Outcomes in Patients with Chronic Myeloid Leukemia (CML) Who Are Treated with Imatinib As Front Line Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3740-3740
Author(s):  
Kendra L. Sweet ◽  
Najla H Al Ali ◽  
Jeffrey E Lancet ◽  
Ben Creelan ◽  
Sara Tinsley ◽  
...  
Keyword(s):  
Second Generation ◽  
Cytogenetic Response ◽  
Refractory Disease ◽  
Second Line ◽  
First Line ◽  
Loss Of Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response

Abstract Abstract 3740 Background: Based upon dramatic improvement in major and complete cytogenetic response with imatinib (STI571) in the phase III International Randomized Study of Interferon Versus STI571 (IRIS) trial, imatinib was approved for first-line treatment in CML. Despite this success, five-year follow up of this trial showed only 69% of patients remained on imatinib. Other long-term studies suggest that up to 50% of patients may require interruption or discontinuation of imatinib due to primary or secondary resistance, drug intolerance, or progression to accelerated phase (AP) or blast crisis (BC). Methods: The Total Cancer Care (TCC) database was used to identify all patients with CML treated with imatinib as first-line therapy between 1992 and 2010 at Moffitt Cancer Center (MCC). “Imatinib-refractory” was defined as absence of complete hematologic response by 3 months, or cytogenetic response by 6 months. “Loss of response” was defined as loss of best response while remaining on the dose of imatinib that was previously therapeutic. Progression-free survival (PFS) was defined as time from treatment to loss of best response, or progression to AP or BC. Descriptive data were reported, chi square test was used for categorical variables, and Kaplan Meier method was used for OS and PFS. Log rank test was used to compare survival times between groups. Statistical analysis was done using SPSS statistical software, version 19. Results: Of a total of 540 CML patients evaluated, 304 (56%) received imatinib as first-line therapy, with 51% being male and 49% female. Five patients were diagnosed before 2001 and median age was 49.5 years. Median time on imatinib was 23 months. With a median follow up of 72 months (95% CI 67–76), the 5-year OS was 78% and median OS was not reached. Of 304 patients, 139 (46%) required a change to second generation TKI's. Causes for imatinib discontinuation included: intolerance in 48 (35%) patients, refractory disease in 34 (24%) patients, loss of response in 26 (19%) patients, and progression to AP or BC in 31 (22%) patients. In patients switched due to intolerance, refractory disease or loss of response median PFS and OS were not reached. Median OS was 53 months (95% CI 5.4–101.3) in patients whose therapy was changed due to progression to AP or BC (P=0.000) (Figure 1). Overall, 82 (27%) patients progressed to AP or BC either on first or second line therapy, and 25 (8%) developed kinase domain mutations (KDM). Of the 25 patients with KDM, 13 (52%) developed T315I mutations. Conclusion: Despite the success of imatinib in improving outcomes in CML, nearly half of all patients will require discontinuation of the drug with a change to second line TKI's. This change does not appear to negatively impact OS, with the exception of therapy changes due to overt progression into AP or BC. Our results suggest that most imatinib failures may be salvaged with second generation TKI's without significant impact upon overall survival. Disclosures: No relevant conflicts of interest to declare.

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.

Desmoid tumor (DT) management in dedicated sarcoma medical oncology clinic in a developing country: Lessons learnt.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22541-e22541
Author(s):  
Sameer Rastogi ◽  
Aditi Aggarwal ◽  
Ekta Dhamija ◽  
Adarsh Barwad ◽  
Rambha Panday ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Medical Oncology ◽  
Case Reports ◽  
Tertiary Care ◽  
Second Line ◽  
First Line ◽  
Female Ratio ◽  
First Line Therapy ◽  
Line Therapy

e22541 Background: There is lack of data about desmoid tumors from India except case reports. It is not known how these patients are dealt with outside tertiary care centres who lack expertise. Methods: We retrospectively analysed all patients of DT from a prospectively maintained database who were referred to AIIMS Sarcoma Medical Oncology Clinic from January 2016 till 2019. Results: There were total of 56 patients with male: female ratio of 3:4. Median age was 26 (3-57) years. Extremity was most common site (57%) and median tumour size was 12 (range 3-20) cm. One patient (1.8%) had FAP and 1 (1.8%) had multifocal disease. A total of 27 patients received first treatment outside our institute and was primary surgery in all (100%). However, of the remaining 29 patients who primarily presented to us, surgery was done only in 3 (10%) because of patients choice and pelvic location. Five patients were kept under observation and all are doing well. Tamoxifen with celecoxib was most common first line therapy in 80% (40/50) with other options being sorafenib (6/50) and chemotherapy (4/50). Chemotherapy was used in abdomen (3/4) and head neck (1/4) primary patients. Menstrual irregularities including amenorrhoea was most common toxicity in 33% (13/40) with tamoxifen combination and a cause of concern in this cohort of young females leading to discontinuation of therapy inspite of SD in 54% (7/13) patients. Second line therapy was started in 20 patients with sorafenib being most common (13/20), others being chemotherapy (4/20), tamoxifen combination (2/20) and imatinib (1/20). Of all 19 patients on sorafenib, 10 (53%) experienced Hand Foot Syndrome. None discontinued sorafenib due to HFS. After median follow up of 15 months, median progression free survival (PFS) with first line was 29 months (11-46) and with second line it was not reached. There have been three deaths till date (5.3%), all were non-extremity primaries. Conclusions: In Indian setup, majority of patients presenting outside tertiary care centre undergo surgery as the first line therapy without any inclusion of medical therapy. This might be attributed to lack of awareness about medical therapy and natural trajectory of disease. Tamoxifen though was a commonly used option, led to toxicity which is of concern in young Indian patients leading to discontinuation. Sorafenib is well tolerable except HFS but longer follow up is needed for efficacy analysis.

Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1790-1790
Author(s):  
Petra Obrtlikova ◽  
Anna Jonasova ◽  
Magda Siskova ◽  
Eduard Cmunt ◽  
Adela Berkova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

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

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

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

scholarly journals Experience of Generic Imatinib As a First Line Therapy for Patients with Chronic Myeloid Leukemia in a Single Reference Institution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5916-5916
Author(s):  
Gabriel Carvalho Pereira ◽  
Fernanda B da Silva ◽  
Luisa Espirito Santo Oliveira ◽  
Pedro Marques Garibaldi ◽  
Lorena Lobo Figueiredo-Pontes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Rate Of Response

Background: The treatment of chronic myeloid leukemia (CML) was revolutionized by the approval of Gleevec (imatinib mesylate) by the FDA in 2001. In low-middle-income countries, due to economic issues related to the high cost of this treatment, scientific governmental entities started to produce and release a generic imatinib in 2013. High quality data about the security profile and efficacy of generic imatinib treatment are still needed. Aims: We herein aimed to evaluate the 6 years follow up of CML patients treated with generic imatinib as first line therapy. Patients and Methods: We evaluated a retrospective cohort of 39 patients diagnosed with CML at a single institution, during the period between December 2001 and July 2019, that had used only generic formulation of imatinib since diagnosis; and analyzed their rate of response to treatment as a primary goal and adverse events and survival outcomes as secondary goals. Responses were evaluated according to ELN 2013. Event-free survival and overall survival were measured from starting date of treatment until: loss of molecular response or death from any cause, and until death from any cause or last seen, respectively. Results: The cohort of 39 patients treated with generic imatinib as first line therapy was composed of 23 men (59%) and 16 women (41%), with median age at diagnosis of 52 years (16-74). The median follow up time was 24 months (8-68), and the median duration of generic imatinib therapy was 19 months (5 - 68). Most of the patients were diagnosed at chronic phase (92%), with only 2 accelerated phase and 1 myeloid blast crisis. Risk stratification according to Eutos, Sokal and Hasford score was low in 92%, 67% and 80%; intermediate in 0%, 30% and 6% and high in 8%, 3% and 14%, respectively. Six different brands of generic imatinib were used (Cristalia, Instituto Vital Brasil, FURP, EMS, Fiocruz and Eurofarma); the most frequently used were Cristalia and Instituto Vital Brasil. The median number of brands used per patient was 2 (1-5). Patients received 400 mg of generic imatinib daily; the dose was increased to 600 mg in 4 patients due to sub-optimal response during follow up. The rate of hematologic response with treatment was 97% and median time to reach it was 1 month (1-7). The rate of response at 3, 6 and 12 months was 74%, 60%, and 92% for optimal cytogenetic response, and 69%, 61%, and 26% for optimal molecular response. The probability to reach deep molecular response at each year of follow up was 41% at 1st year, 52% at 2nd year, 46% at 3rd year, 50% at 4th year, 50% at 5th year, and 50% at 6th year. The probability to reach a molecular response 4.5 at each year of follow up was 10% at 1st year, 23% at 2nd year, 30% at 3rd year, 50% at 4th year, 50% at 5th year, and 50% at 6th year. Hematologic toxicities were frequent during the first three months of therapy. Reported non-hematologic adverse events were hypophosphatemia (62%), diarrhea (30%), cramps (30%), liver toxicity (28%), nausea (18%), bone pain (18%), edema (15%), rash (8%), and hypomagnesaemia (2.5%). Eight percent of patients evolved with deterioration of renal function during the treatment period, but its relationship with generic imatinib was not well established. Two patients (5%) needed a dose reduction because of adverse events. Eight (20.5%) patients switched to second line tyrosine-kinase inhibitors, five (13%) due to resistance and three (8%) due to side effects (severe hepatotoxicity, diarrhea, and rash). Three patients progressed after switching to another tyrosine kinase inhibitor. After a median follow up of 24 months, the event free survival rate was 80% and the overall survival rate was 100%. Conclusion: The rate of complete cytogenetic response, resistance, and intolerance after use of generic imatinib was not worse than the rates described in the long-term follow up of the IRIS trial (N Engl J Med 2017; 376:917-927). Deep molecular response rates seen in the cohort of patients on generic imatinib were inferior to the ones in the IRIS trial, but overall survival was not impacted. Hypophosphatemia was observed in a high percentage of patients, although it has not been reported in other cohorts on generic imatinib. Prospective randomized studies are needed to allow better conclusions regarding the comparative efficacy and safety of generic imatinib. Disclosures Figueiredo-Pontes: Novartis: Honoraria.

scholarly journals A Multicenter, Prospective Study for Pediatric Chronic Myeloid Leukemia in Chronic Phase: The JPLSG CML-08 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3605-3605
Author(s):  
Hiroyuki Shimada ◽  
Akihiro Watanabe ◽  
Masaki Ito ◽  
Chikako Tono ◽  
Haruko Shima ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Chronic Phase ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Tyrosine kinase inhibitor (TKI) has been used in pediatric chronic myeloid leukemia (CML) for more than 10 years, but only a few prospective clinical studies have been conducted in pediatric patients with CML due to their rarity. We conducted the JPLSG CML-08 study to determine the efficacy and tolerability of TKIs in children and adolescents with newly diagnosed CML in chronic phase (CML-CP). Methods: The JPLSG CML-08 study was a prospective multicenter observational study (UMIN000002581). Patients under 18 years of age with untreated BCR-ABL1-positive CML-CP were eligible and treated according to the modified ELN-2009 recommendation, and the efficacy and safety of TKIs were evaluated. Results: From October 2009 until September 2014, 79 patients were enrolled in 46 hospitals in Japan. A total of 78 patients (49 males and 29 females) were eligible for inclusion. Median age at diagnosis was 11 years (range, 1-17). Median observational period for survivors was 82 months (range, 48-118). Median WBC, Hb and platelet counts were 275x10 9/L (range, 8-765), 9.6g/dL (range, 5.8-14.6) and 560x10 9/L (range, 110-2875), respectively. Splenomegaly was found in 76%. High risk of Sokal, Hasford, EUTOS, and ELTS scores were observed in 21, 13, 27, and 9%, respectively. Clonal chromosome abnormalities in Ph-positive cells occurred in 1 patient at diagnosis. Imatinib, dasatinib, and, nilotinib were used as a first-line treatment in 69 (88%), 7 (9%), and 2 (3%) patients, respectively. The median initial dose of imatinib, dasatinib, and nilotinib was 276, 63, and 262mg/m2, respectively. 5y-PFS and OS was 96.2% (95%CI, 88.6 to 98.7%) and 97.4% (95%CI, 90.1 to 99.4%), respectively. Deaths were observed in 2 patients due to transplant complications. Hematopoietic cell transplantation was conducted in 14 patients (18%). Nine patients (12%) discontinued TKI with the aim of treatment-free remission (TFR), and five of them achieved TFR. In 69 patients with first-line imatinib, complete hematologic response was achieved in 95.7% at 3 months, complete cytogenetic response in 75.4% at 12 months, major molecular response (MMR) in 40.1% at 18 months, and MR4.0 in 52.8% at 60 months; If a transplant was performed, the follow-up period was censored at the date of transplant. Of the 69 patients, 52% changed treatment from imatinib to another TKI or transplant due to poor response, and 20% did due to intolerance. The most common cause of intolerance to imatinib was musculoskeletal events. BCR-ABL1 (IS) &lt;10% at 3 months strongly correlated with higher achievement of MMR, MR4.0, and MR4.5. The EUTOS score was significantly associated with achievement of IS &lt;10% at 3 months. Patients with a first-line second-generation TKI had a higher cumulative incidence of MR4.5 (P = 0.0191) than patients with a first-line imatinib. Second-generation TKI was used as first-line therapy only in patients older than 9 years, but other clinical characteristics, including risk scores, did not differ significantly between the two groups. The incidence of grade 3/4 adverse events (≥ 10%) included neutropenia (47%), anemia (39%), leukopenia (13%), arthralgia (13%), and myalgia (11%) for imatinib, neutropenia (21%), anemia (13%), and thrombocytopenia (11%) for dasatinib, and neutropenia (14%), elevated ALT (14%), hyperbilirubinemia (14%), skin rash (14%), and high CPK (14%) for nilotinib. Gastrointestinal bleeding was an adverse event specific to dasatinib (11% in all grades). Conclusion: This clinical study extends and confirms previous data showing that first-line treatment with imatinib is effective in children and adolescents, with response rates similar to those seen in adults. Although longer follow-up is needed to fully assess the long-term toxic effects, adverse events with imatinib, dasatinib, and nilotinib have been acceptable. As reported in adults, there was an advantage in selecting second-generation TKI over imatinib as first-line therapy to achieve deep molecular remission (DMR). Since discontinuation of TKI after achieving DMR is the preferred strategy, second-generation TKI is expected to become the standard therapy for children and adolescents. Disclosures No relevant conflicts of interest to declare.

Prescribing preferences (PPrefs) of U.S.-based medical oncologists (MOs) for choice of therapy after failure of first-line FOLFOX plus bevacizumab (FFB) in patients with metastatic colorectal cancer (MCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 533-533
Author(s):  
Johanna C. Bendell ◽  
Susan L. Britton ◽  
Maria Lankford ◽  
Arden Buettner ◽  
Mark R. Green ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Real Life ◽  
Phase Iii ◽  
Audience Response ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Phase Iii Trials

533 Background: Phase III trials have tested biologic (bio) agents (bevacizumab [bev], anti-EGFR antibodies, ziv aflibercept [ziv]) plus chemotherapy (CT) vs. CT alone after failure of first-line therapy in patients given CT + bev first line. Several have shown improvements in progression-free and overall survival (OS) with the CT + bio approach, but it is not clear how these therapies are being used in the “real life” setting. Methods: Since 3/2013 PPrefs for this setting among 276 MOs were studied using a validated, proprietary, live, case-based market research tool. A core scenario and variations based on KRAS status and first-line therapy outcome were tested (S1, S2, S3, S4). PPref data acquired using blinded audience response technology. All sources of research support were blinded. Core scenario: 49 yr old female with cecal mass, liver/lung metastases, confirmed wt KRAS for S1-3, given FFB first line. S1: FFB x 16 wks → excellent PR → 5FU bev X 16 wks → progressive disease [PD]; S2: FFB x 16 wks → excellent PR → bev alone x 16 wks → PD; S3: FFB → stable disease [SD] x 5 months as best response [BR] → PD; 4) Here changed to mutKRAS; FFB x 8 wks → PD as BR. Results: Findings shown below (Table). Conclusions: In scenarios with wt KRAS, first-line response to FFB, a majority plan bev again second line. If BR to FFB is SD in WT KRAS, anti-EGFR antibody-based therapy is used more often. In S 1-3, ziv is the PPref of 7 - 14% of MOs studied. With mutKRAS and PD as BR to FFB, use of an antiangiogenic + second-line CT is preferred by > 80%, nearly equally split between bev and ziv. Recent phase III trial data showing OS benefits are reflected in current MOs first failure PPrefs. [Table: see text]

Treatment Patterns and Outcomes Following Initial Relapse in Patients with Relapsed Systemic Immunoglobulin Light Chain Amyloidosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3338-3338
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction Immunoglobulin light chain amyloidosis (AL Amyloidosis) is a plasma cell disorder characterized by deposition of misfolded insoluble protein fibrils (composed of monoclonal κ or λ light chains) in tissues causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT), when eligible, are standard treatment options but relapses remain inevitable for most patients. However, there is a paucity of literature describing relapsed or refractory patients. We performed a retrospective study to analyze the outcomes upon relapse and the impact of type of therapy and retreatment with the same therapy at relapse. Methods Clinical and laboratory data of 1327 consecutive patients with systemic AL amyloidosis seen at Mayo Clinic within 90 days of their diagnosis, between 2006 and 2015, was collected by chart review and analyzed retrospectively. Of these patients, 219 (16.5%) were lost to follow-up. Among the remaining 1108 patients, 366 patients experienced a documented hematological or organ relapse or progression requiring change of first line or start of second line therapy and form the current study population. Overall survival (OS) was calculated from start of second line treatment or progression mandating therapy until death from any cause or the date of last follow up. The OS was estimated using the Kaplan-Meier method and log rank test was used to estimate the difference in survival curves. Results The median age was 62.8 years (36.1 - 85.3); 63.1% were males; 64.7% / 59.3% / 11.4% had cardiac / renal / hepatic involvement and 24.2% / 32.1% / 23.3% / 20.3% had MS I/II/III/IV. The median estimated follow up for this cohort was 69.4 months (95% CI; 64.4, 76.8) from the start of first line therapy and 45.2 months (95% CI; 36.5, 50.6) from the start of second line therapy or progression requiring treatment. The median time to second line treatment or relapse /progression mandating therapy was 16.2 months (1-93) from the start of first line therapy. At relapse, 14 patients underwent ASCT, 165 were treated with proteasome inhibitor (PI) based therapy, 83 with immunomodulator (IMiD) based therapy, 33 with alkylator based therapy, 15 with a combination of PI and IMiD, 10 with steroids, 8 with other therapies and 38 did not receive treatment. Among the 366 patients, 124 (33.9%) required change or reinstitution of therapy during follow up at the time of analysis. The median time to third line treatment or relapse /progression mandating therapy was 31 months (95% CI; 24, 40.5) from the start of second line treatment. The median overall survival (OS) was 76.4 months (95% CI; 65.2, 83.6) from the start of first line therapy and 38.8 months (95% CI; 29.6, 52.6) from the start of second line therapy. The type of therapy at relapse (ASCT vs PI vs IMiD vs melphalan vs steroids and others) did not alter the time to next therapy (ASCT, 43.1m; PI, 31m; IMiD, 37m; melphalan, 20.8m; steroids and others, 20m; p=0.3) and OS (ASCT, 66.9m; PI, 51.1m; IMiD, 51.3m; melphalan, 37.2m; steroids and others, 80.7m; p=0.9) from the start of the second line treatment; as depicted in Figure 1. Retreatment with a different drug class (as the first line treatment) at relapse significantly reduced the time to next treatment (32.3m vs 22 m; p= 0.01) as compared to same therapy; but did not have any impact on survival (30.8m vs 51.1m; p = 0.5); as presented in Figure 2. Conclusion This study provides novel information about outcomes of patients with systemic AL amyloidosis who relapse or progress after first line therapy which could be useful in planning salvage therapies and designing clinical trials. Retreatment with a different therapy at relapse improves time to next therapy but does not impact OS. Hence, we conclude that the patients can fare well post relapse/ progression and can benefit from various treatment regimens including retreatment with the same agent. Disclosures Dispenzieri: Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; pfizer: Research Funding; Alnylam: Research Funding; Celgene: Research Funding. Kapoor:Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Kumar:BMS: Consultancy; Kesios: Consultancy; Glycomimetics: Consultancy; Onyx: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; AbbVie: Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding.

scholarly journals Effective treatment of refractory acquired pure red blood cell aplasia with eltrombopag and sirolimus: a case report

2020 ◽  
Vol 11 ◽  
pp. 204062072094014
Author(s):  
Yuzhou Huang ◽  
Xianyong Jiang ◽  
Bing Han
Keyword(s):  
Cyclosporin A ◽  
Clonal Evolution ◽  
Complete Response ◽  
Pure Red Cell Aplasia ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and reduced bone marrow erythroblastic cells. For patients who are refractory to the first-line therapy (cyclosporin A with/without glucocorticoids), second-line therapy is considered less effective. We report on a patient with primary aPRCA who was refractory to cyclosporin A, glucocorticoids, and several second-line regimens. The patient was treated with sirolimus for 10 months with no improvement in hemoglobin but complete response was achieved after adding eltrombopag at a dosage of 25 mg/day. Eltrombopag was well tolerated with no evidence of clonal evolution at the end of follow up. This case provided a new attempt at treating patients with refractory/relapse aPRCA with eltrombopag, probably in combination with sirolimus.

Favorable Molecular Responses to Imatinib in CML Patients in Early Chronic Phase in Comparison to Late Chronic Phase Patients after Treatment with Hydroxyurea and Interferon.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4794-4794
Author(s):  
Frank Schüler ◽  
Malte Leithäuser ◽  
Thomas Kiefer ◽  
Saskia Richter ◽  
Gottfried Dolken
Keyword(s):  
Chronic Phase ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Transcript Levels ◽  
Log Reduction ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pre Treatment

Abstract Peripheral blood samples from 70 patients treated with imatinib were regularly sent to us for the determination of bcr-abl transcript levels by a standardized quantitative real-time PCR (TaqMan®). 45 patients with early chronic phase CML were treated with imatinib as a first line therapy and 25 patients in late chronic phase received imatinib as a second line therapy after hydroxyurea plus interferon. The median pre-treatment time with hydroxyurea plus interferon in these late chronic patients was 43 months (6 – 130). The median follow-up was 18.4 months (1–51) for first line patients and 18.0 months (1–48) for second line patients. Patients received a median dosage between 400–600 mg imatinib in both groups. At the time of diagnosis the median bcr-abl/abl ratio was 248 % (26–460%, SD: 148%) in patient receiving imatinib as a first line treatment. Patients receiving imatinib as second line treatment had a median bcr-abl/abl ratio of 24,84% (1–256%, SD: 78%) just before the imatinib treatment was initiated. Early chronic phase CML patients treated with imatinib as a first line therapy showed a strong biphasic decay of their bcr-abl transcript with a fast reduction between 1-2-log during the first 6–9 months followed by a slower rate of reduction afterwards. A bcr-abl/abl ratio &lt;0.1% could be observed in 19/51 (37%) patients and in 12/51 (23%) patients a bcr-abl/abl ratio &lt; 0.01% was found. After 18 months of therapy the median reduction of bcr-abl was about 2.5-log, after 36 months about 3-log. 12/51 (23%) patients showed a suboptimal response or had a subsequent increase of their bcr-abl transcript levels. Best responding patients could be identified by a &gt;2-log reduction after 6 months and &gt; 3-log reduction after 18 months of therapy. In late chronic phase CML patients pre-treated with hydroxyurea and interferon the overall median decrease of bcr-abl transcript levels was about 1-log after a median follow-up of 18 as well as after 36–48 months. Obviously, there are at least three subgroups of patients with a different molecular response. We identified 7/25 (28%) patients with no significant reduction of bcr-abl transcripts after 18 months as well as after 36 months of imatinib therapy. In contrast, another group of 4/25 (16%) patients showed a 2-log reduction of bcr-abl/abl ratio after 18 months with a subsequent reduction of 3-log after 36 months. Within the largest group of 14/25 (56%) patients a 1-log reduction after 18 months and a 1-2-log reduction after 36 months was observed. No patient had &gt; 3-log reduction within the whole group of 25 late chronic phase patients. The reduction of bcr-abl transcript levels as a result of imatinib therapy is significantly superior in CML patients receiving imatinib as first line treatment for CML in early chronic phase compared to patients treated with imatinib after a long term pre-treatment with hydroxyurea and interferon.

Sign in / Sign up

Export Citation Format

Share Document