Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

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Optimal Treatment Order of Lenalidomide and Hypomethylating Agents for Lower-Risk Myelodysplastic Syndromes: A Report on Behalf of the MDS Clinical Research Consortium

Blood ◽

10.1182/blood.v128.22.4322.4322 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4322-4322 ◽

Cited By ~ 2

Author(s):

Rami S. Komrokji ◽

Mikkael A. Sekeres ◽

John Barnard ◽

Najla Alali ◽

Amy E. DeZern ◽

...

Keyword(s):

Overall Survival ◽

Lower Risk ◽

Research Funding ◽

Second Line ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Baseline Characteristics ◽

Research Consortium ◽

Treatment Order

Abstract Introduction While lenalidomide (LEN) is the standard of care for treatment of red blood cell (RBC) transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS) with chromosome 5q deletion (del 5q), it is widely used off-label in the non-del5q setting. In the MDS-002 and MDS-005 studies, 26% of TD non-del5q LR-MDS patients became RBC transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment option for TD anemia in lower-risk non-del 5q MDS after hypomethylating agents (HMAs). Thatrecommendationhas led to wide use of HMAs as frontline therapy after erythroid stimulating agents (ESA) failure in LR-MDS. The response rate to LEN after HMA failure, however, is not known, as MDS-002 and MDS-005 excluded patients previously treated with HMAs. To assess the best order of LEN and HMA in optimizing response potential in lower-risk MDS, we examined response rates to each drug when treatment order (LEN followed by HMA or HMA followed by LEN) differed. Methods We identified patients with LR- MDS (International Prognostic Scoring System (IPSS) low or intermediate-1 (int-1) risk groups) within the MDS Clinical Research Consortium database who received both LEN and HMA as first or second line therapy after ESA failure or patients who had low chance of response to ESA. We excluded patients with isolated del5q or del q + one additional cytogenetic abnormality. The primary objective was to compare rates of erythroid hematological improvement (HI-E), defined using 2006 International Working Group criteria (IWG 2006), between patients who received LEN as first line therapy followed by HMA as second line (LEN 1st line group) versus those who received LEN as second line therapy after HMA (LEN 2nd line group). Results We identified 144 patients who received both HMA and LEN as first and second line therapies: 80 patients were in group 1 (LEN 1st line) and 64 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table 1. There were no statistically significant differences between the 2 groups. The rate of HI-E was 20% (16/80) for the LEN 1st line group compared to 11% (7/64) in the LEN 2nd line group. (p=.046). There were no differences in response rates to HMA between the two groups: In the LEN 1st line group, response to 2nd line HMA was 30% (24/78) compared to 39% (25/64) for those who received HMA as first line (p=.2). There was no difference in overall survival (OS) between the two groups, The median OS was 79 months (mo) the LEN 1st line group compared to 61 mo in Len 2nd line group (p= .4). The rate of AML transformation was 9% in Len 1st line group compared to 22% in Len 2nd line group rate (p=.03). There was no difference in AML free survival (78mo versus 61mo respectively, p=0.4). In multivariable analyses adjusting for age, sex, and IPSS-R order of treatment still did not impact overall survival. Conclusion LEN yields a higher rate of HI-E in LR- MDS when used as first line therapy, but responses to HMAs were similar when used before or after LEN. The rate of AML transformation was lower when LEN was used as first line. The order of treatment does not impact overall survival. Lenalidomide should be used prior to HMA if it is to be considered for treatment of anemia in non-del5q LR-MDS. Table 1 Baseline characteristics Table 1. Baseline characteristics Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy; Boehringer-Ingelheim: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy; Cellectis: Research Funding.

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Patterns Of Care, Survival, and Costs Of Second-Line Treatment In Medicare Beneficiaries With Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v122.21.2936.2936 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2936-2936

Author(s):

Mark Danese ◽

Robert Griffiths ◽

Michelle Gleeson ◽

Tapashi Dalvi ◽

Jingyi Li ◽

...

Keyword(s):

Overall Survival ◽

Research Funding ◽

Patterns Of Care ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Significant Factors

Abstract Background DLBCL is the most common subtype of non-Hodgkin's lymphoma. Approximately 50% of DLBCL patients are over age 65. Patterns of care and outcomes in older patients receiving second-line therapy for DLBCL have not been well-characterized. Objective We analyzed patterns of care, overall survival and costs of care in a cohort of older DLBCL patients receiving second-line therapy. Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified a cohort age ≥66 with DLBCL diagnosed between 2000 and 2007. Patients had to receive first-line therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen, with or without rituximab. Second-line treatment was defined as either (a) ≥1 new agents < 90 days after discontinuing all first-line agents (refractory disease), or (b) ≥1 agents (including first-line agents) ≥90 days after completion of first-line therapy (relapsed disease). Rituximab monotherapy was excluded (n=736). Patients were enrolled from 12 months prior to diagnosis and followed through 12/31/2009. Observation ended at death, change from coverage, or 12/31/2009. We reviewed the therapies of each patient and classified them into 1 of 3 groups: aggressive, conventional, or palliative. Direct costs to Medicare were calculated using paid amounts over the 24-month period after initiating second-line therapy, weighted to account for censoring, and inflated to 2009 US dollars. Results There were 5,716 first-line DLBCL patients of whom 632 (11%) received second-line therapy (206 refractory and 426 relapsed). The most common aggressive regimens were methotrexate (n=60), [carboplatin, cyclophosphamide and etoposide (n=54)] and [cisplatin, cytarabine, and etoposide (n=23)]. The most common conventional regimens were [cyclophosphamide, doxorubicin, and vincristine (n=74)], [cyclophosphamide and etoposide (n=31)]. The most common palliative regimens were etoposide (n=68), [cyclophosphamide and vincristine (n=56)], fludarabine (n=26), and gemcitabine (n=25). Median survival was 13.4 months. Overall, survival was not statistically significantly different among the different treatment approaches in multivariate-adjusted survival models. However, patient characteristics differed significantly between these treatment groups with patients receiving aggressive treatment being younger than in the palliative treatment group (>80 years: 9.1% vs 30.6%; p<0.0001). Similarly refractory patients were more frequent in the aggressive vs. conventional treatment group (53.4% vs. 11.3%; p<0.0001). Significant factors affecting survival included female gender (hazard ratio [HR] 0.65, 95% CI 0.53-0.80), absence of B symptoms at diagnosis (HR 0.69, 95% CI 0.53-0.89), and presence of anemia at diagnosis (HR 1.26, 95% CI 1.02-1.55. Multivariate adjusted, cumulative 24-month costs for the reference group for all model variables was $117,442 (95% CI $78,270 to $156,615). Significant factors that modified this cost were age 75-79 (relative to age 66-69; $-28,860), age ≥80 ($-42,262), extranodal involvement at diagnosis ($-15,421), and anemia at diagnosis ($+23,047). Conclusions Second-line therapy for refractory and relapsed DLBCL was associated with high mortality and costs in the Medicare population. While selection bias limits comparison of aggressive vs. conventional therapies, our findings suggest a substantial unmet need in the second-line setting. Disclosures: Danese: Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Griffiths:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Gleeson:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Dalvi:Medimmune: Employment, stock Other. Li:Medimmune: Employment, stock Other. Deeter:Medimmune: Consultancy, Employment, stock Other.

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Pulsed high-dose erlotinib with gemcitabine as second-line therapy for pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.421 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 421-421

Author(s):

Christopher Larson ◽

Tony R. Reid

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Dose Escalation ◽

High Dose ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Recommended Phase Ii Dose

421 Background: The options for treatment of pancreatic cancer follow progression on first line therapy are limited and associated with significant toxicity. Erlotinib has been approved for treatment of pancreatic cancer in first-line therapy. We conducted a phase I dose-escalation trial of erlotinib in combination with gemcitabine for patients that had failed first-line therapy. Erlotinib was administered by a novel pulse-dose schedule where the drug was given orally for 3 days every two weeks. Purpose: Assess the safety and determine a recommended phase II dose for pulsed high dose erlotinib in combination with gemcitabine for pancreatic cancer, and obtain preliminary data on activity. Methods: Patients with pancreatic cancer that progressed on or after first-line therapy were treated in a dose escalation study with erlotinib at 750 to 2,000 mg daily for three days every two weeks in combination with weekly gemcitabine at 1,000 mg/m2 for three weeks on and one week off. Results: No dose limiting toxicities were encountered and erlotinib-induced rash was mild and transient. Median overall survival was 6.7 months and 12-month overall survival was 27%. Progression free survival but not overall survival was longer in patients who did not previously receive gemcitabine. Rash was not associated with longer survival. Conclusions: The recommended phase II dose is erlotinib 2,000 mg daily for three consecutive days every two weeks in combination with gemcitabine. Tolerability was excellent, and outcomes were better than expected for second-line therapy in pancreatic cancer. Further studies are warranted, both as therapy after first-line and as first-line therapy for patients unable to tolerate more aggressive regimens. Clinical trial information: NCT02154737.

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Natural History of Skeletal Related Events in Patients with Multiple Myeloma Who Received First- and Second- Line Therapy with Novel Agents: Results from a Single Center Analysis in 620 Patients

Blood ◽

10.1182/blood-2019-123606 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4326-4326

Author(s):

Evangelos Terpos ◽

Nikolaos Kanellias ◽

Eftathios Kastritis ◽

Maria Gavriatopoulou ◽

Vassilis Koutoulidis ◽

...

Keyword(s):

Research Funding ◽

Novel Agents ◽

Long Bone ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Skeletal Related Events ◽

First Relapse

Introduction: Skeletal-related events (SREs) that include pathological fractures, spinal cord compression (SCC) and need for radiotherapy or surgery to the bone are frequent complications of multiple myeloma (MM). Although the incidence of SREs at diagnosis is well-documented, there is limited information for the natural history of SREs during treatment with novel agents. Thus, we evaluated the SRE rate in MM patients who received frontline and second line therapy with proteasome inhibitors (PIs) or immunomodulatory drug (IMiD)-based therapies and explored possible correlations with disease or genetic features and type of treatment. Methods: MM patients who received frontline therapy in our center (Department of Clinical Therapeutics, University of Athens, Greece), between 2007-2017, were included in this analysis. Patients had a whole-body skeletal survey using either conventional radiography (WBXR) or low-dose CT (WBLDCT) at diagnosis and then at the time of relapse or whenever clinically indicated. Magnetic Resonance Imaging (MRI) of the spine and pelvis at diagnosis was recorded when available. SNPs in genes that are involved in bone destruction in osteoporosis were also evaluated: LRP5 (rs4988321), GC vitamin D (rs4588), TNFRSF11A (rs3018362), DKK1 (rs1569198), RANKL (rs9594759), OPG (rs6469804) and ERS1 (rs1038304). Results: In total, 620 consecutive patients with symptomatic MM (316M/304F, median age: 65 years) were studied. The median follow-up was 54 months. At diagnosis, osteolytic disease was present in 408 (66%) patients. MRI was available in 390 patients: 149 (38%) patients had focal, 139 (36%) diffuse, 81 (21%) normal and 21 (5%) variegated pattern of marrow involvement. SREs were observed in 271 (44%) patients at diagnosis: 213 (34%) presented with pathological fractures (183 with vertebral fractures, 18 with rib fractures and 15 with long bone fractures; 32 patients had both vertebral and long bone or rib fractures), while 34 (5.5%) patients needed surgery to bone, 45 (7.2%) radiotherapy and 31 (5%) patients presented with SCC. The incidence of SREs was higher in patients with osteolytic lesions (76.4% vs. 12.4%, p<0.0001) or abnormal MRI pattern (49% vs. 11.3%, p<0.0001) at diagnosis. No correlation was found between the presence of SREs at diagnosis and a specific SNP of those studied. Frontline therapy with IMiD-based regimens was given in 38% of patients; 27% patients received bortezomib-based regimens and 28% both IMiD and bortezomib-based therapies (VTD or VRD); 7% received only conventional chemo. Bisphosphonates (BPs) were given to 465 patients (75%) at diagnosis; the vast majority (91%) received zoledronic acid. The remaining 155 patients did not receive upfront BPs, mainly due to renal insufficiency. During first line treatment, 39 (6.3%) patients developed a SRE: 25/341 (7.3%) on bortezomib- (including combos with an IMiD) and 14/235 (6%) on IMiD-based regimens. At the time of first relapse, 4.5% of patients presented with new fractures and 12% required local radiotherapy to bone (SRE rate: 16.5%). The rate of SREs at first progression was much higher in patients who did not receive upfront BPs (92.3% vs. 7.7%). There was no difference in the incidence of SREs at first relapse between patients who received PI- vs. non-PI-based regimens as first line therapy (54.2% vs. 45.8%, p=0.544). During second line therapy, 12.2% of patients developed a SRE, with no difference regarding the second line therapy (PI- or IMiD-based regimens). In total, 126 (20.3%) patients developed at least one SRE, during the course of the first and second line of therapy; this was more common in those who presented with an SRE at diagnosis (33% vs 12%; p<0.03). Conclusions: Our data, which constitutes one of the few systematic reports on the incidence and characteristics of SREs in the era of novel agents, indicate that SREs remain a significant complication in MM. Despite high response rates after first line therapy and the broad use of BPs, more than 20% of patients develop a new SRE during the first and second line treatment or at the time of first relapse. Importantly, patients who do not receive BPs due to renal impairment develop very frequently SREs, suggesting an unmet need in this setting. More effective frontline therapies or more potent bone-targeted agents (denosumab or anti-sclerostin drugs) may manage to further reduce the SREs rate in MM patients, especially in those who cannot receive BPs. Disclosures Terpos: Celgene: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria. Kastritis:Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Gavriatopoulou:Amgen: Honoraria; Takeda: Honoraria, Other: Travel expenses; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Dimopoulos:Sanofi Oncology: Research Funding.

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Outcome of Risk Adapted Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia in Children: Results From a Single Institution

Blood ◽

10.1182/blood.v118.21.4237.4237 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4237-4237

Author(s):

Asim F Belgaumi ◽

Asem Bukhari ◽

Mohammed Al-Mahr ◽

Amal Al-Seraihy ◽

Hazem Mahmoud ◽

...

Keyword(s):

Overall Survival ◽

Induction Therapy ◽

Late Relapse ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Hematopoietic Stem ◽

First Line Therapy ◽

Line Therapy ◽

Significant Difference

Abstract Abstract 4237 Although the outcome of first line therapy for childhood ALL has improved significantly, the results of second line therapy remains suboptimal. The most important predictive factors identified for second line therapy are timing and site of relapse; early relapse and bone marrow (BM) involvement invoking poorer outcomes. At our institution we have utilized a risk stratified therapeutic strategy for relapsed/refractory ALL which includes these factors. Re-induction for patients with first remission (CR1) duration of <18 months or those with remission failure was with high dose cytarabine (HDAraC) containing regimens, most often with idarubicin (Ida). For patients with CR1 >18 months, we utilized a standard 4-drug (prednisone, vincristine, daunomycin, asparaginase [PVDA]) induction regimen. Patients who relapsed in the BM while on chemotherapy or within 1 year of being off therapy were eligible for hematopoietic stem cell transplantation (SCT) after achieving CR, as were patients with isolated extra-medullary relapse with CR1 <18 months. Patients with late relapse were treated with post consolidation maintenance chemotherapy alone. Data collected prospectively in our database were reviewed. ALL patients who relapsed after receiving first line therapy at our institution and those who were referred to us at first relapse were included in this analysis. Only overall survival (OS) is presented as all patients who failed to achieve a CR or relapsed after achieving CR eventually died regardless of further therapeutic interventions. Fifty-nine patients with ALL failed their first line therapy between January 1, 2005 and May 31, 2011. There were four induction failures and 55 relapses. These 59 patients included 39 males; 53 of the patients had B-cell ALL and 6 had T-cell ALL. The age at original diagnosis ranged from 0.55 to 13.8 years (mean 6; median 4.8; SEM 0.50) whereas the age at first failure ranged from 0.68 to 16.4 years (mean 8.0; median 7.8; SEM 0.50). 36/55 (65.5%) relapses occurred on first line chemotherapy, 17 (30.9%) after completion of therapy and 2 (3.6%) following SCT. For the relapsed patients, the duration of CR1 ranged from 0.09 to 9 years (mean 2.0; median 1.7; SEM 0.22); 24 (44.4%) patients relapsed less than 18 months from CR1. 36 (61%) patients had isolated BM relapse, 13 (22.1%) had isolated extra-medullary (7 CNS; 6 testicular) and the remaining 10 had BM with other sites. Twenty four patients (40.7%) were re-induced with HDAraC/Ida (HIda), 28 (47.5%) with PVDA, 4 (6.8%) Fludarabine/AraC (FA) and 3 did not receive any second line therapy. For those who were treated 37 (62.7%) achieved a CR; 13 of the 19 patients who did not achieve CR with second-line therapy received third-line induction therapy (9 FA; 1 HIda; 1 VM26/AraC; 1 PVDA; 1 VP/CTX) and 7 (53.8%) achieved CR. The overall survival for all 59 patients at 2 years is 45.3%; for those who achieved CR the overall survival at 2 years is 64.7%. When we compared those patients who had CR1 durations >18 months with those who were induction failures or had CR1 duration <18 months, we found no significant difference in CR2 induction rates (76.7% v. 80%; p=1.0), nor in OS (56.9% v. 34.5% at 2 years; p=0.14). CR induction rates did not change when we further categorized CR1 duration into 18 months, 18–36 months and >36 months (80% v. 72.2% v. 80%; p=0.74). However, the OS was significantly higher for the >36 month group (83.3%; p=0.023) when compared to the other 2 groups (38.7% and 38.4%, respectively). In patients with <36 months of CR1, HSCT resulted in a significantly improved OS as compared to chemotherapy alone (51.4% v. 30.9 at 2 years; p=0.05). For those patients who achieved a CR2 there was no difference in the OS between those who underwent HSCT v. those who continued on chemotherapy (68% v. 58.5% at 2 years; p=0.33). Patients who achieved a CR after 2nd line therapy fared much better than those who achieved a CR after 3rd line therapy (25/36 [69.4%] alive v. 2/7 [28.6%] alive; OS at 2 years 68.3% v. 29.2%; p=0.06). In conclusion, we believe that this risk stratified approach to the treatment of relapsed/refractory ALL in children is effective. While the majority of the patients can be re-induced into remission, maintenance of the remission is dependent on the duration of CR1; patients with late relapse do as well as treatment naïve patients. Increased intensity induction therapy for early relapses and SCT for patients with <36 months of CR1 may be beneficial. Disclosures: No relevant conflicts of interest to declare.

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Impact of Therapy Choice on Fatigue in Adults with Immune Thrombocytopenia

Blood ◽

10.1182/blood-2020-139746 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 19-20

Author(s):

Jennifer Diraimo ◽

Caroline Kruse ◽

Michele P. Lambert ◽

Alexandra Kruse

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Treatment History ◽

First Line Therapy ◽

Line Therapy

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Both disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with this rare condition. Here, we compare self-reported fatigue and its impact among adult ITP patients and determine whether these fatigue levels differ depending on treatment status. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) reported they have never received treatment for their ITP, while 46% (n=166) have in the past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 47 (26%) use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 78 (43%) are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%), other second-line treatments (such as MMF, dapsone etc.), and "other" therapies including complementary treatments (14%). Overall, 93 (23%) reported having had a splenectomy at some point to manage their active ITP. When asked to reflect on general tiredness, 98% of patients (n=310) reported being tired overall, with 55% reporting feeling tired 'almost always/often' regardless of treatment group or type. Those who have never been treated reported they felt tired 94% of the time, and 55% reported feeling tired 'almost always/often'. Among those who are not currently on treatment (but have received therapy in past), 99% reported feeling tired overall, and 50% reported feeling tired 'almost always/often'. Respondents using a first line therapy reported feeling tired overall 100% of the time, and reported feeling tired 53% 'almost always/often'. Respondents using a second line therapy reported feeling tired 99% of the time, and indicated they were tired 59% 'almost always/often'. There were no significant differences between these treatment types and groups identified. When asked to reflect on fatigue levels over the last seven days, collectively, 86% reported fatigue, and 30% reported experiencing it 'very much/quite a bit'. Among those who had never been treated, 85% reported fatigue, and indicated they felt fatigue 27% of the time 'very much/quite a bit'. Respondents who were not receiving treatment reported feeling fatigue 84% of the time, of which 26% was experienced 'very much/quite a bit'. Among those receiving a first line therapy, 90% reported fatigue in the last seven days, and 34% reported they experienced this 'very much/quite a bit'. Those using a second line therapy reported feeling fatigue 91% of the time, and 29% reported this was 'very much/quite a bit'. There were no significant difference among these treatment types and groups. Conclusion: Reported fatigue and overall tiredness are high among those currently on treatment, not on treatment, and those who have never been treated for their ITP. We did not find that fatigue levels were related to treatment type or group, indicating that the underlying causes may not be platelet count, or disease severity, but rather a combination of factors associated with having an unpredictable chronic disease. The multi-faceted effects of ITP often take a significant toll on patients' quality of life. The registry continues to collect data with the intent of understanding the longitudinal impact of ITP and in future with more of a sample size we can learn if these trends continue. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Octapharma: Consultancy, Research Funding; Bayer: Consultancy; Argenix: Consultancy; ClinGen: Honoraria; Platelet Disorder Support Association (PDSA): Consultancy; 22qSociety: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; RDMD ITP study: Consultancy; Sysmex: Research Funding; AstraZeneca: Research Funding.

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Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma

Modern Oncology ◽

10.26442/18151434.2020.3.200353 ◽

2020 ◽

Vol 22 (3) ◽

pp. 142-148

Author(s):

L. V. Bolotina

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Unresectable Hepatocellular Carcinoma ◽

First Line Treatment

Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late disease intelligence does not frequently allow radical treatment, palliative methods remain the only option of survivability enhancement and improving the patients quality of life. Lenvatinib was approved as the first-line drug in the treatment of unresectable hepatocellular carcinoma based on the data of the REFLECT trial, in which the drug demonstrated achieving the patients overall survival (OS) comparable to the activity of sorafenib (13.6 months for lenvatinib vs 12.3 months for sorafenib; hazard ratio HR 0.92; 95% confidence interval CI 0.791.06). At the same time, significant inferiority of lenvatinib was observed for secondary endpoints: progression-free survival PFS (7.4 months for lenvatinib vs 3.7 months for sorafenib; HR 0.66; 95% CI 0.570.77;р0.0001), time to progression (8.9 months for lenvatinib vs 3.7 months for sorafenib; HR 0.63; 95% CI 0.530.73;р0.0001) and objective response rate ORR (24.1% for lenvatinib vs 9.2% for sorafenib). The further analysis of the results of the REFLECT study revealed the additional factors impacting patients survival, such as the level of a-fetoprotein (AFP) before treatment, treatment ORR, performance of subsequent antitumor therapy and procedures after completion of the target first-line therapy. In patients responding to lenvatinib in the first line and further receiving any second-line therapy, the mOS was 25.7 months as compared with the median overall survival (mOS) of 22.3 months in patients responding to sorafenib and receiving further second-line therapy. Additionally, in responders switching from lenvatinib to sorafenib, the mOS was 26.2 months. In the recently published comparative study of lenvatinib and transarterial chemoembolization on the BCLC B stage, inferiority of lenvatinib was demonstrated in terms of OS, PFS and ORR in certain patient categories. Considering the data obtained in the REFLECT population, where in patients achieving the RR to the first-line treatment with lenvatinib and further receiving the local antitumor procedures the mOS increased to 27.2 months (95% CI 20.729.8), prescribing target and locoregional therapy in certain cases in this very sequence is possible. The recently published data about administration of lenvatinib outside of the inclusion criteria for the REFLECT trial, have proved the efficacy and safety of this drug administration in real clinical practice, thus significantly expanding our understanding of the key role of lenvatinib in the first-line treatment of unresectable hepatocellular carcinoma.

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Outcomes after first-line therapy for immune/immune or immune/VEGF combinations.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.706 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 706-706

Author(s):

Francesca Jackson-Spence ◽

Agne Jovaisaite ◽

Michael Grant ◽

Wing-Kin Liu ◽

Thomas Butters ◽

...

Keyword(s):

Combination Therapy ◽

Immune Therapy ◽

Response Rates ◽

Second Line ◽

Front Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Group I

706 Background: The introduction of first line immune combination or immune/VEGF therapy in metastatic renal cancer has changed treatment landscape. Here we compare outcomes of these combinations with patients treated with first line sunitinib. The focus is on the impact of subsequent treatments. Methods: This retrospective analysis was performed at Barts Cancer Institute for consecutive patients from April 2015 when front line immune therapy was first used at our institution. Only patients enrolled on reported prospective trials were included to avoid selection bias. Patients were treated with VEGF targeted therapy (n=35) (group V), PD-1 + CTLA4 (n=15) (group I/I) or a combination of PD-L1 + VEGF TKI inhibitor (n=29) (group I/V). The primary analysis focused on the proportion of patients who received second line therapy and their outcome. Results: 79 patients received first line therapy for clear cell RCC. IMDC good, intermediate and poor risk occurred in 27.8%, 60.8% and 11.4% respectively. Front line response rates for V, I/I and I/V groups were 34.3%, 46.7% and 65.5% and PFS in V, I/I and I/V groups were 11mo (95%CI 6-16), 18mo (95% CI 0-41) and 36mo (95% CI 13-59), respectively (P= 0.016). OS in the 3 groups were immature but not significantly different. Second line therapy occurred in 87.5%, 92.9% and 81.8% in the V, I/I and I/V groups respectively (in those who progressed after initial therapy). Second line response rate post first line V, I/I and I/V were 11%, 0% and 0% respectively as per RECIST 1.1. 63% of patients receiving VEGF front line therapy subsequently received immune therapy. 95% of patients receiving first line immune/immune or immune/VEGF combination therapy received VEGF therapy in the second line. Only 70% of patients who progressed on second line therapy got 3rd line therapy across all arms. Conclusions: Response rates after front line immune combination therapy are modest. The sequencing of PD-1 therapy after VEGF monotherapy appears particularly relevant in outcomes. A high proportion of patients are sequencing therapy and reaching third line which may help improve outcomes.

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1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1520 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S680-S681

Author(s):

Carly Heck ◽

Judith Martin ◽

Marcia Kurs-Lasky

Keyword(s):

Drug Allergy ◽

Health Concern ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Comparison Results ◽

Significant Difference ◽

Recommended Therapy

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures

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Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

Journal of Clinical Oncology ◽

10.1200/jco.2004.11.037 ◽

2004 ◽

Vol 22 (7) ◽

pp. 1209-1214 ◽

Cited By ~ 761

Author(s):

Axel Grothey ◽

Daniel Sargent ◽

Richard M. Goldberg ◽

Hans-Joachim Schmoll

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Cytotoxic Agents ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

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