Response to Bortezomib Therapy for Multiple Myeloma (MM) in Actual Clinical Practice: Preliminary Effectiveness Findings of an International Observational Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4837-4837
Author(s):  
Michel Delforge ◽  
Eirini Katodritou ◽  
Konstantinos Zervas ◽  
Deniz Sargin ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Safety Data ◽  
Response Rates ◽  
Complete Response ◽  
Response Criteria ◽  
Actual Clinical Practice ◽  
Overall Response ◽  
Prior Therapy ◽  
Best Response

Abstract Background: Bortezomib (VELCADE®) is indicated for the treatment of MM in patients (pts) who have received at least 1 prior therapy. The electronic VELCADE Observational Study (eVOBS) is designed to evaluate the clinical and outcomes benefits of bortezomib in actual clinical practice. The study is open for enrollment between October 2006 and December 2008 in Belgium, France, Greece, Russia, Spain, Sweden, and Turkey with 3-year follow up. This report includes preliminary outcomes in pts with at least 4 months of data as of July 2007. Methods: Adults were eligible for study if they were scheduled to initiate bortezomib within the approved indication. All bortezomib dosages and concomitant treatments were permitted, except investigational therapies. Data on concomitant therapies, treatment response, and safety were collected prospectively during bortezomib therapy. Due to the non-interventional nature of the study, no predefined response criteria were mandated; response criteria could include M-protein, EBMT, SWOG, or others as defined by the investigator. Results: A total of 86 pts with at least 4 months of data were included in this analysis. Median age was 61 yrs, and 50 (58%) pts were male. Median interval since diagnosis was 3 yrs. The number of previous therapies for MM was 1, 2–3, and ≥4 for 38%, 44%, and 11% of pts, respectively. Demographic and clinical characteristics of the initial participants were similar to those of the participants in the prospective controlled phase 3 APEX trial (Richardson, N Engl J Med, 2005:352; 2487–98). Most pts (61%) received bortezomib with dexamethasone. Adverse events (AEs) were reported in 61 (71%) pts, including Grade ≥3 AEs in 38% and Grade ≥4 AEs in 9%. AEs were treatment-related in 45% of patients and treatment-limiting in 9%. Presently, 72 of 86 pts have been evaluated for response, of whom 54 completed 4 or more cycles. Response rates are shown in the table. Updated data will be presented at the meeting. Best Response(n = 72) Complete response (CR) 5 (7) Near complete response (nCR) 9 (13) Partial response (PR) 30 (42) Minimal response (MR) 9 (13) Stable disease (SD) 6 (8) Progressive disease (PD) 13 (18) Overall response (≥PR) 44 (61) Overall response (≥MR) 53 (74) Conclusions: In this preliminary analysis of data from a prospective, observational study of actual clinical practice, most pts received bortezomib in combination with 1 or more other therapies for MM. Overall response in actual clinical practice was at least as common as previously reported with bortezomib monotherapy. Response rates and safety data from actual clinical practice demonstrate that bortezomib-containing regimens are effective and well-tolerated in the treatment of MM.

Efficacy of naxitamab in patients with refractory/relapse (R/R) high-risk neuroblastoma (HR-NB) by bone/bone marrow (BM) evaluation, potential sites of residual disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10022-10022
Author(s):  
Brian H. Kushner ◽  
Daniel A. Morgenstern ◽  
Karsten Nysom ◽  
Melissa K. Bear ◽  
Karen Tornøe ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Safety Data ◽  
The United States ◽  
Outpatient Setting ◽  
Minor Response ◽  
Overall Response ◽  
Gm Csf ◽  
Prior Therapy ◽  
Meaningful Activity

10022 Background: NB is the most common extracranial solid tumor in children and half of patients present with high-risk disease. Bone and BM are frequent sites of metastatic disease and can serve as a reservoir for residual disease driving relapse. Naxitamab, a GD2-binding monoclonal antibody, was recently approved in the United States in combination with GM-CSF for the treatment of pediatric patients ≥1 year of age and adult patients with R/R HR-NB in the bone/BM who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe outcomes from the registrational Trial 201 (NCT03363373) detailed by bone/BM involvement. Methods: HR-NB patients with primary refractory disease or incomplete response to salvage treatment following relapse or progressive disease (PD) (in both cases including SD, MR and PR) with disease limited to bone and/or BM were eligible. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3 mg/kg/infusion (9 mg/kg/cycle) in combination with GM-CSF at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Response was assessed after Cycle 2 and then every 2-3 months by revised International Neuroblastoma Response Criteria (INRC) using BM biopsies/aspirates and 123I-MIBG scintigraphy or FDG-PET. Effectiveness was concluded if the lower limit of the Clopper-Pearson exact 95% confidence interval (CI) of overall response rate (ORR) was >20%. We report efficacy data on 22 patients and safety data on the first 25 patients enrolled. Results: 13 (59%) patients had NB in bone, 2 (9%) had NB in BM, and 7 (32%) had NB in both bone and BM. Summary of overall response and response by compartment. Conclusions: Naxitamab provided clinically meaningful activity in both bone and BM with ORR of 68% and had a manageable AE profile. Clinical trial information: NCT03363373. [Table: see text]

Ipilimumab in real-world clinical practice: efficacy and safety data from a multicenter observational study

2017 ◽  
Vol 29 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Alberto Russi ◽  
Vera Damuzzo ◽  
Marco Chiumente ◽  
Jacopo Pigozzo ◽  
Marco Cesca ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Real World ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Multicenter Observational Study

scholarly journals Low-Dose Radiotherapy Versus Moderate-Dose Radiotherapy for the Treatment of Indolent Orbital Adnexal Lymphomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Jonathan Baron ◽  
Christopher M. Wright ◽  
Daniel Y. Lee ◽  
Maribel Carpenter ◽  
Shwetha H. Manjunath ◽  
...  
Keyword(s):  
Low Dose ◽  
Response Rates ◽  
Complete Response ◽  
Moderate Dose ◽  
Exact Test ◽  
Overall Response ◽  
Low Dose Radiotherapy ◽  
Kaplan Meier ◽  
Grade 3

PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 – 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher’s exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

Observing patients with advanced non-small cell lung cancer (NSCLC): An overview of real world treatments and outcomes in Europe

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7626-7626
Author(s):  
H. G. Bischoff ◽  
H. Anderson ◽  
B. van den Borne ◽  
F. Langer ◽  
M. I. Leschinger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Observational Study ◽  
Large Scale ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Complete Response ◽  
First Line ◽  
Best Response ◽  
Clinical Trial Results

7626 Background: ACTION (Assessment of Costs and ouTcomes of chemotherapy In an Observational setting in patients with advanced NSCLC) is a prospective, pan-European observational study. The objective of ACTION is to describe advanced NSCLC treatment in routine clinical practice. Methods: Chemonaive patients (pts) aged = 18 yrs with stage IIIb/IV NSCLC were observed for 18 months from presentation for initiation of chemotherapy (CT). All pt care, including CT given, was at the discretion of the pt/physician. Pts were excluded if participating in a clinical trial. Results: 975 pts [Germany (571), UK (193), Finland (99), Netherlands (76), Portugal (36)] were enrolled from April 2003 to September 2004 and observations completed June 2006. Median age was 65 yrs (32–90) with 28.3% of pts aged =70 yrs; 71.3% were male; 65.2% had stage IV disease. WHO performance status (PS) was 0/1 (86.2%), 2 (10.0%), 3/4 (3.8%). Of 487 pts who experienced weight loss, 172 (33.4%) lost >10% body weight in 4 weeks prior to start of CT. First-line CT given: gemcitabine (gem) 10.3%, vinorelbine (vin) 4.3%, gem+platinum 45.0%, vin+platinum 14.6%, taxane+platinum 11.7%, other 14.2%. Complete response (CR) to first-line CT was observed in 1.8% of pts, partial response (PR) 37.9%, stable disease (SD) 28.5%, progressive disease (PD) 17.8%, unknown 13.8%. Second-line CT was planned for 29.2% (285) pts. Median time from initiation of 1st-line to initiation of 2nd-line CT was 5.8 months. Median age was 62 yrs (32–84); 69.8% were male; WHO PS at initiation of 2nd line CT: 0/1 (79%), 2 (17%), 3/4 (4%). Best response to 2nd-line CT: CR 0.4%, PR 9.1%, SD 19.3%, PD 48.8%, unknown 14.3%. Unadjusted median survival time for all pts: 9.3 months (95% CI 8.6–10.3). Overall estimated 1-yr survival was 39.5%. Conclusions: ACTION was the first large-scale observational study in pts with advanced NSCLC in Europe. Overall response rates and survival were consistent with clinical trial results, even though approximately one- third of pts enrolled may have been excluded from clinical trials on the basis of their baseline demographics. No significant financial relationships to disclose.

Comparison of three different radiation fractionation schedules in the palliation of painful bone metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9055-9055
Author(s):  
Monica Malik ◽  
Swapna Jilla ◽  
Nanditha Sesikeran ◽  
K. V. Jagannath Rao Naidu ◽  
Suresh Pamidighantam ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Pain Score ◽  
Performance Status ◽  
Response Rates ◽  
Complete Response ◽  
Analgesic Requirement ◽  
Single Fraction ◽  
Overall Response ◽  
Painful Bone Metastases

9055 Background: The purpose of this study was to compare the efficacy of a single fraction versus two multifractionated regimens in the palliation of painful bone metastases. Methods: Patients with painful bone metastases were randomized into three groups. Group I received a dose of 8 Gy in a single fraction, Group II received 20 Gy in five fractions and Group III patients received 30 Gy in 10 fractions. Pain score, ECOG performance status and analgesic requirement were recorded at baseline and at 1, 4, 8 and 12 weeks following treatment. Pain score was recorded on a 5-point verbal rating scale from 0 (no pain) to 4 (extremely severe pain). Overall response was defined as decrease in pain score by at least one point. Complete response was defined as achieving a pain score of zero at any point during follow-up. Duration of overall response was defined as the time from initial response till return of pain to its baseline value. Results: 45 patients were included with 15 in each group. Median age was 55 years (range 29-78 years). 17(37.7%) had metastasis in pelvic bones; 17(37.7%) in the spine while the remainder in the appendicular bones. Overall response rates in Groups I, II and III at week 1 were 60%, 53.3% and 60% respectively (p=0.71). At 1 month, overall response rates were 71.4%, 73.3% and 73.3% (p=0.84) and at 3 months; 78.5%, 80% and 80% respectively (p=0.86). The rate of complete response in all the three groups was 20%. Improvement in performance status in Groups I, II and III was seen in 60%, 66% and 80% respectively (p=0.69). Analgesic usage decreased in 86%, 87% and 80% patients in groups I, II and III respectively (p=0.66). Out of the nine complete responders, two sustained the response for less than four weeks, four patients up to eight weeks and remaining three till the end of follow-up. There was no statistically significant difference in between the three arms among all the variables compared. Conclusions: All three groups showed equal efficacy in pain palliation, analgesic requirement, improvement in performance status and duration of response. In patients with very advanced disease and short life expectancy, where the treatment goal is to decrease pain, 8 Gy in single fraction is a convenient and cost effective schedule.

A Multiple Myeloma Research Consortium (MMRC) Multicenter Phase I Trial of Perifosine (KRX-0401) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (MM): Updated Results.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1169-1169 ◽  
Author(s):  
Andrzej Jakubowiak ◽  
Todd Zimmerman ◽  
Melissa Alsina ◽  
Paul Richardson ◽  
Jonathan Kaufman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Phase 1 ◽  
Complete Response ◽  
Toxicity Assessment ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Prior Therapy ◽  
Best Response

Abstract INTRODUCTION: Perifosine (Peri) a novel, oral signal transduction modulator with multiple effects including inhibition of Akt and activation of JNK, has demonstrated clinical activity when combined with dexamethasone (Dex) in patients (pts) with relapsed/refractory MM (ASH 2006 #3582). Lenalidomide (Revlimid, Rev) a novel, oral immunomodulatory drug has additive effects when combined with Dex. Pre-clinical studies demonstrate increased cytotoxicity against MM cells when Peri is combined with Rev/Dex compared to each drug alone or in combination (Hideshima, T.et al Data on File). The addition of Peri to Rev/Dex may therefore enhance its clinical activity. This phase 1 study aimed to determine MTD and activity of Peri + Rev + Dex, in pts with 2nd or 3rd line MM. METHODS: Four cohorts (6 pts each) are planned, dosing Peri at 50 or 100mg (daily), Rev 15 or 25mg (d 1–21) and Dex 20mg (d 1–4, 9–12 and 17–20 for 4 cycles, then 20 mg d 1–4) in 28-d cycles. Toxicity assessment uses NCI CTCAE v3.0; DLT is defined as grade (G) 3 non-hematologic toxicity, G4 neutropenia for 5 d and/or neutropenic fever, or platelets <25,000/mm3 on >1 occasion despite transfusion. Response is assessed by modified EBMT criteria. RESULTS: 12 pts (6 M / 6 F, median age 62 y, range 40 – 78) have been enrolled; 6 pts in cohort 1 (Peri 50mg, Rev 15mg, Dex 20mg) and 6 pts in cohort 2 (Peri 50mg, Rev 25mg, Dex 20mg). 7 pts (58%) had relapsed/refractory MM, with a median of 2 lines of prior treatment (range 1–3). Prior therapy included dex (100%), thalidomide (83%), bortezomib (58%), stem cell transplant (67%) and one patient who had relapsed on prior Rev/Dex. 10 pts have completed one full cycle of treatment and the most common adverse events (≥ 10%) have been as follows: Adverse Event Grade 1 Grade 2 Grade 3 Nausea 10% 0% 0% Vomiting 10% 0% 0% Diarrhea 30% 10% 10% Fatigue 20% 20% 10% Thrombocytopenia 10% 10% 20% Increase Creatinine 10% 10% 0% Neutropenia 0% 0% 20% Leukopenia 0% 0% 20% No DLT’s or G 4 events have been reported. Rev was reduced in 1 patient and dex was reduced in 3 pts. 9 of 12 pts are evaluable for response, with best response (EBMT and Uniform criteria) after ≥ 2 cycles was as follows: Response N (%) Duration (wks) Near Complete Response (nCR) 1 (11%) 28+ Very Good Partial Response (VGPR) 1 (11%) 21+ Partial Response (PR) 3 (33%) 31+, 12+, 8+ Minimal Response (MR) 1 (11%) 21+ Stable Disease (SD) < 25% reduction in M-protein 1 (11%) 16 Progressive Disease (PD) 2 (22%) 8, 4 7/10 pts remain on study. CONCLUSIONS: Pts to date have tolerated Peri + Rev + Dex well with no unexpected toxicities and clinical activity has been noted within the first 2 cohorts with 5 of 9 (56%) of pts achieving at least PR. To limit dex-related toxicities, the protocol will be amended to use weekly Dex as per Rajkumar et al. (ASCO 2007), which will apply to cohorts 3 and 4. Accrual is ongoing and additional results will be updated at the meeting.

Characterization of Patients with Multiple Myeloma Achieving Complete Response to Bortezomib: An Interim Report From An International Electronic Observational Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4938-4938
Author(s):  
Michel Delforge ◽  
Hadewijch De Samblanx ◽  
Maria Roussou ◽  
Konstantinos Zervas ◽  
Eirini Katodritou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Clinical Practice ◽  
Observational Study ◽  
Complete Response ◽  
Practice Setting ◽  
Employment Equity ◽  
Clinical Practice Setting ◽  
Equity Ownership ◽  
Response Groups

Abstract Abstract 4938 Introduction Bortezomib (Velcade®) is effective and well tolerated in patients with multiple myeloma (MM), including those with adverse prognostic factors such as advanced age, more prior lines of therapy, and advanced-stage disease. The international, non-interventional, Electronic Velcade Observational Study (eVOBS) is an ongoing observational study that aims to assess the clinical and health economic outcomes in MM patients treated with bortezomib in the clinical-practice setting. In this study, we characterized patients achieving complete response (CR) with bortezomib in the relapsed/refractory setting, and assessed the effects of adverse prognostic factors on the rate of CR. Methods Adult patients from Belgium, France, Greece, Russia, Spain, Sweden, and Turkey scheduled to receive bortezomib for relapsed MM were eligible for inclusion in eVOBS. All bortezomib doses and concomitant treatments (except investigational therapies) were permitted; dose adjustments and cycle delays were documented. Patients are being followed for up to 3 years to document long-term outcomes; data are collected at baseline and at the end of every bortezomib cycle. Due to the non-interventional nature of the study, no predefined response criteria were mandated; response criteria were defined by the investigator and may have included European Group for Blood and Marrow Transplantation (EBMT), Southwest Oncology Group (SWOG), or M-protein criteria. Patients who had at least 12 weeks data or who had died by the time of data cut-off (June 30, 2009) were included in this exploratory analysis; patients were assessed after completion of four and six cycles. Results A total of 769 patients were included, 129 (16.8%) of whom achieved CR. There were no significant differences in baseline characteristics between patients who did (n=129) vs did not (n=640) achieve CR: 49.8% vs 47.3% were male, median age at baseline was 60.6 vs 62.1 years, median age at diagnosis was 57.9 vs 59.4 years, and median time since diagnosis was 2.3 vs 2.4 years. Patients with adverse prognostic factors were evenly distributed among response groups: of the patients who achieved CR, 7.8%, 55.8%, 23.3%, and 13.2% had 0, 1, 2, and 3 or more prior lines of therapy, vs 3.6%, 56.1%, 23.4%, and 15.8% of those who did not achieve CR. Similar results were seen for patients across disease stages: 14.7%, 31.0%, and 46.5% of CR patients vs 12.3%, 33.1%, and 50.2% of non-CR patients had ISS disease stage I, II, or III, respectively. Similarly, patients with comorbidities such as obesity or diabetes were evenly distributed across response groups: 6.1% and 7.1% of CR patients had obesity or diabetes, respectively, vs 4.4% and 9.6% of non-CR patients. After 4 cycles, the overall response rate (ORR) in patients who had completed 4 cycles (n=518) was 70%, including 12% complete response (CR), 16% near-CR (nCR), and 42% partial response (PR). Improved response rates were seen with prolonged therapy; after 6 cycles, the ORR in patients who had completed 6 cycles (n=321) was 82%, including 16% CR, 20% nCR, and 46% PR. As shown in the Figure, analysis of overall survival by best response at cycle 4 showed that achieving a CR/nCR is associated with significantly improved survival versus PR (p<0.0001). Conclusions Together, these results show that bortezomib, as administered in the clinical-practice setting, is highly active in relapsed/refractory MM patients, with CRs achieved among all patient subgroups. Furthermore, achievement of CR appears associated with prolonged survival and responses to bortezomib appear to improve with prolonged duration of therapy. Disclosures Delforge: Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria. Hulin:Janssen-Cilag: Honoraria; Celgene: Honoraria. Ganguly:Johnson & Johnson: Employment, Equity Ownership. Diels:Johnson & Johnson: Employment, Equity Ownership. Dhawan:Johnson and Johnson Research Pharmaceuticals: Employment. Dimopoulos:Millennium Pharmaceuticals, Inc.: Honoraria; Ortho-Biotech: Consultancy, Honoraria.

scholarly journals Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real-World Clinical Practice: Data from a Belgian Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1744-1744 ◽  
Author(s):  
Timothy Devos ◽  
Koen Theunissen ◽  
Fleur Samantha Benghiat ◽  
Alain Gadisseur ◽  
Stef Meers ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Median Time ◽  
Real World ◽  
Research Funding ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Best Response ◽  
History Of ◽  
T315i Mutation

Abstract Background Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for adult patients with resistant or intolerant chronic phase (CP), accelerated phase, or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), or those with the T315I mutation. In Belgium, ponatinib has been commercially available since March 2016. The goal of this registry was to collect efficacy and safety data in CML and Ph+ ALL patients and to evaluate ponatinib in routine clinical practice in Belgium. Methods This ongoing, prospective, multi-center registry includes patients ≥18 years of age with CML or Ph+ ALL, who have initiated ponatinib treatment. Demographic, efficacy and safety data were collected for patients enrolled from March 2016 (day 0) onwards. Results up to study month 24 are presented. Data were analyzed by descriptive statistics. Ethics Committee approval was obtained and all patients provided informed consent. Results At time of data analysis, 34 patients (21 CP-CML and 13 Ph+ ALL) were enrolled. The median age of CP-CML and Ph+ ALL patients was 57 and 55 years, respectively. Patients were heavily pretreated: 90% of CML and 92% of Ph+ ALL patients had received ≥2 prior TKIs. Several patients had one or more risk factors for TKI cardiovascular toxicity: hypertension (10), history of cardiovascular disease (11), smoker (10), hypercholesterolemia (5), and diabetes (4). Median follow-up was 539 days for CML and 135 days for Ph+ ALL patients. The reasons for starting ponatinib therapy were related to refractoriness to previous TKIs (36%), progression (18%), presence of the T315I mutation (18%) or intolerance (29%). Eighty percent (8/10) of the patients who started ponatinib due to intolerance to previous TKIs had received ≥3 prior TKIs. At entry, 17 of the 34 patients (50%) had a confirmed BCR-ABL mutation. Of these 17, 10 (59%; 5 CML and 5 Ph+ ALL) had the T315I mutation. Starting doses of ponatinib in CML patients were 45 mg (76%), 30 mg (10%) and 15 mg (14%) once daily. Starting doses in Ph+ ALL patients were 45 mg (85%), 30 mg (8%) and 15 mg (8%). At latest follow up, the median treatment duration for the 21 CML patients was 531 days (range 15 - 2483) and for the 13 Ph+ ALL patients it was 123 days (range 13 - 1945). Best response was a major molecular response (MMR), which was obtained in 71% of CML patients and 38% of Ph+ ALL patients. The median time-to-best response was 175 days in CML and 35 days in Ph+ ALL patients. In the 10 patients (7 CML and 3 Ph+ ALL) who started ponatinib because of intolerance to several previous TKIs, 80% achieved MMR. The median time to achieve best response in these patients was 192 days for CML and 31 days for Ph+ ALL patients. Treatment-related adverse events (AEs) were reported in 20 patients (59%); the most common were rash (26%), dry skin (9%) and constipation (9%). Three patients reported ≥1 treatment-related serious AE (SAE): thrombocytopenia (n=1), cholecystitis (n=1) and hepatocellular injury (n=1). Three serious cardiovascular events were observed in 1 patient, who had a history of congenital cardiomyopathy and aortic prosthesis. They were scored as not related to ponatinib. Dose reductions or interruptions occurred in 33 cases (20 in CML and 13 in Ph+ ALL patients), with the following reasons most frequently mentioned: AEs (76%), to prevent AEs (18%) and other (6%). Dose increases occurred in 12 cases (10 in CML and 2 in Ph+ ALL patients), for the following reasons: good tolerance of treatment (58%), no or low response (33%) or other (8%). At time of analysis, 19 patients (9 CML and 10 Ph+ ALL) had discontinued treatment, of which 32% due to AEs, 5% due to an SAE, 21% due to planned allogeneic transplant, 16% due to disease progression and 26% due to other reasons. [Note: Percentages may not total 100 due to rounding] Conclusion Real-world evidence from this Belgian registry shows that ponatinib has a favorable efficacy and safety profile in, and supports its use in CML and Ph+ ALL patients who are resistant or intolerant to previous therapies or those with the T315I mutation. Deep molecular responses were obtained in the majority of patients. No new safety signals emerged with ponatinib treatment than those previously reported. Funding: Incyte Biosciences Benelux BV Disclosures Devos: Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Theunissen:Incyte: Honoraria. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Kuipers:Incyte Biosciences Benelux BV: Employment.

scholarly journals Patterns of Care and Clinical Outcomes in Peripheral T-Cell Lymphoma Patients Receiving First-Line Treatment in Routine Clinical Practice in France and the United Kingdom

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3482-3482
Author(s):  
Christopher P Fox ◽  
Ajibade O Ashaye ◽  
Ruchit Shah ◽  
Shelby Corman ◽  
Mehul Dalal ◽  
...  
Keyword(s):  
Clinical Practice ◽  
T Cell ◽  
Pharmaceutical Company ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Best Response ◽  
Wholly Owned Subsidiary ◽  
The Uk

INTRODUCTION Peripheral T cell lymphomas (PTCL) are a rare and heterogenous group of aggressive non-Hodgkin lymphomas (NHL) that develop from mature T- and natural killer cells. They comprise approximately 10% of all newly diagnosed cases of NHL in Western populations. The current study characterizes real-world treatment patterns and outcomes among patients with PTCL in France and the United Kingdom (UK) in the first-line (1L) setting. METHODS A retrospective medical chart review study was undertaken at geographically disparate clinical sites in France and UK, where treating physicians were responsible for patient selection and data collection via structured case report forms. Adults (≥18 years) with newly diagnosed with PTCL between January 1, 2014 and December 31, 2016 were randomly selected for inclusion in the study. Eligible patients had received at least 1L treatment (1LT) for PTCL and had available clinical data for ≥1 year after PTCL diagnosis or until death. Patients enrolled in a clinical trial for 1L PTCL at any time between diagnosis and end of follow-up or who had any prior unresolved malignancy within 5 years of PTCL diagnosis were excluded. Demographic, clinical, and immunophenotypic/cytogenetic profiles of PTCL patients were assessed at diagnosis. Treatments received and best response as reported by the treating clinician (categorized as complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) at the end of 1LT are described. Data from both countries were pooled for the current analysis. RESULTS Overall, 32 haematologist/oncologists (France, 15; UK, 17) with a median of 12.5 years of clinical practice participated in the study. Most physicians in France practiced at a university hospital or a regional hospital centre (73.3%). In the UK, most physicians practiced at a specialist cancer/ tertiary referral treatment centre (47.1%). A total of 109 patients (France, 53; UK, 56) received at least 1L PTCL treatment during the study period. The median age at diagnosis was 63 years (range, 19 to 84 years), with a male predominance (57.8%). Eighty percent of patients had an ECOG performance status of 0-1 at diagnosis. B symptoms were present in 59.6% and extranodal disease was present in 35.8% patients at diagnosis. Most patients (72.5%) had stage III or IV disease and (64 of 102) 62.75% were classified as intermediate risk (score of 2-3) as per the International Prognostic Index. The most common histological subtypes were PTCL-not otherwise specified (NOS) (37.6%), angioimmunoblastic T-cell lymphoma (29.4%), and systemic anaplastic large cell lymphoma (20.2%). The median duration of follow-up was 34 months from the start of 1L PTCL treatment. Of those tested, 60.4% patients were positive for CD30 (information on threshold was not reported). Only 19.3% patients underwent testing for any cytogenetic marker. During follow-up, 28.4% of patients had died. In the 1L setting, 59.6% and 26.6% patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and with CHOEP/CHOEP‐like regimens (Table). Median duration of 1LT was 4.9 months. Stem cell transplant was undertaken in 29.4% patients as part of 1L treatment, of which 84.4% were autologous. PET-CT was used for response assessment in 56% of patients. Best response within 1 year of completing 1LT and before start of 2L treatment was assessed in 75/109 [68.8%] patients (Table); of whom 80% (60 patients) were reported to have a complete response (Table), and about 39% relapsed (within the first year) and went on to 2L treatment. The remaining 27 patients had best response assessed prior to completion of 1LT. Brentuximab vedotin (19%) and GemOx (19%) were the most common 2L treatments. CONCLUSIONS This retrospective observational study describes treatment patterns and key clinical outcomes among patients receiving 1L PTCL treatment in France and the UK. CHOP-based regimens were used to treat 59.6% of the study patients. Understanding distribution of PTCL subtypes and outcomes of treatment in routine clinical practice is complementary to data derived from clinical trials and crucial to facilitate improvement of survival outcomes through the introduction of novel therapies for this challenging group of rare malignancies. Disclosures Fox: Janssen: Consultancy; Adienne: Other: Travel Support; Takeda Pharmaceuticals: Consultancy; Atara Biotherapeutics: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Sunesis: Consultancy. Ashaye:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd: Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Shah:Pfizer: Research Funding; Merck: Research Funding; Bayer: Research Funding. Dalal:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Truemper:Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy; Roche: Research Funding; Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding.

Pemigatinib for previously treated locally advanced/metastatic cholangiocarcinoma (CCA): Update of FIGHT-202.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4086-4086
Author(s):  
Ghassan K. Abou-Alfa ◽  
Vaibhav Sahai ◽  
Antoine Hollebecque ◽  
Gina M. Vaccaro ◽  
Davide Melisi ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Safety Data ◽  
Progression Free Survival ◽  
Complete Response ◽  
Treatment Interruption ◽  
Primary Data ◽  
Efficacy And Safety ◽  
Prior Therapy ◽  
Duration Of Response

4086 Background: Pemigatinib (PEMI), a potent, selective, oral FGFR1-3 inhibitor, has shown efficacy and safety in patients (pts) with CCA and FGFR2 rearrangements/fusions in FIGHT-202 (NCT02924376; objective response rate [ORR], 35.5%; duration of response [DOR], 7.2 months [mo]). Overall survival (OS: 21.1 mo) was not mature in the primary report (Abou-Alfa. Lancet Oncol 2020; cutoff: Mar 22, 2019); herein we report matured efficacy and safety data from FIGHT-202 (cutoff: Apr 7, 2020). Methods: Pts (≥18 y) with known FGF/FGFR alterations and progression after ≥1 prior therapy had FGFR2 rearrangements/fusions (cohort A), other FGF/FGFR alterations (B), or no FGF/FGFR alterations (C). Pts received PEMI 13.5 mg QD (21-d cycle; 2 wks on, 1 wk off) until progression or toxicity. Primary endpoint: independent, centrally confirmed ORR (cohort A); secondary endpoints: ORR (cohorts B, C; cohorts A and B combined); DOR, disease control rate (DCR), progression free survival (PFS), OS, and safety. A post-hoc analysis in cohort A evaluated mOS in responders (pts with complete response [CR] or partial response [PR]) vs non-responders (pts with progressive disease [PD] or stable disease (SD]). Results: At cutoff, 147 pts were enrolled (cohort A, n=108; B, n=20; C, n=17; FGF/FGFR status undetermined, n=2); median follow-up was 30.4 (range, 4.9–38.7) mo and median treatment duration was 5.9 (0.2–36.5) mo. In cohort A, 9.3% of pts remained on therapy at cutoff; in cohorts B and C, all pts had discontinued. Pts discontinued mainly for PD (67.6%, 75%, and 64.7% in cohorts A, B, and C respectively). Independent, centrally confirmed ORR was 37.0%; mOS was 17.5 mo (95% CI, 14.4-22.9) in cohort A (Table 1). mOS for responders (n=40) vs non-responders (n=68) was 30.1 (95% CI, 21.5-NE) mo vs 13.7 (9.6-16.1) mo. Overall, most common all-cause treatment-emergent adverse events (TEAEs) were hyperphosphatemia (58.5%; grade ≥3, 0%), alopecia (49.7%; 0%), diarrhea (46.9%; 3.4%), fatigue (43.5%; 5.4%), nausea (41.5%; 2%), and dysgeusia (40.8%; 0%); 10.2%, 13.6% and 42.2% of pts discontinued, had dose reduction, and treatment interruption due to TEAEs, respectively. Conclusions: These results reinforce the primary data, showing continued, durable responses and sustained tolerability in pts receiving PEMI for CCA harboring FGFR2 rearrangements/fusions. Notably, the matured OS is longer than historical data; OS for responders was more than twice as long vs for non-responders. Clinical trial information: NCT02924376. [Table: see text]

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