scholarly journals Updated Perspectives on the Management of Relapsed and Refractory Multiple Myeloma

2021 ◽  
Vol 44 (12) ◽  
pp. 682-689
Author(s):  
Linda Heimberg ◽  
Stefan Knop
Keyword(s):  
Treatment Options ◽  
Next Generation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Early Phase Trials ◽  
Choice Of Treatment ◽  
Immunomodulatory Drug ◽  
To Come ◽  
Third Line ◽  
Current Guidelines

<b><i>Background:</i></b> With the availability of T-cell-directed therapy and next-generation compounds of established classes of drugs, the treatment of relapsed/refractory (r/r) myeloma is getting more complex. However, treatment options in practice are limited by availability, approval, and patient comorbidity. The aim of this article is to provide a practical approach toward the choice of treatment for r/r myeloma patients. <b><i>Summary:</i></b> Regarding market authorization and current guidelines, at least in Germany, most patients nowadays will have received a doublet or triplet combination as first-line therapy containing a proteasome inhibitor and an immunomodulatory drug, mostly lenalidomide. We focus on the treatment options for patients that are ineligible for (another) stem cell transplantation. We will review treatment options for relapse after first- or second-line therapy and beyond third-line. <b><i>Key Messages:</i></b> There is promising data supporting the efficacy and safety of triplet combinations containing anti-CD38-monoclonal antibodies (anti-CD38 mAbs) at first or second relapse in combination with next-generation compounds. For the treatment beyond third-line, comparative studies are scarce but some promising compounds are available via conditional authorization, and there is more to come in the future. We will present some early phase trials featuring promising results.

scholarly journals Systematic Literature Review on Global Real-World Treatment Patterns of Mantle Cell Lymphoma (MCL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5881-5881
Author(s):  
Keri Keri Yang ◽  
Beth Lesher ◽  
Eleanor Lucas ◽  
Tony Caver ◽  
Boxiong Tang
Keyword(s):  
Literature Review ◽  
Adverse Events ◽  
Real World ◽  
Treatment Options ◽  
Treatment Patterns ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line

Introduction: MCL is an aggressive type of non-Hodgkin's lymphoma, and was reported associated with early relapse and poor long-term survival. Treatment options include chemotherapy, immunotherapy, and molecular targeted therapies. As of 2019, molecular targeted therapies available in the United States indicated for the treatment of MCL include the proteasome inhibitor bortezomib, the immunomodulatory drug lenalidomide (following two previous lines of therapy), and the Burton's tyrosine kinase inhibitors (BTKIs) ibrutinib and acalabrutinib (following at least one previous line of therapy). Objective/Methods: To examine the real-world treatment patterns of patients with MCL globally, a systematic literature review was performed (2010-2019) with predefined methodology and inclusion and exclusion criteria. Embase and Medline were searched via ProQuest and the Cochrane Controlled Register of Trials (CENTRAL) via the Cochrane Library. Results: Of the 2207 publications identified, 6 publications (US, n = 4; EU, n = 2) provided information on the first-line treatment of MCL (Table). The most commonly administered first-line treatments were bendamustine-rituximab; high dose cytarabine ± rituximab; and cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) ± rituximab although differences were noted across studies. Most patients received rituximab first-line either in combination with chemotherapy (54.2%-87.5%) or as monotherapy (12.9%-28.9%); although in some studies, rituximab maintenance therapy could not be excluded. The most commonly administered second-line therapies were cytarabine, rituximab monotherapy, and ibrutinib while third-line therapies were rituximab monotherapy, ibrutinib, and temsirolimus. Nine studies provided data on the real-world treatment of MCL with the BTKI ibrutinib (EU, n = 3; US, n = 5; EU/US, n = 1; Table); no real-world studies were identified for acalabrutinib. Six studies enrolled patients only with relapsed or remitting MCL; 3 studies enrolled patients (≤7.5%) who received ibrutinib as first-line therapy. Ibrutinib second-line therapy was administered to 13%-20% of patients and third-line therapy to 21% of patients. Ibrutinib discontinuation rates in 7 studies varied from 38.7%-83.6%. Non-response, including relapse or progression (34.6%-100%), was the main cause of discontinuation, followed by toxicity/adverse events (8.1%-25.6%). Across studies, toxicity/adverse events causing ibrutinib discontinuation included atrial fibrillation, bleeding/hemorrhage, chronic obstructive pulmonary disease, diarrhea, herpes zoster, infection, leukocytosis/ lymphocytosis, lung cancer, myelodysplastic syndrome, and thrombocytopenia. Two studies provided information on ibrutinib dose reductions (16.4% of patients) and ibrutinib dose interruptions (7.8%-30.2% of patients). Treatment options administered post-ibrutinib included rituximab (52.7%), hyper-CVAD + rituximab (16.7%-25.8%), lenalidomide-based regimens (9.7%-41.5%), and bortezomib-based regimens (8.4%-34.4%). Conclusion: Our analyses showed that most patients with MCL received first-line chemoimmunotherapy, although regimens varied across studies. Approximately 13%-21% of patients received ibrutinib following first-line therapy. Most ibrutinib discontinuation was due to progression followed by toxicity/adverse events. Upon discontinuation of ibrutinib, considerable variation in treatments was seen and no standard therapy identified. Given the limitations of current therapies, there is a need for additional second- and third-line treatments for patients with MCL. Quantitative assessments of clinical endpoints from real-world studies evaluating BTKI therapies are also warranted. Disclosures Yang: BeiGene, Ltd.: Employment. Lesher:Pharmerit: Employment. Lucas:Pharmerit: Employment. Caver:BeiGene, Ltd.: Employment. Tang:BeiGene, Ltd.: Employment.

Ipertiroidismo e tiroidite autoimmune in età evolutiva

2021 ◽  
Vol 40 (10) ◽  
pp. 637-645
Author(s):  
Maria Chiara Pellegrin ◽  
Alessandro Occhipinti ◽  
Benedetta Bossini ◽  
Stefania Norbedo ◽  
Elena faleschini ◽  
...  
Keyword(s):  
Remission Rate ◽  
Treatment Options ◽  
Spontaneous Remission ◽  
Antithyroid Drugs ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Antithyroid Treatment ◽  
Paediatric Age ◽  
Optimal Regimen

Hyperthyroidism is a rare clinical entity in paediatric age. In most cases the etiology is autoimmune and goiter represents the typical presentation. Ophthalmopathy is rare and can precede the diagnosis of autoimmune hyperthyroidism. Thyrotoxicosis caused by the hyperthyroid phase of Hashimoto’s thyroiditis must be carefully distinguished from Graves’ disease (GD), since the first condition has a better prognosis for spontaneous remission. Three treatment options are currently available for the management of paediatric GD. First-line therapy is antithyroid drugs, while thyroidectomy and radioiodine are considered on relapse. A lower remission rate and a higher risk of adverse events are observed after the first course of methimazole in childhood with respect to adulthood. Children and adolescents may require a prolonged antithyroid treatment, but an overall consensus regarding the optimal regimen is lacking.

Cisplatin as first-line therapy for metastatic breast cancer.

1988 ◽  
Vol 6 (12) ◽  
pp. 1811-1814 ◽  
Author(s):  
G W Sledge ◽  
P J Loehrer ◽  
B J Roth ◽  
L H Einhorn
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
The United States ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Ii Studies ◽  
Third Line

Cisplatin has had only minimal activity when used as second- and third-line chemotherapy for metastatic breast cancer (MBC). There have been no phase II studies in the United States evaluating cisplatin in patients with MBC with no prior chemotherapy. We therefore treated 20 consecutive patients with cisplatin 30 mg/m2/d for four days every 3 weeks for a maximum of six courses. We obtained partial responses in nine of 19 evaluable patients (47%), with responses in liver, lung, and soft tissue indicator lesions. Our data suggest that cisplatin has substantial single-agent activity as front-line therapy in MBC, and should be considered for inclusion in first-line combination chemotherapy regimens.

scholarly journals Lenalidomide in follicular lymphoma

Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2133-2136 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Nathan H. Fowler
Keyword(s):  
United States ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
The United States ◽  
First Line ◽  
Safety And Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immunomodulatory Drug

Abstract Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.

Systemic Mastocytosis. A GIMEMA Multicenter Survey.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4874-4874
Author(s):  
Livio Pagano ◽  
Caterina Giovanna Valentini ◽  
Pellegrino Musto ◽  
Morena Caira ◽  
Michela Rondoni ◽  
...  
Keyword(s):  
Mast Cell ◽  
Point Mutation ◽  
Systemic Mastocytosis ◽  
Response To Treatment ◽  
First Line ◽  
Kit Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multicenter Survey ◽  
Third Line

Abstract To evaluate clinical and biological features, treatments and outcome of patients(pts) with Systemic Mastocytosis(SM). A retrospective study (1995–2006) about pts with SM admitted in 14 Italian hematology divisions in tertiary cares or university hospitals. 30 cases of SM were collected(median age 62 y.o.; M/F 14/16) and classified according to the WHO criteria: Mast Cell Leukemia in 14 pts, Aggressive SM in 12 and Indolent in 3; the remaining one had SM with associated clonal non-mast cell-lineage hematologic disease. Skin was the principal extramedullary organ involved (19 pts) followed by spleen(15), liver(13), and cardiovascular system(12). Molecular biology studies were performed in 22 pts: 15 showed the c-kit point mutation D816V; in another patient a different c-kit mutation was found while in 3 pts additional gene defects and karyotype abnormalities were recognized. Treatments were heterogeneous, and the same patient could have received different therapies after failure of the previous one. Imatinib(400 mg/day) was used in 17 pts (11 as first line therapy, 5 and 1 as second and third line respectively); interferon-alpha(3×3 MU s.c. weekly) was employed in 7 patients(4 as first line therapy, 2 as second and 1 as third line); 2-CDA(0.14 mg/kg) was administered in 3 pts(1 as first, 1 as second and 1 as third line therapy); 2 patients underwent HSCT as second and third line respectively. Data about response to treatment are reported in the table. The overall response rate to imatinib was of 30%, registering 1 complete remission(CR) and 4 partial remissions. All but one responsive patients did not present c-kit point mutation. Three pts(10%) died for progression of SM; a fourth patient in CR died for accidental causes. The actuarial Kaplan-Meier curve at 10 years showed an overall-survival of 87%. Conclusions: SM is a rare disease, characterized by severe and life-threatening mediator-related symptoms but with a low mortality rate. D816V c-kit mutation is frequent and associated with resistance against imatinib: only 1 patient showed a CR. Of note 2-CDA has shown interesting clinical response: all 3 treated pts showed a clinical improvement. Because of the rarity of SM, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies; it is possible that new tyrosine kinase inhibitors could allow to achieve clinical and molecular remission of disease, crossing resistence to imatinib due to c-kit mutation, in order to improve above all quoad valitudinem prognosis of these pts. Response to treatments. DRUGS CR PR Stable Unrespons. N.E. TOTAL Imatinib 1 4 5 3 4 17 INF-alpha 0 1 1 5 0 7 2-CDA 0 3 0 0 0 3 Conventional CTX 0 1 2 4 1 8 Allo-HSCT 2 0 0 0 0 2 Wait & Watch 0 0 6 2 0 8

Activity and safety of third-line BRAF-targeted therapy (TT) following first-line TT and second-line immunotherapy (IT) in advanced melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10049-10049
Author(s):  
Victoria Atkinson ◽  
Kathleen Batty ◽  
Georgina V. Long ◽  
Matteo S. Carlino ◽  
Geoffrey David Peters ◽  
...  
Keyword(s):  
Median Duration ◽  
Progressive Disease ◽  
Treatment Options ◽  
Mek Inhibitor ◽  
Advanced Melanoma ◽  
Braf V600e ◽  
Second Line ◽  
Line Therapy ◽  
Third Line ◽  
Switch Group

10049 Background: Patients with advanced melanoma who progress on 1st line TT and 2nd line IT have limited treatment options. We explored the safety and efficacy of re-treatment with 3rd line TT. Methods: was pooled from 6 centers in Australia from 2009-2018. Eligible patients with BRAF V600 mutant melanoma had 1st line therapy with a BRAF/MEK inhibitor, 2nd line IO and were re-challenged with a BRAF/MEK inhibitor. Results: 90 patients were included; median age 61 years, 78% BRAF V600E, 89% ECOG 0-1 at baseline. 1st line TT was combination BRAF/MEK inhibitors in 80%, predominately dabrafenib/trametinib. Response to 1st line therapy was CR 20%, PR 41%, SD 17% and PD 13% and median duration of therapy was 7.2 months (0-33 months). 70% stopped for progressive disease, 9% toxicity and 16% had a planned switch to immunotherapy. For 2nd line IT, 49% had PD-1 alone, 33% had PD-1+CTLA-4, 14% had CTLA-4 alone. Only median duration on IT was 67 days (0-23 months), 81% ceased for PD, 14% for toxicity. Of patients who had a planned switch to IO before 1st line TT progression, one patient responded to second line IO with SD as BORR, there were no other responses to 2nd line IO in the planned switch group. At 3rd line TT re-challenge, 54% were AJCC stage IVd, 34% IVc, 51% had elevated LDH, 59% ECOG 0-1. 47% were re-challenged with dabrafenib/trametinib, 33% vemurafenib/cobimetinib, 11% encorafenib/binimetinib. BORR was 28%, with median duration on 3rd line TT 81 days. The OS was 1.7 years, with 34% alive at time of analysis. Conclusions: Despite progression on 1st line TT and 2nd line IT, patients may experience meaningful response and on re-challenge TT.

scholarly journals Outcomes of Plasma Cell Leukemia Patients in the Era of Next-Generation Novel Agents: A Single-Center Retrospective Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Alex Ge ◽  
Chiung-Yu Huang ◽  
Thomas Martin ◽  
Jeffrey L. Wolf ◽  
Nina Shah ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Next Generation ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Introduction Primary plasma cell leukemia (pPCL) is a rare and aggressive disease comprising 1-5% of all plasma cell dyscrasias. Although historically pPCL has been defined by circulating plasma cells (CPCs) ≥ 20% and 2.0 × 109/L, many series require only one of these two criteria for diagnosis. Over time there has been a pressing need to change the definition further in order to capture patients at an earlier stage of the disease. Recent studies have shown that multiple myeloma (MM) patients who have CPCs ≥ 5% but &lt; 20% at diagnosis have similarly poor outcomes. These thresholds for defining pPCL have not been studied in the current era of novel agents. While bortezomib-based regimens have been shown to extend pPCL patient survival, studies with next-generation agents such as carfilzomib (CFZ), pomalidomide, and daratumumab (DARA) are still scarce. Methods We performed a single-center, retrospective study of patients who at diagnosis had pPCL (defined as CPCs ≥ 20% or 2.0 × 109/L) or had MM with &lt; 20% CPCs (MM-CPC). Patients were treated at our institution between 1/1/2000-7/17/2020. Overall response rates were determined according to International Myeloma Working Group criteria. Overall survival (OS) was defined as the length of time between initiation of first line therapy and death. Progression-free survival (PFS) was defined as the length of time between initiation of first line therapy and first progression. OS and PFS were compared using log-rank tests. Results Of the 54 patients identified, 38 had pPCL and 16 had MM-CPC. The median age at diagnosis of the pPCL and MM-CPC groups were 59.2 (range 43-94) and 59.8 years (range 29-79), respectively, with a similar percentage of females, 47.4% vs. 37.5%. Both groups were similarly distributed by year of diagnosis; 76.3% and 62.5% of pPCL and MM-CPC patients were diagnosed between 2012-2020, respectively. The pPCL cohort had median CPCs of 40% (15-98) while the MM-CPC cohort had median CPCs of 4% (1-15). Median CPCs at diagnosis was 3.36 (0.44-179) × 109/L in the pPCL group compared to 0.33 (0.04-1.79) × 109/L in the MM-CPC group. Most patients for both groups were ISS stage III at diagnosis (57.9% in pPCL cohort, 56.2% in MM-CPC cohort). R-ISS assessment was not feasible due to missing data. A greater proportion of patients in the pPCL group (44.7%) had complex cytogenetics at diagnosis compared to the MM-CPC group (25.0%). All patients were exposed to at least one novel agent over the entire disease course. Of these patients, 50 (92.6%) were exposed to bortezomib, 45 (83.3%) to lenalidomide, 33 (61.1%) to CFZ, 22 (40.7%) to DARA, 13 (24.1%) to pomalidomide, and 4 (7.4%) to venetoclax. Twenty-four patients (44.4%) received an autologous stem cell transplant (ASCT). At the best response to treatment, 76.7%, 62.8% and 37.9% of patients achieved a partial response or greater to first, second and third line therapy, respectively. The median OS of the pPCL and MM-CPC groups was 34.5 and 35.5 months (p = 0.97) (Figure 1A), while the median PFS was 13.9 and 10.9 months (p = 0.52) (Figure 1B), respectively. The median follow-up was 28.1 months. No differences were observed for patients with CPCs &lt; 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs &lt; 2 × 109/L compared to CPCs ≥ 2 × 109/L (p = 0.35). Since we did not observe any meaningful difference in OS or PFS between the pPCL and MM-CPC groups, we combined these groups for further survival analysis. Patients exposed to either DARA or CFZ (n = 37) had a median OS of 59.2 months, while patients exposed to neither drug (n = 17) had a median OS of 11.7 months (p = 0.02) (Figure 1C). ASCT was associated with a prolonged median OS (66.8 months vs. 17.2 months, p = 0.0001) (Figure 1D), while a complex karyotype at diagnosis was associated with a poorer median OS (17.4 months vs. 66.8 months, p = 0.01). Conclusions In the era of next-generation novel agents, overall and progression-free survival of pPCL and MM-CPC patients are similar. Patients exposed to DARA or CFZ have an improved survival compared to those who did not receive these drugs. ASCT is also associated with a superior survival over those who did not receive a transplant. Further studies are needed to evaluate the efficacy of these next-generation drugs in this patient population. Disclosures Martin: Janssen: Research Funding; Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Roche: Research Funding; Janssen: Research Funding; Amgen: Consultancy; GSK: Research Funding; Bristol Myers Squibb: Research Funding.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

Temozolomide and irinotecan for relapsed glioma: Charing Cross Hospital experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12504-12504
Author(s):  
A. G. Young ◽  
P. J. Mulholland ◽  
A. D. Waldman ◽  
F. Roncaroli ◽  
K. S. O’Neill ◽  
...  
Keyword(s):  
Treatment Options ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Second Line Therapy ◽  
Durable Response ◽  
Free Survival ◽  
Line Therapy ◽  
Version 2.0 ◽  
Third Line ◽  
Dose Reductions

12504 Background: Patients (pts) with relapsed glioma have poor prognosis with few treatment options. Methods: Retrospective analysis was made of toxicity and outcome in pts with relapsed glioma treated between 2001–06 with temozolomide (TMZ, 75mg/m2/day, D1–21) & irinotecan (IRINO, 125mg/m2, D1, 8, 15), q35. Toxicity was graded using NCI-CTC version 2.0. Progression free survival (PFS) was calculated from start of TMZ/IRINO to relapse. Results: 24 pts (M:F, 15:9) were treated, comprising glioblastoma multiforme (GBM) (n=11); anaplastic astrocytoma (AA) (n=7); astrocytoma (n=4); oligoastrocytoma (n=2). Primary treatment following biopsy (n=12) or debulking surgery (n=12) was radiotherapy (RT) alone (n=12) or in combination with TMZ (n=12) (Stupp et al, 2005). At relapse, 10/24 pts received TMZ/IRINO as second-line therapy following TMZ+RT. 12/24 pts received third-line TMZ/IRINO, after TMZ alone (n=9), or TMZ/procarbazine (PCB) (n=2) or IRINO alone (n=1). 2/24 pts received fourth-line TMZ/IRINO, after TMZ then IRINO (n=1) & after TMZ/PCB then IRINO (n=1). 19/21 pts took enzyme-inducing antiepileptic drugs (EIAED). EIAEDs can potentially reduce IRINO exposure. 218 chemotherapy cycles (median, 5; range 1–42+) were given. Grade (G) 3 or 4 hematological toxicities were leucopenia (G3, n=3, 1.4%), neutropenia (G3, n=3, 1.4%; G4, n=1, 0.5%), lymphopenia (G3, n=64, 29%). 5 pts (20.8%) had cotrimoxazole prophylaxis; 1 pt developed PCP on it. 1 pt developed G3 urogenital sepsis. There were no other G3 or G4 toxicities. 13 cycles were delayed due to G2 infection (5.9%). 3 pts had dose reductions.1 pt died from AML; in retrospect symptoms appear to pre-date treatment start. Overall median PFS was 6 months (mo) (range 1.5–39.75+ mo). Overall 2 yr PFS was 28% (95%CI: 10–47%). Median PFS was: GBM 2.5mo (range 1.5–27.25+ mo); AA 11.5 mo (range 2–33.5+ mo). Median 2yr PFS was: GBM 27% (95%CI: 1–53%); AA 14% (95%CI: 0–40%) Conclusions: TMZ/IRINO is well tolerated in heavily pre- treated pts & warrants further evaluation. Long PFS was seen in pts with relapsed GBM & AA. Importantly, re-challenge including TMZ can induce durable response. [Table: see text]

Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1088-1088 ◽  
Author(s):  
Sylvia Adams ◽  
Sherene Loi ◽  
Deborah Toppmeyer ◽  
David W. Cescon ◽  
Michele De Laurentiis ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Imaging ◽  
Treatment Options ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
New Treatment ◽  
Combined Positive Score ◽  
Ecog Ps

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.

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