Incidence of Type II Diabetes Mellitus and Hyperlipidemia in Patients Prescribed Dasatinib or Nilotinib As First or Second Line Therapy for Chronic Myelogenous Leukemia (CML)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4766-4766 ◽  
Author(s):  
Meg Franklin ◽  
Leah Burns ◽  
Samuel Perez ◽  
Deepak Yerragolam ◽  
Dinara Makenbaeva
Keyword(s):  
Incidence Rate ◽  
Index Date ◽  
Type Ii Diabetes Mellitus ◽  
Incidence Rates ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Baseline Characteristics ◽  
Concomitant Medications

Abstract Background: Metabolic changes such as Type II Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitor (TKI) therapy. Incidence of metabolic outcomes in this population has not been evaluated in large, real-world studies. The purpose of this study was to determine incidence and risk for T2DM and HLD in commercially and Medicare insured US patients prescribed dasatinib or nilotinib as first or second line therapy for CML. Methods: A retrospective cohort study using the MarketScan healthcare claims was conducted. Patients ≥18 years with ≥2 inpatient or outpatient claims for CML (ICD-9 205.10-205.12) separated by at least 30 days and ≥1 prescription for dasatinib or nilotinib from July 2006- December 2014 were eligible. Patients were required to have continuous enrollment for ≥6 months prior to the first TKI prescription (index date) and no exposure to a TKI other than imatinib during the pre-index period. No minimum follow-up time was required. First line TKI users were defined as those patients with no imatinib prescription during the pre-index period. Patients with a prescription for imatinib during the pre-index period were considered second line. Two cohorts of patients were studied. Cohort 1 was evaluated for the occurrence of T2DM, defined as ≥2 claims with an ICD-9 code for T2DM or 1 diagnosis claim and an anti-diabetic medication claim. Patients who had a diagnosis of T2DM or received medications for T2DM prior to the index date were excluded from cohort 1. Cohort 2 was evaluated for the occurrence of HLD, defined as ≥2 claims with an ICD-9 code for HLD, or 1 diagnosis claim and an anti-HLD medication claim. Patients with a diagnosis of HLD or medications for HLD prior to the index date were excluded from cohort 2. Patients were evaluated for the outcome of interest (T2DM or HLD) from index date until the outcome of interest occurred, discontinuation of therapy, switch in therapy, end of study (12/31/2014), or end of enrollment, whichever occurred first. To estimate the incidence rates of both outcomes of interest, person years were enumerated from index date until the end of follow up. Incidence rates were computed as the number of events divided by the sum of the person years (PY) at risk for all subjects in the cohort and were reported with associated 95% confidence interval (CI) assuming a Poisson distribution. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for outcomes while adjusting for age, gender, region, insurance type, index year, Charlson Comorbidity Index (CCI), comorbidities, concomitant medications, and line of therapy. Results: 2,004 patients met inclusion criteria for cohort 1 (n=1,272 dasatinib, n=732 nilotinib), while 1,280 patients met cohort 2 inclusion criteria (n=845 dasatinib, n=435 nilotinib). Baseline characteristics were largely similar between dasatinib and nilotinib patients in each cohort. Significant differences existed in index year, proportion of patients with certain comorbidities and baseline concomitant medications, and percentage of patients receiving the TKI for first line vs second line therapy. Among cohort 1, mean age was 53.4 years and 54.1% were male; median follow-up time was 216 days for dasatinib and 245 days for nilotinib. Incidence rate of T2DM was 17.58 per 1,000 PY (95% CI: 11.14, 26.38) for dasatinib, and 40.36 per 1,000 PY for nilotinib (95% CI: 27.60, 56.98). The HR for occurrence of T2DM (dasatinib as reference) was 2.77 (95% CI: 1.58, 4.86, P=0.0004), indicating patients on nilotinib had a 2.77 times greater risk of developing T2DM while adjusting for baseline characteristics. The mean age of cohort 2 was 48.6 years and 50.3% were male; median follow-up time was 213 days for dasatinib and 206 days for nilotinib. Incidence rate of HLD was 46.41 per 1,000 PY (95% CI: 33.00, 63.45) for dasatinib, and 74.63 per 1,000 PY for nilotinib (95% CI: 50.70, 105.94). The HR for occurrence of HLD (dasatinib as reference) was 1.75 (95% CI: 1.07, 2.87, P=0.025), indicating patients treated with nilotinib had a 1.75 times greater risk of developing HLD after adjusting for baseline characteristics. Conclusions: Patients receiving nilotinib for CML had a higher incidence rate and significantly greater adjusted risk for developing T2DM or HLD than patients receiving dasatinib. Disclosures Franklin: Bristol-Myers Squibb: Consultancy. Burns:Bristol-Myers Squibb: Employment, Equity Ownership. Perez:Bristol-Myers Squibb: Consultancy. Yerragolam:Bristol-Myers Squibb: Consultancy. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership.

Cytarabine plus mitoxantrone versus cytarabine plus clofarabine as second-line therapy in AML.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Zartash Gul ◽  
Asheesh Jain ◽  
Stacey A. Slone ◽  
Ali Raufi ◽  
Emily Marie Van Meter ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Overall Survival ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Baseline Characteristics ◽  
Bridging Strategy

e18001 Background: There are no comparative studies that can provide guidance about the choice of second line therapy in AML patients (pts). Methods: We retrospectively evaluated 30 consecutive pts who underwent reinduction chemotherapy for AML with mitoxantrone and cytarabine (ACM) or cytarabine and clofarabine (ACC). Results: Baseline characteristics of the pts are described in the Table. Ten pts achieved remission after initial induction therapy in ACM group and 4 pts in ACC group (P=0.71). Median length of remission was 314 days (d) (81-874 d) in ACM group and 178.5 d (57-232 d) in ACC group (P=0.13).After reinduction in ACM and ACC groups 9 and 3 patients achieved remission respectively (P=0.4).One pt in each group underwent allogeneic stem cell transplant. After a median follow-up of 11.2 m (ACM) and 10.5m (ACC), 9 and 6 pts had died in ACM and ACC groups respectively. Causes of death were progression (ACM=2pts, ACC= 1pt), end organ failure (3 pts each) and unknown (ACM=4pts, ACC=2 pts). Median Overall survival (OS) was 18.4 months (m) in ACM and 13.1 m in ACC group (P=0.49). After reinduction therapy OS was 8.3 and 6.9 m in ACM and ACC groups (P=0.72). In our patient cohort we did not find any baseline characteristics that were associated with OS or achievement of remission after reinduction therapy. Conclusions: In our pt cohort both ACM and ACC regimens demonstrated the ability to induce remission as a possible bridging strategy to allogeniec stem cell transplant. Larger studies are needed to compare these two regimens as well as evaluate any baseline characteristics which correlate with OS or achievement of remission. [Table: see text]

Comparison of Survival Rates, Healthcare Resource Use and Costs of Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2618-2618
Author(s):  
B. Douglas Smith ◽  
Jun Liu ◽  
Dominick Latremouille-Viau ◽  
Zhou Zhou ◽  
Annie Guerin ◽  
...  
Keyword(s):  
Research Funding ◽  
Index Date ◽  
Survival Rates ◽  
Baseline Period ◽  
Harvard University ◽  
Second Line ◽  
Second Line Therapy ◽  
Analysis Group ◽  
Line Therapy

Abstract Introduction: Dasatinib and nilotinib are two second-generation tyrosine kinase inhibitors (TKIs) that are well established as treatment options for patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase resistant or intolerant to imatinib and the treatment guidelines do not differentiate based on patient age. Importantly, elderly patients (≥65 years old) account for about half of CML patients; yet there are little data reported focusing on outcomes in this distinct group of patients, often with multiple medical problems and different socio-economic profiles when compared to younger patients. This study aimed to compare survival rates, healthcare resource utilization (HRU), and medical service costs between elderly CML patients receiving dasatinib versus nilotinib as second-line therapy after imatinib. Methods: Patients aged ≥65 years with ≥2 CML diagnoses who received imatinib as first-line therapy followed by nilotinib or dasatinib as second-line therapy were identified using the Medicare Research Identifiable Files (RIF) from 2006 to 2012. Selected patients were continuously enrolled in the Part A (i.e., institutional claims), Part B (i.e., non-institutional claims), and Part D (i.e., drug events) for ≥6 months before and ≥1 month after the second-line TKI therapy initiation date (i.e., index date). Patients enrolled in a clinical trial, those with a stem-cell transplant, or receiving chemotherapy (except hydroxyurea) during the 6 months before the index date (i.e., baseline period) were excluded from the study. Based on the second-line TKI, patients were classified as nilotinib users or dasatinib users. Survival rates were estimated using Kaplan Meir analyses and compared between nilotinib and dasatinib users using Cox proportional-hazards models. HRU and healthcare costs (USD 2013; payer’s perspective) were observed from the index date up to the end of follow-up. Because the length of follow-up varied across patients, HRU and costs were reported per-patient-per-month (PPPM). Incidence rate ratios (IRR) were estimated using Poisson regression models and monthly cost differences were estimated using general linear models with a log link and a gamma distribution or two-part models. Multivariate regression analyses were used to adjust for potential confounding factors measured during the baseline period or at the index date. Results: After applying the sample selection criteria, 659 patients using a second-line TKI therapy were selected; 280 were nilotinib users and 379 were dasatinib users. On average, patients had a follow-up of 24 months (median=22 months) after the index date. The mean age was 76 years and most patients were female (62%). Nilotinib and dasatinib users were generally similar in terms of gender, region of residence, prior imatinib treatment duration, CML complexity, and comorbidity profile. However, nilotinib users were slightly older than dasatinib users; a greater proportion of nilotinib users were 80+ years old at the index date (35% of nilotinib users vs. 27% of dasatinib users; p=.039). In addition, the proportion of patients with cardiovascular disease (40% of nilotinib users vs. 31% of dasatinib users; p=0.015) or congestive heart failure (23% of nilotinib users vs. 14% of dasatinib users; p=0.002) during the baseline period was higher in nilotinib users when compared to dasatinib users. Despite these differences, the median survival time was >4.9 years for nilotinib users and 4.0 years for dasatinib users (log rank test p=.032). After adjusting for potential confounding factors, nilotinib users had a mortality risk that was 38% lower than that of dasatinib users (p=.006) and, nilotinib users had 21% fewer inpatient admissions, 17% fewer inpatient days, 31% fewer emergency room visits, and 12% fewer outpatient visits when compared to dasatinib users (PPPM; all p≤.001). The adjusted monthly medical cost was $378 lower in nilotinib users when compared to dasatinib users (PPPM; p=.045). Conclusion: This retrospective study of elderly Medicare beneficiaries with CML receiving second-line therapy with dasatinib or nilotinib suggested that those receiving nilotinib had longer survival, lower HRU, and lower medical costs than those receiving dasatinib. Further health outcome researches and longer term studies focusing on elderly CML are needed to better define the best practice patterns. Disclosures Liu: Jun Liu is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Latremouille-Viau:Dominick Latremouille-Viau is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Zhou:Zhou Zhou is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Guerin:Annie Guerin is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Fernandez:Daniel Fernandez is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Yi:Dingdong Yi is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wang:Xufei Wang is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wu:Eric Q. Wu is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Mhatre:Novartis Pharmaceuticals Corporation: Employment. Keir:Novartis: Employment, Equity Ownership. Chen:Novartis: stock options Other; Novartis Pharmaceuticals Corporation: Employment.

scholarly journals Real-World Treatment Patterns and Outcomes Among Patients with Hairy Cell Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2125-2125
Author(s):  
Sudeep Karve ◽  
Victoria Divino ◽  
Andrew Gaughan ◽  
Mitch DeKoven ◽  
Guozhi Gao ◽  
...  
Keyword(s):  
Health Plan ◽  
Real World ◽  
Index Date ◽  
Treatment Patterns ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background and Objective : Hairy cell leukemia (HCL) is a rare condition and accounts for ~2% of all leukemia cases in the US. NCCN guidelines recommend first-line agents including pentostatin and cladribine among patients with HCL. However, a paucity of data exists with regard to real-world treatment patterns among patients with HCL. Current study evaluates treatment patterns and associated clinical outcomes among patients with HCL using a large US administrative claims database. Methods : This retrospective observational study was conducted using the IMS Health PharMetrics Plus Health Plan Claims Database (2006-2014), which includes over 150 million unique health plan members across the US and is nationally representative of the commercially-insured US population. Data includes date stamped medical and pharmacy records along with information on health plan enrollment. Individuals with at least 2 medical claims with a diagnosis for HCL (identified using ICD-9-CM cod: 202.4x) were selected and the first observed claim defined the "index date." Patients <18 years of age at index date or with other malignancies during 6 months (the "pre-index period") prior to index date were excluded. Patients were required at least 90 days of continuous enrollment (the variable "follow-up period") in the health plan post index date with exception of patients who died within 3 months of diagnosis. Patients were followed until death (recorded on inpatient discharge disposition), end of enrollment or end of database, whichever occurred earlier. Study measures including patient demographic and baseline clinical characteristics, line of therapy (LOT), treatment patterns, relapse (receipt of same or new regimen in subsequent LOT following a gap of 365 days) and refractory disease (receipt of same or new regimen where the gap of two adjacent LOTs was <365 days) and post-treatment complications were assessed during the follow-up period. All analyses were descriptive in nature. Results : The study cohort included 749 patients after applying the selection criteria (mean follow-up from diagnosis 32 months). At diagnosis, the mean age (standard deviation) of the study cohort was 56 (10) years and majority of patients were male (77%). Mean baseline comorbidity burden (assessed using Charlson Comorbidity Index score) was 0.8 (1.1) with hypertension (24%) and aplastic anemia (22%) being the two most common co-morbidities. Only 38% (n=282) of patients received first-line chemotherapy post diagnosis. Majority initiated first-line cladribine (76%) as a single agent, while 9% had evidence of single agent pentostatin. Mean time to initiation of first-line therapy from diagnosis was 132 (294) days and average time on first-line therapy was 34 (104) days. Among patients with first-line therapy 14% received second-line therapy and rituximab (53%) and cladribine (21%) were frequently observed second-line agents. Post first-line therapy, mean time to initiation of second-line therapy was 303 (406) days. Among second-line initiators, 76% had refractory disease and 24% had relapsed following first-line. Neutropenia and fever were frequently reported complications while on chemotherapy. Conclusion : The real-world chemotherapy utilization patterns observed in this study are consistent with the NCCN guidelines with cladribine and pentostatin being the agents of choice for first-line therapy. Following diagnosis, more than one-third of patients initiated chemotherapy and only a small proportion of these received second-line chemotherapy suggesting durable response with first-line therapy. Limited follow-up post first-line therapy may have impacted the proportion of patients initiating second-line therapy as well as categorization of refractory and relapse disease. Disclosures Karve: AstraZeneca: Employment. Divino:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gaughan:AstraZeneca: Employment. DeKoven:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gao:MedImmune: Employment. Lanasa:MedImmune: Employment.

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Efficacy of Cyclosporine Treatment in Patients with MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4608-4608
Author(s):  
Alina Kokhno ◽  
Elena Parovitchnikova ◽  
Elena Mikhailova ◽  
Yulia Olshanskaya ◽  
Irina Kaplanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stable Disease ◽  
Response Rate ◽  
Bone Marrow Failure ◽  
Normal Karyotype ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Myelodysplastic syndrome (MDS) represents a heterogenous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure and genetic instability. The recent clinical and laboratory investigations suggest that MDS is closely related to diseases in which the bone marrow failure is mediated at least in part by the immune system. The are few studies concerning the of efficacy of treatment of MDS pts with cyclosporine A (CSA) but they are limited to the group of pts with bone marrow hypoplasia. The aim of our study was to evaluate the efficacy of CSA treatment in MDS pts as first line or second line therapy. 48 pts with different forms of MDS were included in study. The group of first line CSA treatment included 30 pts, male-18/female-12, RA-3, RARS-1, RCMD-18, RAEB-7, RAEBt-1, 20-normal karyotype, 10-different abberations including: 5q−, 16q+, −7, 12q+, −Y, [11p+,7q−] and complex abb. Hypoplastic bone marrow was revealed in 15 pts, hyperplastic-8 pts, hypo/hyper-7 pts. Second line therapy group included 18 pts, male-9/female-9, RCMD-11, RARS-1, RAEB-5, RAEBt-1, normal karyotype-3, cytogenetic anomalies-13 (+8, 5q−,−7, +8 and complex abb.). Hypoplastic bone marrow was revealed in 12 pts, hyperplastic-4 pts, hypo/hyper-4 pts. The first line therapy consited of splenectomy in 8 pts, low doses of Ara-C-3, interferon-α-3, chemotherapy-2 and ATG-2 pts. CSA was applied at 5–10 mg/kg/day initially and then adjusted according to blood levels and toxicity. The maintenance dose was 1–3 mg/kg/day. Minimum time to response evaluation was one month. Complete response (CR) was defined as normal PB counts, BM aspirate; partial response-improvement of PB counts to 50% of normal and freedom from transfusions; stabilization-decrease of transfusion requirements and stabilization of PB counts for more then 1 month. Total response rate in first group was 60% (18 pts) with median follow up of 10 months (2–134). CR was estimated in 20% (6pts), median follow-up 72 months (44–134). 2 pts with CR are in clonal remission. 2 pts from response group developed acute leukemia (AL). 40% of pts showed no response.58% of pts without response developed RAEB or AL. 42% of pts were in stable disease and were treated with another modalities. The response rate in second group was 61% (11 pts) with median follow-up of 7 months (1–78). 22% (4 pts) achieved CR, median follow-up 60 months (43–78). 39% of pts showed no response. 71% from these pts (5) transformed to RAEB or AL. 2 pts remained in stable disease. In both groups response was registrated from 1 to 4 months from treatment initiation (median 3 months). CR was achieved in the majority of pts after 1 year of treatment. Response was achieved in 77% of pts with hypo/hyper and hypoplastic bone marrow and in 12% of pts with hyperplastic bone marrow. Overall survival was decreased in pts with more the 5% blasts in bone marrow (p=0,02 for 1st line group, p=0,075 for 2nd line group), and increased for pts with hypo and hypo/hyper bone marrow cellularity (p=0,002 for 1st line group). There was no impact of cytogenetics. We may conclude, that CSA demonstrates good efficacy in therapy of MDS pts, especially for pts with RA, RARS and RCMD with hypo and hypo/hypercellular bone marrow and reactive lymphoid nodules in bone marrow. It can be initiated as 1st or 2nd line therapy and should be continued at least for 3 months before evaluating of response.

Splenectomy Is Still a Valid Option For Splenic Marginal Zone Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5129-5129
Author(s):  
Alessandro Pulsoni ◽  
Pasqualina D'Urso ◽  
Gianna Maria D'Elia ◽  
Giorgia Annechini ◽  
Caterina Stefanizzi ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Spleen Size ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma characterized by splenomegaly, frequent moderate lymphocytosis with or without villous morphology and possible involvement of various organs, especially the bone marrow (BM). Diagnosis is classically based on the spleen histology, but it can be made on the BM biopsy, based on the typical intrasinusoidal cell infiltration pattern and immunohistochemistry. Different therapeutic options are available, but to date there are no conclusive comparative data. Patients and methods We retrospectively analyzed 83 consecutive patients with a diagnosis of SMZL observed at our Institution between 1999 and 2013. The diagnosis was based on the BM biopsy in 79 patients; the BM was negative in 4 patients. Diagnosis was histologically confirmed on the spleen in 27 patients who underwent splenectomy. Patients presented a median age of 72.5 years (range 38-84); 43 were males. The median spleen size at diagnosis was 145 mm, ranging from 100 to 300 mm. The majority of patients were stage IV at diagnosis for BM infiltration (95%); B symptoms were present in 4 of them (4.8%). Forty-two patients (50.6%) had a lymphocytosis at diagnosis and 13 (15.6%) presented an IPI score higher than 3. Thirty-five of them (42%) had a MZL BM infiltration superior to 30% of the total bone cellularity. Forty-two patients (50.6%) underwent a watch and wait policy (WW), while 41 (49.4%) were treated within 6 months from diagnosis, mainly because of symptomatic splenomegaly; in these patients, treatment consisted of splenectomy, chemotherapy or chemotherapy plus immunotherapy with Rituximab. The features of patients submitted to WW with respect to patients treated at diagnosis were comparable for the various parameters mentioned above, except for spleen size (higher in patients treated at presentation) and lymphocyte count (higher in patients who were observed). After a median follow-up of 64 months, the overall median survival was 96%. Among the 42 WW patients, 18 (42.8%) are still untreated after a median follow-up of 57.5 months, while 24 (57.2%) have required therapy; the median treatment-free interval in these patients was 25.5 months. Concerning the 41 patients who underwent treatment at diagnosis, after a median follow-up of 50 months, 13 (31.7%) have required a subsequent second-line treatment. The interval between first-line approach and re-treatment in patients treated at diagnosis was 30 months. Overall, 27 patients were treated with splenectomy only (either at diagnosis or after a WW period): only 6 of them (22%) had a subsequent progression after a median latency of 42 months; 26 were treated with chemotherapy alone (alkylating agents in the majority of them, combination therapy in a minority): 15 of them (60%) had a subsequent relapse or progression after a median of 9 months; 12 patients received a Rituximab-containing regimen: of these, only 2 (16%) have so far required a second-line therapy after 10 and 26 months respectively. Conclusions The WW policy is a valid option for asymptomatic patients: in these patients, after 4.5 years from diagnosis more than 40% is still untreated. In patients requiring treatment, splenectomy alone is followed in the majority of patients by a long period of good disease control: only 22% required a second-line therapy after 3.5 years. The addiction of Rituximab to chemotherapy seems to reduce the probability of relapse and to prolong the response duration. However, these preliminary data need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.

Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nizar M. Tannir ◽  
Robert J. Motzer ◽  
Elizabeth R. Plimack ◽  
David F. McDermott ◽  
Philippe Barthelemy ◽  
...  
Keyword(s):  
Risk Groups ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Post Hoc ◽  
Study Dose ◽  
Clinical Trial Information

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]

scholarly journals Efficacy and Safety of Ruxolitinib in the Treatment of Elderly Patients with Policythemia Vera Resistant/Intolerant to Hydroxyurea

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2581-2581
Author(s):  
Roberto Latagliata ◽  
Daniela Bartoletti ◽  
Alessandro Andriani ◽  
Massimo Breccia ◽  
Elena Rossi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Age Groups ◽  
Second Line ◽  
Efficacy And Safety ◽  
Second Line Therapy ◽  
Advisory Committees ◽  
Line Therapy ◽  
Dose Reductions

Abstract Introduction: Ruxolitinib (Rux) has been recently approved as second-line therapy in patients (pts) with Polycythemia Vera (PV) resistant/intolerant to hydroxyurea (HU). Median age of PV pts enrolled in the pivotal Response trials was around 60 yrs; at present, no data is reported on the use of Rux in elderly pts. Aims: In a real-world cohort of PV pts treated with Rux, we investigated whether the efficacy and safety of Rux were comparable in pts who initiated therapy when aged ≥75 years compared with younger pts. Methods: After IRB approval, clinical/laboratory data of 934 WHO2016-defined PV pts followed in 29 Hematology Centers were retrospectively collected. Of them, 168 (17.9%) were considered resistant/intolerant to HU at any time during follow-up by responsible physician and shifted to Rux as second-line therapy. Results: Among the 168 pts treated with Rux, 42 (25%, median age 78.2 years) were aged ≥75 yrs at Rux start, 74 (44%, median age 67.7) were aged 60-74 and 52 (31%, median age 53) were &lt;60 at Rux start. No significant differences were observed between the 3 groups, apart from a lower need for phlebotomies in pts aged ≥75 yrs and lower presence of palpable spleen in older pts (age ≥60), that more frequently switched to Rux due to HU intolerance (Table 1). Median duration of HU treatment was 41.0 months (IQR 14.6 - 85.8), with a trend for a longer median treatment duration in pts aged ≥75 [61.0 months (IQR 21.5 - 89.6) vs 35.9 months (IQR 13.4 - 79.6), p=0.04]. Rux starting dose was similar across age groups; however, more elderly pts underwent Rux dose reductions during follow-up (45.2% in pts aged ≥75 vs 28.6% in younger pts, p=0.04). Responses during Rux therapy are reported in Table 2, with no significant differences between the 3 groups at any time. In the overall cohort, response on PV-related symptoms at 6 and 12 months was significantly higher in pts who switched to Rux because of HU intolerance; however, this difference was not observed in pts aged ≥75 yrs. As to the most common hematologic Rux-related toxicities, grade 3-4 anemia and thrombocytopenia were observed in only 2 (1.2%) and 5 (3%) pts, with no difference across age groups (p=0.45 and p=0.18). However, any grade anemia and thrombocytopenia during Rux were more frequently observed in pts aged ≥75 (68.3% vs 51.7% of anemia, p=0.06 and 12.2% vs 3.5% of thrombocytopenia in younger pts, p=0.04). Nineteen and 4 pts experienced infectious and thrombotic complications during Rux with incidence rates of 0.59 and 0.12 per 100 patient-months, respectively, comparably in younger and older (≥75) pts (p=0.75 and p=0.29, respectively). Notably, 6 infections were herpes simplex/zoster virus, comparably distributed between the 3 groups (p=0.60). Permanent Rux discontinuation was needed in 14 pts (8.3%) after a median Rux exposure of 7.8 months (IQR 4.6 - 17.6) (incidence: 0.41 per 100 pts/months). Discontinuation was comparable between age groups, with Rux stop in 4 pts aged ≥75 yrs and 10 younger pts (2.4% vs 5.2% at 8 months, log-rank p=0.75). At last follow-up, 2 pts had died (1 from 2 nd neoplasia after 19.1 months from Rux start and 1 from acute leukemia after 3.3 years), both pts aged 60-74 yrs. Conclusions. In this real-world analysis, use of Rux in HU resistant/intolerant elderly PV pts was effective and safe despite the more frequent need for dose reductions. Older age should not discourage Rux therapy, but stricter hematological monitoring may be suggested. Figure 1 Figure 1. Disclosures Latagliata: BMS Cellgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria; Novartis: Honoraria. Bonifacio: Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Cavo: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palandri: AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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