scholarly journals Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5020-5020
Author(s):  
Wenrui Yang ◽  
Bing Han ◽  
Hong Chang ◽  
Bingyi Wu ◽  
Fankai Meng ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Real World ◽  
Overall Response Rate ◽  
Response Rate ◽  
Line Treatment ◽  
First Line ◽  
Overall Response ◽  
Treatment Naïve ◽  
First Line Treatment

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ombretta Annibali ◽  
Francesca Chiodi ◽  
Chiara Sarlo ◽  
Magdalena Cortes ◽  
Francesco M. Quaranta-Leoni ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Line Treatment ◽  
First Line ◽  
Indolent Disease ◽  
Anti Cd20 ◽  
First Line Treatment

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance.

Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

2011 ◽  
Vol 29 (30) ◽  
pp. 3968-3976 ◽  
Author(s):  
Atsushi Ohtsu ◽  
Manish A. Shah ◽  
Eric Van Cutsem ◽  
Sun Young Rha ◽  
Akira Sawaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Treatment

Purpose The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. Patients and Methods Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified. Conclusion Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.

A National Registry of Patients Diagnosed with Multiple Myeloma in Taiwan.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4955-4955
Author(s):  
Tzeon-Jye Chiou ◽  
Shang-Yi Huang ◽  
Cheng-Shyong Chang ◽  
Sheng-Fung Lin ◽  
Sung-Nan Pei ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
National Registry ◽  
Disease Stage ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Overall Response ◽  
Best Response ◽  
First Line Treatment

Abstract Abstract 4955 Background The diagnosis and treatment pattern in actual practice for patients with multiple myeloma has not been described in Taiwan. This is the first national registry survey with the introduction of conventional and novel anti-myeloma therapies in Taiwan. Methods The “Multiple Myeloma Observational Study” is a national-based observational registry survey conducted by the Hematology Society of Taiwan. All patients newly diagnosed with multiple myeloma within one year are eligible for inclusion. Information on treatment, treatment response and survival was obtained by medical record review. We report 115 patients with multiple myeloma in Taiwan who were enrolled from January 2006 to December 2008. Results The characteristics of 115 patients were examined according to age, gender and disease stage. The average age was 65 years. The number of male patient was 72 (62.6%); female patient, 43 (37.4%). The proportions of disease stage were: stage I, 14 (12.2%); stage II, 26 (22.6%); stage III, 75 (65.2%). All patients had received anti-myeloma agents as their first line treatment since diagnosis. The most commonly used regimen was combination of melphalan, prednisolone and thalidomide in 27 patients (23.5%) and combination of thalidomide and dexamethasone in 27 patients (23.5%); followed by combination of melphalan and prednisolone, 24 (20.9%); combination of vincristine, anthracycline and dexamethasone (VAD), 15 (13%), thalidomide alone, 9 (7.8%); dexamethasone alone, 5 (4.3%); combination of VAD and thalidomide, 2 (1.7%); others, 3 (2.6%). The adjunct therapies along with first line treatment include zoledronic acid, 59 (51.3%); clodronate, 16 (13.9%); pamidronat, 8 (7.0%); and epoietin, 5 (4.3%). The outcomes of treatment were also recorded. The overall response rate for first line treatment was 59.1%. The best response of combination of VAD and thalidomide was 100%, followed by combination of thalidomide and dexamethasone, 66.7%; combination of melphalan and prednisolone, 66.7%; the combination of melphalan, prednisolone and thalidomide, 63%, combination of vincristine, anthracycline and dexamethasone, 60%; thalidomide alone, 22.2%; dexamethasone alone, 20%. A total of 31 patients had received anti-myeloma agents as the second line treatment. The most commonly used treatment was thalidomide alone, received by 7 patients (22.6%); followed by combination of thalidomide and dexamethasone, 5 (16.1%); combination of melphalan, prednisolone and thalidomide, 5 (16.1%); VAD, 5 (16.1%); combination of melphalan and prednilolone, 3 (9.7%); dexamethasone alone, 3 (9.7%) and other regimen, 3 (9.7%). The overall response rate for second line treatment was 41.9%. The best response of the combination of melphalan, prednisolone and thalidomide, 66.7%, followed by combination of vincristine, anthracycline and dexamethasone, 60%; thalidomide alone 57.1%; the combination of thalidomide and dexamethasone, 40%. The median survival duration was still not achieved yet. Conclusions The results of this national registry show that the choice of treatments in multiple myeloma covers a wide range of therapeutic modality. The overall response of first line treatment and second line treatment was comparable to the result of other registry studies. Disclosures Chiou: Janssen-Cilag Taiwan: Honoraria, Research Funding. Lin:Janssen-Cilag Taiwan: Honoraria. Chang:Janssen-Cilag Taiwan: Honoraria. Hsiao:Janssen-Cilag Taiwan: Honoraria.

VTD (Bortezomib Plus Thalidomide Plus Dexamethasone) Followed By Autologous Stem Cell Transplantation As First Line Treatment for Multiple Myeloma: Real Life Results from a Single Institution

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5380-5380
Author(s):  
Salvatore Palmieri ◽  
Angela Gravetti ◽  
Stefano Rocco ◽  
Antonella Carbone ◽  
Carolina Copia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Salvage Therapy ◽  
Partial Remission ◽  
Response Rate ◽  
Real Life ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract BACKGROUND. In recent years, new classes of drugs have been introduced for the treatment of Multiple myeloma (MM). Several randomized trials have investigated, in the setting of first line treatment of patients eligible for autologous transplant (ASCT), the efficacy of the combination of two to four new and old drugs given as induction. Among these, VTD combination (bortezomib plus thalidomide plus dexamethasone) provided impressive results, so that it is now considered at different Institutions the standard of care as pretransplant therapy. However, data of VTD derive from clinical trials and should be verified in the "real life" setting, in terms of either efficacy or toxicity. AIMS. Here we present our experience in 76 MM patients treated between 2008 and 2014 with VTD as part of a first line treatment including also mobilization, single or double ASCT, and consolidation with two additional VD courses. No patient had been enrolled into a clinical trial. CHARACTERISTICS OF PATIENTS/METHODS. There were 39 males and 37 females, with a median age of 57 years (range 38-67). MM subtype was IgG=44 cases, IgA=15, IgD=1, micromolecular=13, non secreting=2, and solitary plasmocytoma=1. Stage according to Durie & Salmon was II-A=29, II-B=2, III-A=34 and III-B=10. In 8 cases single or multiple vertebroplasty was also necessary, while 7 patients had concomitant extramedullary plasmocytoma. In absence of CRAB criteria, patients were treated when progressive increase of M-component was observed. Treatment was given according to GIMEMA-MM-BO2005 protocol (Cavo et al, Lancet 2010) except for the following: from September 2012, bortezomib was given subcutaneously (in a total of 37 patients) and 4 instead of 3 induction cycles were given; mobilization therapy consisted of vinorelbine 30mg/sqm day 1 plus cyclophosphamyde 1500 mg/sqm day 2 (for further details, Annunziata et al, Ann Hematol 2006); consolidation did not include thalidomide and was given only from 2011; no maintenance therapy with dexamethasone was administered. RESULTS. Overall response rate after induction was 92% (70/76 patients), with 35 complete remission (CR), 25 very good partial remission (VGPR), 9 partial remission (PR) and one minimal response (MR). One patient was considered as stable disease and continued with the therapeutic program, 3 patients were refractory and were switched to salvage therapy, and 2 patients died during induction (due to fatal sepsis from H1N1 virus infection and multiorgan failure in a severely ill subject, respectively). After successful mobilization in 70/71 patients, single (n=34) or double (n=36) ASCT were given, depending on quantity of CD34+ cell collection, toxicity of first ASCT and response achieved. High dose melphalan was the conditioning regimen in all cases. After ASCT, response was upgraded in 24 cases (in 17 cases VGPR to CR, 4 PR to VGPR, 2 PR to CR, 1 MR to PR). Consolidation was given in all 47 programmed cases. Hematologic toxicity of VTD was negligible. Reduction of thalidomide schedule was necessary in 60 patients, while only 16 patients (21%) were able to complete the programmed days of therapy at 200 mg/day. In the remaining cases, 39 completed the therapy at 100 mg, 2 at 50 mg, while 19 had to definitely discontinue therapy after a median of 33 days (15-68). More frequent reasons of discontinuation or reduction were neuropathy, constipation, fatigue and skin rash; only 1 case of thrombosis was recorded in a non responding patient. Reduction of bortezomib dose was necessary only in 5 patients (all ev cases), all because of neuropathy. At the time of writing 57/76 patients (75%) are alive, with a median follow up of 27 months. The median duration of response was 38 months, 25/70 patients (36%) having progressed or relapsed. Depending on time to relapse (> or < 18 months), bortezomib or lenalidomide based salvage therapy was used. Overall and progression free survival (OS and PFS) are shown in figure 1. DISCUSSION. Our data demonstrate that the VTD combination in the real life is an extremely effective regimen in terms of response rate. Most patients after VTD are able to mobilize CD34+ cells as well as to receive ASCT. In a considerable proportion of cases reduction of thalidomide dose is required and in 25% of cases the drug needed to be discontinued. As compared to data from clinical trials, PFS in our series seems to be shorter, however our patients were unselected and in this series follow up is significantly longer. Disclosures No relevant conflicts of interest to declare.

Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group.

1997 ◽  
Vol 15 (5) ◽  
pp. 2090-2096 ◽  
Author(s):  
A Ardizzoni ◽  
H Hansen ◽  
P Dombernowsky ◽  
T Gamucci ◽  
S Kaplan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment ◽  
Sensitive Group

PURPOSE To assess activity and toxicity of topotecan in previously treated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS Patients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1) patients who failed first-line treatment < or = 3 months from chemotherapy discontinuation (refractory group); and (2) patients who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topotecan was administered as a 30-minute daily infusion at a dose of 1.5 mg/m2 for 5 consecutive days, every 3 weeks. RESULTS One hundred one patients were entered onto the study and 403 courses were administered. Ninety-two patients (47 refractory and 45 sensitive) were eligible and assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall median duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that of sensitive patients was 6.9 months (P = .002). Median survival of responding patients was 12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived, was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was reported in 39.3% of cycles and transient elevation of liver enzymes in 17%. CONCLUSION Topotecan has significant activity in SCLC, particularly in patients sensitive to prior chemotherapy, with predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted.

scholarly journals DOP54 Real-world effectiveness of thiopurine monotherapy in Crohn’s Disease: Is there still a place for thiopurines in the biological era?

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S089-S090
Author(s):  
A Rezazadeh Ardabili ◽  
S F G Jeuring ◽  
Z Mujagic ◽  
M J L Romberg-Camps ◽  
A A van Bodegraven ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Maintenance Therapy ◽  
Treatment Option ◽  
Real World ◽  
Population Based ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Background In current guidelines, thiopurines are still recommended as first-line maintenance therapy for patients with Crohn’s disease (CD). Due to their lack of immunogenicity, oral administration route and low costs, thiopurines are an attractive first-line treatment option. However, in recent studies the position of thiopurine monotherapy in CD has been questioned as a result of relatively lower overall effectiveness rates compared to ulcerative colitis. Real-world long-term effectiveness data substantiating the use and position of thiopurines in CD management remain sparse. We assessed long-term effectiveness of thiopurine monotherapy in CD using the population-based IBD South-Limburg (IBDSL) cohort. Methods All CD patients in the IBDSL cohort starting thiopurine monotherapy as first-line maintenance therapy between 1991–2014 were included. Thiopurine monotherapy was defined effective if either: (1) no escalation to biological treatment, (2) no course of corticosteroids, (3) no resective surgery or, (4) no hospitalization for active disease was required whilst on thiopurine treatment. Patients with early treatment discontinuation (i.e. &lt;3 months) were identified, including reason of discontinuation. Long-term effectiveness was assessed adjusting for differences in follow-up between patients using Kaplan-Meier analysis. Potential risk factors for therapy failure were identified using Cox regression. Results In total, 643/1162 (55.3%) CD patients (median follow-up: 8.5 years IQR 5.0–13.2) received first-line thiopurine monotherapy after a median of 9.7 months (IQR 3.2–31.3) after diagnosis. Therapy was discontinued within three months in 164 patients (25.5%), mainly due to adverse events [Figure 1]. Thiopurine monotherapy was effective for the duration of treatment in 229/479 (35.6%) patients, corresponding to estimated effectiveness rates of 62.9%, 43.9% and 31.2% after 1, 5 and 10 years, respectively [Figure 1–2]. No significant difference in effectiveness was observed after stratifying for era of thiopurine initiation (pre-biological (1991–1998) vs. biological (&gt;1999) era, p=0.84). Factors associated with thiopurine failure were stricturing disease (aHR 1.41, 95%CI 1.01–1.96) and upper GI involvement (aHR 1.52, 95%CI 1.02–2.28) at diagnosis. During follow-up, 40/229 patients with a durable response discontinued treatment due to quiescent disease. Of these, 35 patients (87.5%) remained without treatment 24 months after discontinuation. Conclusion Real-world data from this population-based study demonstrate that thiopurine monotherapy remains an effective and durable first-line treatment option for CD, even in the biological era. These results should be considered in the ongoing discussion regarding the position of thiopurine therapy.

scholarly journals Zanubrutinib, Lenalidomide Plus R-CHOP (ZR 2-CHOP) As the First-Line Treatment for Diffused Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3559-3559
Author(s):  
Huayuan Zhu ◽  
Yeqin Sha ◽  
Wei Wu ◽  
Jingyan Qiu ◽  
Yilian Yang ◽  
...  
Keyword(s):  
High Risk ◽  
Physical Condition ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
First Line ◽  
Pet Ct ◽  
Treatment Naïve ◽  
To Receive ◽  
First Line Treatment

Abstract Introduction To evaluate the safety and efficacy of zanubrutinib, lenalidomide plus R-CHOP (ZR 2-CHOP) as the first-line treatment for DLBCL patients, we conducted this single-arm retrospective observational study. Methods Treatment-naïve patients with DLBCL(including but not limited to double-hit, double expression) aged 18 to 75 years were enrolled.ZR 2-CHOP was given as follows, Oral zanubrutinib was given continuously (160 mg twice daily) from Day 0, lenalidomide 25 mg daily Day 1-7. Patients were administered intravenously rituximab (375 mg/m 2 Day 0), cyclophosphamide (750 mg/m 2 Day 1), doxorubicin (50 mg/m 2 Day 1), vincristine (1.4 mg/m 2 Day 1), and oral prednisone (100 mg Day 1-5). All patients were recommended to receive 6 cycles of ZR 2-CHOP (R-CHOP or R 2-CHOP were allowed in cycle 1-2 due to poor physical condition at treatment) and patients older than 70 years old were administered ZR 2-miniCHOP (Figure 1). CT or PET-CT scans were applied to mid-term efficacy and PET-CT scan was conducted after 6 cycles. ctDNA was dynamically detected before treatment, after 3 and 6 cycles to evaluate tumor mutational burden. The primary endpoint was complete response ratio (CRR) at mid-term and after 6 cycles. The secondary endpoint was overall response rate (ORR), ctDNA dynamics and adverse events (AE). AEs were graded based on CTCAE (version 5.0). Results 12 treatment-naïve DLBCL patients diagnosed in Pukou CLL Center were enrolled in this cohort between July 2020 and June 2021. The median age was 56 years old and all patients had ECOG-PS ≤2. 1 patient (1/12) was diagnosed as double-hit DLBCL and 9 patients (9/12) as double-expression. 10 patients were non-GCB and 2 were GCB. 7 patients were classified as high-intermediate and high-risk group according to NCCN-IPI (Table 1). At data cutoff (1st July, 2021), the median follow-up was 8 months (3-12 months) with all patients have completed at least 3 cycles and mid-term assessment has been conducted. The ORR was 100.0%, with 10 patients achieved CR and 2 patients achieved PR (both two patients received R-CHOP regimen in cycle 1/cycle 1-2 due to poor physical condition at initial treatment, Figure 1). 10 patients have received 6 cycles, all of them achieved CR (Figure 2). ctDNA was dynamically detected in six patients. The median number of detectable ctDNA mutation among six patients was 8 (0-12) with two patients classified as MCD subtype and one patients as EZB subtype. All six patients showed undetectable ctDNA after 3 cycles. During end of treatment follow-up, one patient (triple-hit, EZB) who scheduled to receive auto-SCT underwent disease progression 4 months later and reemergence of ctDNA showed previous homologous clones. The most common hematological toxicity events were lymphocytes count decreased, neutrophil count decreased, thrombocytopenia and anemia, with 3-4 level occurrence rate was 66.7%, 25.0%, 25.0% and 16.7%. The most common non-hematological toxicity events were nausea, fatigue and anorexia. One patients discontinued oral zanubrutinib and lenalidomide in last two cycles due to drug rash. Conclusion ZR 2-CHOP could attain high CR rate and ctDNA clearance in TN DLBCL, including patients with DEL and/or high-risk. The overall tolerability was manageable. ZR 2-CHOP could be one of the promising choice for TN DLBCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Zanubrutinib was used in the initial treatment of high-risk DLBCL.

Axitinib and avelumab (AA) as first-line treatment of metastatic renal cell carcinoma (mRCC): A real-world outcome review in the Northwest of England, United Kingdom.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 294-294
Author(s):  
Jennifer Allison ◽  
Natalie Charnley ◽  
Robert Stevenson ◽  
Tom Waddell ◽  
Manon Rhys Pillai
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitor ◽  
Risk Scores ◽  
Published Data ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

294 Background: The combination of the immune checkpoint inhibitor avelumab and VEGF-targeted, antiangiogenic tyrosine kinase inhibitor axitinib (AA) has demonstrated superior PFS and ORR compared to sunitinib in patients with mRCC and is an option for first line treatment across all IMDC risk scores. In this retrospective review we report our real world experience of this combination in three cancer centres in the Northwest of England. Methods: Treatment naïve mRCC patients receiving AA through the Early Access to Medicine Scheme at 3 cancer sites in the UK between May 2019 and July 2020 were identified. Primary outcomes of interest include overall response rate (ORR), adverse events (AEs) and preliminary survival observations. Results: A total of 44 patients were identified with a median follow up of 6.9 months (0.8-13.5 mo). Median age was 68 (48-81); 68% were male. The patients’ adult comorbidity evaluation score (ACE-27) was calculated: 0 = 43%, 1 = 30%, 2 = 7% and 3 = 20% . 45%, 48% and 7% of patients had favourable (F), intermediate (I) and poor (P) IMDC risk scores respectively. All had clear cell histology with 16% demonstrating sarcomatoid change. Most patients had undergone a nephrectomy (70%) and 36% had a single organ site of metastatic disease. ORR in the whole cohort was 60% (CR 5%, PR 55%, SD 25%, PD 2%, NE 13 %). Median time to first response was 2.6 months (0.6- 8.2mo). At time of data cut-off, 64% of patients remain on treatment (80% F, 48% I and 67% P). 14% of patients discontinued treatment due to disease progression while 22% stopped due to toxicity. The majority of patients (68%) continued axitinib at the starting dose of 5mg BD. Dose escalation of axitinib was possible in 9% patients while 23% needed a dose reduction due to toxicities. AEs were observed in 36 (82%) patients (G3 36%); the commonest being mucositis 30%; hypertension 23% (G3 11%); fatigue 25%; thyroid dysfunction 18%; diarrhoea 20% (G3 5%); hepatitis 20% (G3 11%). 9% of patients experienced an infusion reaction to avelumab. Overall, 9 (20%) patients received steroids for suspected immune related adverse events (irAEs); 6 (14%) were managed as G3≤ irAEs. 9 (20%) patients required inpatient admission due to AEs; 5 (11%) were associated with irAEs. Of the patients who discontinued AA treatment, 50% received subsequent therapy (12.5%, 75% and 12.5% receiving combination checkpoint inhibitor therapy, other VEFG TKi and TKi/MTOR combination respectively). 4 patients remain on active surveillance with no evidence of progression. Conclusions: Our early experience of AA in this real world setting reports comparable clinical responses to the published data. Treatment is well tolerated, with lower than expected levels of G3 or above AEs which is reassuring in a non-trial selected population. Follow-up is ongoing and updated efficacy and safety outcomes will be presented.

Lenvatinib (LEN) + pembrolizumab (PEMBRO) treatment in patients (pts) with metastatic clear cell renal cell carcinoma (RCC): Final results of a phase 1b/2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16542-e16542
Author(s):  
Chung-Han Lee ◽  
Amishi Yogesh Shah ◽  
James J Hsieh ◽  
Arpit Rao ◽  
Alvaro Pinto ◽  
...  
Keyword(s):  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Multiple Tumor ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Phase 1B ◽  
Metastatic Rcc ◽  
First Line Treatment

e16542 Background: Immune checkpoint inhibitors (ICIs) are commonly used as first-line treatment for pts with advanced RCC. In the recent phase 3 CLEAR trial, LEN + PEMBRO showed improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) vs sunitinib in first-line treatment of advanced RCC (Motzer R et al. NEJM. 2021). Additional treatment options are needed for pts with disease progression on ICIs. A phase 1b trial of LEN + PEMBRO was performed in multiple tumor types and included an expansion part into a phase 2 cohort of ICI-pretreated, treatment-naïve, or previously treated ICI-naïve pts with metastatic RCC (NCT02501096). We report the final results of the RCC cohort with an extended follow-up. Methods: Eligible pts were ≥18 years old and had measurable disease. Efficacy analyses were conducted by prior therapy grouping. The primary endpoint was ORR at week 24 (ORRwk24) per immune-related (ir) RECIST by investigator assessment. Secondary endpoints included ORR, duration of response (DOR), PFS, OS, and safety. Exploratory endpoints included tumor response assessed per RECIST v1.1 by independent review committee (IRC). Subgroup analyses of the ICI-pretreated group will be included in the poster. Results: The recommended doses determined in phase 1b were LEN 20 mg daily + PEMBRO 200 mg once every 3 weeks (Taylor M et al. JCO. 2020). The study enrolled 145 pts (efficacy analysis, n=143; safety analysis, n=145). At data cutoff (August 18, 2020), the median follow-up time was 19.8 months. The ORRwk24 was 55.8% (95% CI 45.7–65.5) for ICI-pretreated pts (n=104), 72.7% (95% CI 49.8–89.3) for treatment-naïve pts (n=22), and 41.2% (95% CI 18.4–67.1) for previously treated ICI-naïve pts (n=17). The median OS for the previously treated ICI-naïve pts was 30.3 months and was not reached in the other groups. Additional efficacy analyses are shown in the table. Treatment-related adverse events occurred in 99.3% of pts; the most common were fatigue (58.6%), diarrhea (55.2%), and hypertension (40.0%). Most pts (69%) maintained the LEN starting dose or were reduced to LEN 14 mg daily (dose level −1). Conclusions: LEN + PEMBRO demonstrated promising antitumor activity with a manageable safety profile in pts with metastatic RCC, including pts who were ICI-pretreated. Clinical trial information: NCT02501096. [Table: see text]

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