients were treated with concurrent RT and 16 patients with sequential RT. Median age of patients was 55 years (range 23-78). 11 patients (42%) were diagnosed with de novo MBC, whereas 15 patients (57%) with recurrent breast cancer. 16 patients received prior chemotherapy, 6 of them less than 1 year before CDK 4/6i treatment. 73% of patients received CDK 4/6i in first line setting. Bones were the main metastatic site in the majority of patients, whereas visceral metastasis were diagnosed in 9 patients (35%). Overall 32 RT treatments in 26 patients were performed. Various RT regimens were used, including 8 Gy in 1 fraction (n=10), 20 Gy in 5 fractions (n=9), 30 Gy in 10 fractions (n=3). SBRT was performed in 5 patients and chest wall irradiation in 3 patients. The majority of patients received palliative radiotherapy to the bones, including 6 patients (23%) with RT to the pelvic area. Results. Nineteen patients (73%) experienced G2 and G3 neutropenia, with no G4 case. Neutropenia G≥2 occurred during first cycle of CDK 4/6i treatment in 50% of patients (n=8) after sequential RT and signicantly more often in patients after concurrent RT (all treated, n=10; p= 0.0095). No neutropenia was observed in 7 patients after sequential RT (27%). 4 patients (15%) had CDK 4/6i dose reduction, including 1 patient treated with concurrent RT and 3 patients treated with sequential RT. In all 4 patients the cause of dose reduction was prolonged G3 neutropenia. Patients were treated as follows: 60yo patient received RT 8 Gy in 1 fraction for bone metastases in lumbar and thoracic spine and ribs; 31yo patient received RT 20 Gy in 5 fractions for central nervous system, then 20 Gy in 5 fractions for bone metastases in thoracic, lumbar and sacral spine (all of these treatments were performed during 4 weeks before CDK 4/6i first dose). The following two patients received additionally doxorubicin-based chemotherapy shortly before CDK 4/6i treatment. At median follow up of 17 months (range 9-20 months) none of these patients discontinued treatment because of toxicity: one patient continue ribociclib at first dose reduction level, two patients continue ribociclib at second dose reduction level and one patient continued ribociclib treatment for 11 consecutive months and then CDK 4/6i treatment was ended because of disease progression. There was no difference in neutropenia rate in patients treated previously with chemotherapy (n=16) and chemo-naïve patients (n=10; p=0.6680). No cases of acute radiation-induced enterocolitis or enhanced dermatologic toxicity were found. No other serious adverse events were observed. Conclusions. We found that concurrent RT leads to more frequent neutropenia than sequential RT, although it did not change treatment course in the majority of patients and appeared well-tolerated. Potential risk factors for radiation-induced CDK4/6i dose reduction might be extensive radiation fields and previous chemotherapy in metastatic setting. Until now, combined RT is not a part of adjuvant CDK 4/6i clinical trials protocols. Excellent tolerance of this combination supports future consideration of this scenario in clinical trial setting. Citation Format: Marcin Kubeczko, Agnieszka Badora-Rybicka, Anna Polakiewicz-Gilowska, Aleksandra Leśniak, Katarzyna Świderska, Marta Mianowska-Malec, Barbara Grandys, Barbara Łanoszka, Magdalena Stankiewicz, Marzena Gawkowska, Elżbieta Nowicka, Grzegorz Woźniak, Dorota Gabryś, Rafał Tarnawski, Leszek Miszczyk, Michał Jarząb. Adverse events in breast cancer patients treated with concurrent or sequential radiation therapy and CDK 4/6 inhibitors in metastatic setting [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-09.

Abstract PS10-25: Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study

Abstract IntroductionThe management of metastatic oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer has evolved with the introduction of CDK4/6 inhibitors improving disease outcomes when added to an AI in the first line setting. The FDA evaluated toxicity of all CDK4/6 inhibitors in women ≥75 years (n=198), and found increased toxicity and dose modifications [1], however, toxicity profiles differ between the CDK4/6 inhibitors. Palbociclib has been shown to be well tolerated in patients ≥75 years (n=83) [2] and ≥ 70 years (n=92) [3], however, more real-world data is essential to inform prescribing practices in larger datasets.MethodsWe undertook a national multi-centre retrospective study with 15 cancer centres participating. All patients aged ≥75 years with ER+/HER2- advanced breast cancer who had received at least 1 cycle of Palbociclib + AI as part of a patient access scheme or NICE approved by 1st December 2019 were included. Data collected included baseline characteristics, comorbidities, disease characteristics, toxicities with palbociclib, dose modifications, dose delays, discontinuation and response to treatment.ResultsData from 123 patients aged ≥75 years are included in this analysis from 3 UK cancer centres. Median age was 79 years (range 75 - 90). 98% had an ECOG performance status of 0-2. Co-morbidities were scored using Charlston comorbidity index (CCI - higher score signifies more co-morbidities). 102 patients had a CCI of ≤10 and 18 had a CCI &amp;gt;10. The starting dose of palbociclib was 125mg in 115 patients, but 8 (6.5%) patients started at a lower dose, a third of whom had a CCI of &amp;gt;10. The average number of concurrent medications was 4 (range 0-12). Visceral metastases were present in 52% of patients, and 33 patients (26.8%) had bone only metastases. The median number of cycles received was 10 (range 1 -36). 60 (48.8%) patients required one dose reduction, 18 patients required a 2nd dose reduction and 2 patients required a 3rd dose reduction. The most common cause for dose reductions was neutropenia G3-4 (n=31) and fatigue G1-3 (n=12). 75 patients (61%) required a dose delay and 9% of patients discontinued treatment due to toxicity. The rate of all grade neutropenia was 88.6% with only 1 patient (0.8%) developing febrile neutropenia. Other all grade common toxicities were fatigue (62.6%), anaemia (61.8%) and thrombocytopaenia (57.7%). 12 (9.7%) patients required hospital admission due to side effects of treatment. At the time of data analysis, 111 patients had had a radiological response assessment and the best response was stable disease in 57.7%, partial response in 32.4% and complete response in 0.9% (1 patient) with a clinical benefit rate (CR+PR+SD ≥24 weeks) of 83.8%. 10 patients (9%) had disease progression. The median progression free survival is immature, but at the time of this analysis was 13 months (range 1-36 months).ConclusionOur real world data contributes to the existing smaller published datasets in the over 75s to reassure clinicians that palbociclib is an effective and manageable treatment choice in older women. Compared to published data in older patients [2, 3], febrile neutropenia rates from palbociclib were lower. Despite a higher dose reduction and delay rate than published data [3], the clinical benefit rate was not adversely affected and the early PFS signal is reassuring. Citation Format: Salma El Badri, Daniel Hills, Alicja Synowiec, Catherine Harper-Wynne, Maung Moe, Caroline Wilson. Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-25.

Abstract PS12-25: Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy

Abstract Background: Advancement in the treatment of metastatic estrogen receptor positive (ER+) breast cancer has led to the introduction of CDK4/6 inhibitors such as Palbociclib, which are associated with reversal of endocrine resistance and delayed requirement for chemotherapy. Clinical trials to date have demonstrated improved survival outcomes for patients on these agents. The objective of this study was to evaluate their role in a real-world setting. Methods: We performed a retrospective multicentre analysis of patients (pts) with metastatic ER+ breast cancer who were commenced on Palbociclib (PAL) between January 2010 and September 2019. Data extracted included demographics, disease characteristics, treatments, toxicities, response rates and survival outcomes. Statistical analysis was performed using Cox proportional hazard model for univariate analysis and Kaplan Meier curves for survival data. Results: We identified 271 pts. The median age was 60 years (31-88) and 18% (n=48) pts were premenopausal. PAL was combined with the following ET partners: Aromatase inhibitor (AI) (38%, n=103), Fulvestrant (FUL) (38%; n=103), Tamoxifen (4%, n=10), FUL &amp; AI combination (16%, n=44) and other (4%, n=11). Among 71 pts treated in the 1st line, overall response rate (ORR) was 56% (n=40). The median PFS (progression free survival) was 35 months (95% confidence interval [CI], 17.2-52.7) in all pts and 25 months (mo) in those not treated with FUL. In 1st line pts with de novo disease (37%, n=26), there appeared to be a trend towards improved PFS in the FUL vs non FUL group - not reached vs 25 mo (HR 0.21; 95% CI 0.02-1.79, p=0.15). There was no significant difference in PFS between the FUL vs non FUL group in relapsed pts (63%, n=45) treated in the 1st line - 22 vs 20 mo (HR 1.0, 95%CI 0.35-2.9; p=0.96). The median OS was 59 mo (95% CI, 9.5 to 108). Of 74 pts treated in the 2nd line, ORR was 24% (n=18), median PFS was 10 mo (95% CI, 5.8-14.1) &amp; OS was 25 mo (95% CI, 18.3-31.6). Among 126 3rd line pts, ORR was 16% (n=20), median PFS was 5 mo (95% CI, 3.5-6.4) and OS was 20 mo (95% CI, 12.8-27.1). 3 of 9 pts achieved &amp;gt;6 mo of stable disease after switching ET and continuing Palbociclib beyond progression. The most frequent grade 3 toxicities were neutropenia (40%), anaemia (4%), fatigue (3%) &amp; thrombocytopenia (2.5%). The rate of febrile neutropenia was 2.5%. Dose reductions occurred in 40%, with the most common reason being neutropenia. Treatment was discontinued in 3% due to toxicity. Premenopausal status or dose reductions were not associated with poorer survival outcomes. Conclusions: Palbociclib appears to be safe and tolerable in a real-world population and is associated with favourable survival outcomes comparable to that seen in a clinical trial setting. Combining Palbociclib with Fulvestrant as opposed to other endocrine therapies may delay progression in the 1st line setting in patients with de novo metastatic ER+ breast cancer but larger studies are needed to explore this hypothesis further. Citation Format: Lisa Prior, Darko Skrobo, Hazel Murray, Abdul Rehman Farooq, Anne Horgan, Paula Calvert, Emmet Jordan, John McCaffrey, Lillian Smyth, Miriam O'Connor, Michaela Higgins, Desmond Carney, Janice Walshe, Giuseppe Gullo, John Crown, Catherine M Kelly. Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-25.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

Twenty Years of Radiation Therapy of Unresectable Intrahepatic Cholangiocarinoma: Internal or External? A Systematic Review and Meta-Analysis

Purpose: Both external beam radiation therapy (EBRT) and selective-internal radiation therapy (SIRT) are implemented to treat unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to evaluate the efficacy of EBRT and SIRT in managing iCCA through a systematic review and meta-analysis. Methods: PubMed and Cochrane database were queried to search for studies published from January 2000 toJune 2020 without language restrictions. Median survival time, overall survival, and radiological response were extracted. Secondary outcomes such as complication rates, predictors of survival, and downstage to surgery were pooled. Patient-level survival data were obtained to generate Kaplan-Meier survival graph. Pooled outcomes were analyzed with a random-effect model. Results: Twenty-nine and 20 studies including 732 and 443 patients from the SIRT and EBRT groups were included in the present study. From initial radiation treatment, the median survival time for patients who underwent SIRT and EBRT were 12.0 (95% confidence interval [CI]: 10.8–14.6) and 13.6 (95% CI: 11.1–16.0) months, respectively. As first-line therapy, the median survival time was 36.1 (95% CI: 20.6–39.5) months for SIRT and 11.0 (95% CI: 9.3–13.6) months for EBRT. Both radiation modalities were effective in downstaging initially unresectable iCCA to surgery (SIRT: 30.5%; EBRT: 18.3%). Patients in the SIRT group encountered more post-embolization abdominal pain (6.9 vs. 2.2%), ulcer (1.0 vs. 0.5%), nausea (1.6 vs. 0.7%), anorexia (5.9 vs. 0%), thrombocytopenia (7.3 vs. 6.0%), hyperbilirubinemia (5.2 vs. 2.1%), and hypoalbuminemia (13.2 vs. 3.3%), whereas EBRT was associated with higher rates of anemia (0.6 vs. 7.5%) and neutropenia (6.5 vs. 11.0%). Conclusions: Both EBRT and SIRT were safe and effective in treating unresectable iCCA. However, available evidence was highly heterogeneous regarding patient population, limiting fair comparison between 2 radiation modalities. Future high-quality comparative studies are warranted.

Carboplatin in combination with 3-weekly paclitaxel as first-line therapy in patients with recurrent/metastatic head-and-neck cancers: A regional cancer center experience

Background: Head-and-neck cancers (HNCs) collectively are the sixth most common malignancy diagnosed worldwide and treatment in recurrent/metastatic setting is challenging. This retrospective study aimed to evaluate the efficacy and tolerability of carboplatin and paclitaxel as first-line treatment in patients with recurrent and/or metastatic (R/M HNCs). Materials and Methods: A total of 182 patients with recurrent and/or metastatic HNC who received carboplatin and paclitaxel combination 3 weekly as first-line therapy at medical oncology department of our tertiary care cancer institute in Bangalore between January 2018 and January 2020 were reviewed. The patients who progressed during chemotherapy were receiving oral metronomic chemotherapy or best supportive chemotherapy. The patients were followed up every 2 monthly. Results: At the completion of treatment, the overall response rate was 15.4%. The median progression-free survival was 4.3 months (95% confidence interval [CI]: 2.9–5.6), and the median overall survival was 8.2 months (95% CI: 6.8–9.7). The main toxicities in the present study were Grade 3–4 hematologic 19.8%, mucositis 1.6%, and diarrhea 2.7%, and the rate of febrile neutropenia was 6.6%. None of the patients died of treatment-related toxicity. Conclusion: The combination of carboplatin with 3-weekly paclitaxel is effective in R/M HNC patients.

Randomized Trial With or Without Granulocyte Colony-Stimulating Factor as Adjunct to Induction VNCOP-B Treatment of Elderly High-Grade Non-Hodgkin's Lymphoma

AbstractAge is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF ) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 μg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve.

STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features.

Simple SummarySTAT3 and STAT5B mutations have been identified in a subset of T and NK large granular lymphocytic leukemia (T/NK-LGLL). The aim of our study was to evaluate the frequency and type of these mutations in all different subtypes of T/NK-LGL expansions (n = 100 patients), as well as to analyze its association with biological and clinical features of the disease. We show for the first time that STAT3/5B mutations were present in all different T/NK-cell LGLL categories here studied; further, STAT3 mutations were associated with overall reduced counts of almost all normal residual populations of immune cells in blood, together with a shorter time-to-therapy vs. wild type T/NK-LGLL. These findings contribute to support the utility of the STAT3 mutation analysis for diagnostic and prognostic purposes in LGLL.STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups: TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p < 0.05) blood counts of most normal leukocyte subsets, with a higher rate (vs. nonmutated LGLL) of neutropenia (p = 0.04), severe neutropenia (p = 0.02), and cases requiring treatment (p = 0.0001), together with a shorter time-to-therapy (p = 0.0001), particularly in non-Y640F STAT3-mutated patients. These findings confirm and extend on previous observations about the high prevalence of STAT3 mutations across different subtypes of LGLL, and its association with a more marked decrease of all major blood-cell subsets and a shortened time-to-therapy.

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BackgroundHigh levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters.MethodsThe TOCICOVID study included a prospective cohort of patients aged 16–80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology.ResultsAmong the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25–0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36–0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31–1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17–2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22–2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group.ConclusionThese data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-020-00911-6.

Mosunetuzumab Shows Promising Efficacy in Patients with Multiply Relapsed Follicular Lymphoma: Updated Clinical Experience from a Phase I Dose-Escalation Trial

Mosunetuzumab Shows Promising Efficacy in Patients with Multiply Relapsed Follicular Lymphoma: Updated Clinical Experience from a Phase I Dose-Escalation Trial

A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide with or without Pomalidomide in Patients with Relapsed and Refractory Multiple Myeloma

A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide with or without Pomalidomide in Patients with Relapsed and Refractory Multiple Myeloma

Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &amp;gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&amp;lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&amp;lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

A Comparison of Same Day Versus Next Day Administration of Pegfilgrastim in Lymphoma Patients Receiving CHOP Chemotherapy

Background Febrile neutropenia (FN) is a potentially life-threatening complication of myelotoxic chemotherapy, with increased incidence in patients with high risk chemotherapy or with patients with predisposing comorbidities in intermediate risk regimens. Prophylactic pegfilgrastim has been shown to decrease the incidence, duration, and severity of neutropenia, fever, and infection. Current guidelines recommend at least a 24-hour time lapse from chemotherapy to administration of growth factor; however, many cancer centers give same day growth factor due to convivence. Here, we explored lymphoma patients treated with CHOP+/-R (cyclophosphamide, doxorubicin, vincristine, prednisone, with or without rituximab) and received either same-day (within 24 hours of chemotherapy) or next-day (≥24 hours post chemotherapy) pegfilgrastim to address the safety and efficacy of administration timing in the real-world setting. Methods A retrospective, single center, cohort study was conducted between October 1, 2013 and October 1, 2016 to evaluate lymphoma patients who were treated with CHOP+/-R and given pegfilgrastim for prophylaxis at the University of Arizona Cancer Center. Patients were followed up to six cycles of chemotherapy. In the first cycle, 39 patients were identified: 33 patients received same-day pegfilgrastim and 6 patients received next-day pegfilgrastim. Primary data collected included the incidence of FN, neutropenia, dose reductions, antibiotic administration, and hospitalization rate. Results Two hundred and fourteen R-CHOP (0.90) or CHOP (0.10) chemotherapy cycles (187 cycles for the same-day and 27 cycles for the next-day) were evaluated in 39 patients. Among the first cycles (33 patients in the same-day and 6 patients in the next-day), there were no significant differences in the incidence of FN (0.21 vs. 0.00, P= 0.57), grade 3/4 neutropenia (0.39 vs. 0.33, P= 0.99) and hospitalizations (0.39 vs. 0.00, P= 0.08) between the same day and the next day groups. Among cycle two to six (154 cycles for the same-day and 21 for the next-day), there were no statistically significant differences in the incidence of FN (0.07 vs 0.05, P=0.99)grade 3/4 neutropenia (0.30 vs. 0.24, P= 0.80) and hospitalizations (0.11 vs 0.10, P= 0.99) between the same-day and next-day. The same-day group, had 33% percent of patients received reduced doses of CHOP or R-CHOP (median age= 80.0 yr). The incidence of FN was 0.11 in these patients and 0.06 in patients who received the usual doses (median age=65.5 yr) (P= 0.27). The incidence of grade 3/4 neutropenia was (0.34 vs 0.29, P=0.53) and hospitalizations (0.20 and 0.08, P=0.07) between patients who received reduced doses of chemotherapy because of age versus normal dosing respectively in the same-day arm. Conclusion In our analysis, we have shown that same-day was as safe and effective as next-day pegfilgrastim administration in lymphoma patients receiving CHOP+/-R. There was not a significant increase in FN in either group. Future prospective studies are warranted to investigate the practical benefits of same-day pegfilgrastim or its biosimilar. Potential future study directions could include addressing outcomes, side effects, patient satisfaction, and reduced healthcare costs associated with same-day administration of pegfilgrastim for the prophylaxis of FN. Table Disclosures Abraham: Coherus BioSciences: Research Funding, Speakers Bureau; Celgene: Consultancy; Terumo: Consultancy; Rockwell Medical: Consultancy; Janssen: Consultancy; Mylan: Consultancy; Sandoz: Consultancy; MorphoSys: Consultancy. McBride:Coherus BioSciences: Consultancy, Speakers Bureau; Merck: Speakers Bureau; Pfizer: Consultancy; Sandoz: Consultancy; MorphoSys: Consultancy; Bristol-Myers Squibb: Consultancy.

Real-World Characteristics of Patients with Peripheral T-Cell Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching

Introduction: In the phase 3 ECHELON-2 study (NCT01777152), treatment with brentuximab vedotin (BV) + cyclophosphamide, doxorubicin, and prednisone (A+CHP) demonstrated significantly longer progression-free and overall survival compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the frontline (FL) treatment of patients with systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL). This study supported the November 2018 US FDA approval of A+CHP as FL therapy for adults with sALCL or other CD30-expressing PTCL. The current analysis describes patient characteristics, PTCL subtypes, and supportive care use of FL A+CHP and CHOP outside of the clinical trial setting in the US. Methods: Using medical and pharmacy claims data in the Symphony Health Solutions database, a retrospective cohort analysis of patients with PTCL treated with FL A+CHP or CHOP was conducted to compare treatment and utilization characteristics. Patients ≥18 years with 1 inpatient or 2 outpatient ICD-9/10 PTCL diagnosis codes, newly initiated on A+CHP or CHOP (index date) between November 2018 and January 2020, and with ≥6 months continuous activity before and ≥3 months after the index date were included. To adjust for confounding factors, a 1:1 propensity score matching analysis was performed based on age, gender, baseline comorbidities, geographic region and length of follow-up. Results: A total of 755 patients met inclusion criteria (335 A+CHP; 420 CHOP) with a median follow-up period of 10.1 and 10.6 months, respectively. In the unmatched cohorts, 61% were male, and median age at index was 62 and 69 years for A+CHP and CHOP, respectively. The prevalence of comorbidities based on the Charlson Comorbidity Index was similar between the cohorts; prevalent conditions included diabetes, chronic pulmonary disease, congestive heart failure, and liver disease (Table 1). PTCL subtypes treated with A+CHP included sALCL (54%), PTCL-not otherwise specified (NOS; 27%), and angioimmunoblastic T-cell lymphoma (AITL; 13%); subtypes treated with CHOP included PTCL-NOS (35%), adult T-cell leukemia/lymphoma (ATLL; 35%), and AITL (11%) (Table 2). After matching, the proportion of patients who received granulocyte-colony stimulating factor (G-CSF; A+CHP: 91%, CHOP: 86%, p=0.1) and the incidence rate of neutropenia (A+CHP: 45%, CHOP: 42%, p=0.4) during FL treatment for both study cohorts was similar. Of patients who received G-CSF, the majority received it as primary prophylaxis given within the first 5 days of FL treatment initiation (A+CHP: 89%, CHOP: 85%, p=0.2). The rate of subsequent therapy (ie, therapy change after FL), was similar between A+CHP and CHOP (18% vs 21%; p=0.3) and for the sALCL subtype (16% vs 26%, p=0.2). Of the A+CHP patients who received subsequent therapy, 32% were retreated with a BV-containing regimen and 19% of CHOP patients received a BV-containing regimen. Conclusions: In this real-world analysis, US patients with PTCL newly initiated on A+CHP or CHOP were older (67 vs 58 years) than those in ECHELON-2. There was a high comorbidity burden; over half of the patients in both cohorts had 1+ comorbidities, a potential reflection of the older population. As would be expected due to a high rate of CD30-positivity in the disease, A+CHP was more commonly used than CHOP in sALCL. In PTCL subtypes in which CD30 is more variably expressed, A+CHP and CHOP were used with similar frequencies. Although clinical trials in ATLL have demonstrated improved outcomes with more complex and intensive regimens than CHOP, CHOP remains commonly used in ATLL. A+CHP was also used in PTCL subtypes not included in ECHELON-2, such as NK/T cell lymphomas. G-CSF was used as primary prophylaxis in the large majority of patients in both cohorts. The use of a BV-containing regimen as subsequent therapy was more common in A+CHP vs CHOP, probably because the tumors of A+CHP patients were more likely to have expressed CD30. Confounding by unmeasured characteristics cannot be ruled out due to inherent limitations in claims data (eg, lack of disease stage, CD30 testing and response outcomes). Characteristics and management of this real-world population with PTCL differed from those in the ECHELON-2 trial, demonstrating the importance of retrospective studies to assess the impact of new regimens on clinical practice and to identify areas for further education of practitioners. Disclosures Burke: Seattle Genetics: Speakers Bureau; Gilead: Consultancy; Bristol Myers Squibb: Consultancy; Roche: Consultancy; Epizyme: Consultancy; Adaptive: Consultancy; Kura: Consultancy; Morphosys: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Verastem: Consultancy; Astra Zeneca: Consultancy; Bayer: Consultancy; AbbVie: Consultancy. Liu:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Yu-Isenberg:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Fanale:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Surinach:Seattle Genetics: Research Funding. Flores:Seattle Genetics: Research Funding. Lisano:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Phillips:Beigene: Consultancy; AstraZeneca: Consultancy; Karyopharm: Consultancy; Bayer: Consultancy, Research Funding; Lymphoma Connect: Other; Incyte: Consultancy, Research Funding; Cardinal Health: Consultancy; University of Michigan: Current Employment; Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; BMS: Consultancy; Seattle Genetics: Consultancy.