scholarly journals Second-Line Therapy for Immune Thrombocytopenia: Real-World Experience in Canada

2020 ◽  
Vol 15 (4) ◽  
pp. 28-35
Author(s):  
Hasmik Nazaryan ◽  
Yang Liu ◽  
Emily Sirotich ◽  
Joanne Duncan ◽  
Ishac Nazy ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Second Line ◽  
Treatment Sequence ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Thrombopoietin Receptor ◽  
Count Response ◽  
Immunosuppressant Medications ◽  
Étude De Cohorte

BackgroundThe sequence of second-line therapy used for the treatment of immune thrombocytopenia (ITP) is variable. This study aimed to describe the types and sequences of second-line therapies for a large cohort of ITP patients in Canada. MethodsWe completed a retrospective cohort study of the McMaster ITP Registry. We included patients with primary or secondary ITP who had received one or more second-line therapies including any of the splenectomy, rituximab, danazol, dapsone, or thrombopoietin receptor agonists (TPO-RAs), or immunosuppressant medications. Immunosuppressant medications included azathioprine, cyclophosphamide, cyclosporine, or mycophenolate given alone or in combination. ResultsWe identified 204 ITP patients who had received one or more second-line therapies. The most common second-line therapies were immunosuppressant medications (n = 106; 52.0%), splenectomy (n = 106; 52.0%), TPO-RAs (n = 75; 36.8%), danazol (n = 73; 35.8%), and rituximab (n = 67; 32.8%). For patients who received only one second-line therapy (n = 88), the most common treatment was splenectomy (n = 28; 31.8%). For patients who received more than one second-line therapy (n = 116), the most common treatment sequence was splenectomy, followed by immunosuppressant medications (n = 7; 6.0%). Of the 154 evaluable patients at the end of follow-up, 69 (44.8%) achieved a complete platelet count response and 101 (65.5%) achieved a partial response. ConclusionImmunosuppressant medications and splenectomy are commonly used as second-line therapies for ITP in Canada. Treatment choices and the sequence of treatments were variable. RESUME Contexte La séquence de la thérapie de deuxième ligne utilisée pour le traitement de la thrombocytopénie immunitaire (PTI) est variable. Cette étude visait à décrire les types et les séquences des thérapies de deuxième ligne pour une large cohorte de patients atteints de PTI au Canada. MéthodesNous avons réalisé une étude de cohorte rétrospective du registre ITP de McMaster. Nous avons inclus des patients atteints de PTI primaire ou secondaire qui avaient reçu une ou plusieurs thérapies de deuxième ligne, y compris une splénectomie, du rituximab, du danazol, de la dapsone ou des agonistes des récepteurs de la thrombopoïétine (AR-TPO), ou des médicaments immunosuppresseurs. Les médicaments immunosuppresseurs comprennent l’azathioprine, le cyclophosphamide, la cyclosporine ou le mycophénolate, administrés seuls ou en combinaison. RésultatsNous avons identifié 204 patients atteints de PTI qui avaient reçu une ou plusieurs thérapies de seconde ligne. Les thérapies de deuxième ligne les plus courantes étaient les immunosuppresseurs (n = 106; 52.0%), la splénectomie (n = 106; 52.0%), les AR-TPO (n = 75; 36.8%), le danazol (n = 73; 35.8%) et le rituximab (n = 67; 32.8%). Pour les patients qui n’ont reçu qu’un seul traitement de deuxième intention (n = 88), le traitement le plus courant était la splénectomie (n = 28; 31.8%). Pour les patients qui ont reçu plus d’un traitement de deuxième ligne (n = 116), la séquence de traitement la plus courante était la splénectomie, suivie par les médicaments immunosuppresseurs (n = 7; 6.0%). Sur les 154 patients évaluables à la fin du suivi, 69 (44.8%) ont obtenu une réponse complète de la numération plaquettaire et 101 (65.5%) une réponse partielle. ConclusionLes médicaments immunosuppresseurs et la splénectomie sont couramment utilisés comme traitements de deuxième intention pour le PTI au Canada. Les choix de traitement et la séquence des traitements sont variables.

Thrombopoietin receptor agonists as second-line therapy in splenectomy-eligible persistent immune thrombocytopenia

2019 ◽  
Vol 30 (6) ◽  
pp. 295-299 ◽  
Author(s):  
Fabrizio Vianello ◽  
Fabio D’Amore ◽  
Anna M. Lombardi ◽  
Ilaria Caputo ◽  
Alberto Friziero ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Second Line ◽  
Second Line Therapy ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Line Therapy ◽  
Thrombopoietin Receptor

scholarly journals Second-Line Therapy for Immune Thrombocytopenia: Real-World Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2120-2120
Author(s):  
Hasmik Nazaryan ◽  
Yang Liu ◽  
Emily Sirotich ◽  
Joanne M Duncan ◽  
Donald M. Arnold
Keyword(s):  
Real World ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Therapy ◽  
Start Date ◽  
Line Therapy ◽  
Treatment Start

Background: Immune Thrombocytopenia (ITP) is an autoimmune platelet disorder that can lead to serious morbidity caused by bleeding and therapy-associated toxicities. The sequence of first-line therapies is well-defined, but the sequence of second-line therapies lacks consensus. A description of real-world experience is necessary to understand practice patterns with respect to second-line therapies and identify gaps in care. The objective of this study was to describe the types and chronological sequences of second-line therapies in a large cohort of ITP patients. Methods: This was a retrospective cohort study. The population was derived from the McMaster ITP Registry, a prospective longitudinal registry of patients presenting with thrombocytopenia (platelets <150 × 109/L) to an academic hematology clinic in Hamilton, Canada. Inclusion criteria were: 1) diagnosis of primary or secondary ITP at most recent follow-up; 2) received one or more second-line therapy since initial ITP diagnosis; and 3) ≥6 months of follow up. No exclusions were applied. The sequence of second-line therapies was determined by treatment start dates. For treatments that were administered before enrollment in the registry, the order of treatment was determined by the reported treatment start date. When the start date was not reported, the sequence of treatments was assumed to be the order in which they were mentioned in the medical records. Second-line therapies included: splenectomy; rituximab; danazol; dapsone; thrombopoietin receptor agonists (TPO-RAs): eltrombopag or romiplostim; and immunosuppressants: mycophenolate, cyclosporine, azathioprine or cyclophosphamide. Results: From January 2010 to December 2017, 789 patients with thrombocytopenia were registered in the McMaster ITP Registry. Of those, 204 had ITP and received second-line therapy (57.4% female). Median duration of ITP from the initial presentation to the most recent diagnosis was 9 years (IQR, 4-19). The proportion of patients who received each type of second-line therapy at any time were immunosuppressants (n=106, 52.0%), splenectomy (n=106, 52.0%), TPO-RAs (n=75, 36.8%), danazol (n=73, 35.8%), rituximab (n=67, 32.8%), and dapsone (n=4, 2.0%). Overall, 69 unique treatment sequences were identified. For patients who received one second-line treatment only (n=88), the most common single treatment was splenectomy (n=28, 31.8%), followed by immunosuppressants (n=21, 23.9%) and danazol (n=18, 20.5%) (Figure 1). For patients who received more than one second-line therapy (n=116), the most common treatment sequences were splenectomy followed by immunosuppressants (n=7, 6.0%); immunosuppressants followed by rituximab (n=6, 5.0%), and immunosuppressants followed by danazol (n=5, 4.0%). In patients who received each of these therapies, the last second-line treatments received were TPO-RAs (52/75, 69.3%), immunosuppressants (45/106, 42.5%), rituximab (37/67, 55.2%), splenectomy (36/106, 33.9%), danazol (33/73, 45.2%), and dapsone (1/4, 25%). Conclusion: The types and sequences of second-line therapies for ITP were variable in a large Canadian academic center, where access to certain treatments including TPO-RAs and rituximab is limited. In this setting, splenectomy and immunosuppressant medications were commonly used as early second-line therapies. TPO-RAs were most often the last second-line treatment in the sequence of therapies used. Drug accessibility and other factors related to the choice of second-line therapies require further evaluation. Disclosures Arnold: Bristol-Myers Squibb: Research Funding; Principia: Consultancy; Rigel: Consultancy, Research Funding; Novartis: Honoraria, Research Funding.

scholarly journals Impact of Treatment Sequencing on Outcomes and Costs in Relapsed Follicular or Other Low Grade B-Cell Non-Hodgkin Lymphoma - Results of an Evidence-Based Budget Impact Model

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky
Keyword(s):  
Follicular Lymphoma ◽  
Low Grade ◽  
Second Line ◽  
Treatment Sequence ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Duration Of Response ◽  
Budget Impact Model

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.

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.

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