Efficacy of Cyclosporine Treatment in Patients with MDS.

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

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.51 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 51-51

Author(s):

Xiaoyun Pan ◽

Lincy S. Lal ◽

John White ◽

Seyed Hamidreza Mahmoudpour ◽

Christian Valencia

Keyword(s):

Cervical Cancer ◽

Economic Burden ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Duration Of Treatment ◽

Second Line Therapy ◽

Treatment Regimens ◽

Line Therapy

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

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.581 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 581-581 ◽

Cited By ~ 7

Author(s):

Nizar M. Tannir ◽

Robert J. Motzer ◽

Elizabeth R. Plimack ◽

David F. McDermott ◽

Philippe Barthelemy ◽

...

Keyword(s):

Risk Groups ◽

High Dose ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

Post Hoc ◽

Study Dose ◽

Clinical Trial Information

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

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Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14107 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14107-14107

Author(s):

A. Mancuso ◽

P. Saletti ◽

S. Sacchetta ◽

E. Romagnani ◽

F. Cavalli ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Stable Disease ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Second Line Chemotherapy ◽

Line Therapy ◽

Clinical Records ◽

Line Chemotherapy

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p<0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p<0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.

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Gemcitabine in combination with oxaliplatin as second-line therapy of advanced and metastatic NSCLC

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18157 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18157-18157

Author(s):

A. J. Alencar ◽

M. Blaya ◽

L. Raez ◽

N. Farfan ◽

G. Lopes ◽

...

Keyword(s):

Organ Failure ◽

Response Rate ◽

Performance Status ◽

Single Agent ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

Multi Organ Failure

18157 Background: Single agent gemcitabine is active as second line therapy in NSCLC. Oxaliplatin may be non-cross resistant with the other platinum-containing agents used as first-line therapy in NSCLC. The combination of gemcitabine and oxaliplatin (GEMOX) is synergistic in pre-clinical models. Methods: A phase II, non-randomized trial was designed to assess the efficacy and tolerability of gemcitabine 1,000 mg/m2 over 100 min in combination with oxaliplatin 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Patients with NSCLC were eligible if they had progressed after first line treatment. Primary endpoint was tumor response rate. Planned sample size is 30 patients over a period of 2 years. Functional Assessment of Cancer Therapy- Lung (FACT-L) v.4 questionaire was used to assess quality of life of patients on therapy. Results: Twenty-two patients have been enrolled. 13 males (59%) and 9 females (41%). 15 Hispanic (68%), 4 Caucasian (18%), and 3 African-American (13%). Median age is 55 yrs. Histologic subtypes are as follows: adenocarcinoma, 12; NSCLC not otherwise specified 7; squamous cell carcinoma, 3. Nine patients had an ECOG performance status (PS) of 0 (41%) and 13 had a PS of 1 (59%). Two patients were never smokers. A total of 56 cycles have been administered (median 2, range 1 to 6). GEMOX as second-line therapy was given to 18 patients (81%), third-line to 4 patients (18%). Two patients died on study from disease progression leading to respiratory and multi-organ failure. The following Grade 3 and 4 adverse events were seen in 2 patients each: fatigue, dyspnea, anemia, and multi-organ failure. Cancer pain was seen in 1 patient. Twenty patients are available for assessment of response. Two patients had a confirmed partial response (10%) and another eight had stable disease (40%). Preliminary results of FACT-L analysis in 19 pts shows improvement in Lung Cancer Subscale (LCS) score in 25% of the patients after 2 cycles of therapy. Conclusions: Combination gemcitabine and oxaliplatin is active and well tolerated as second line treatment for NSCLC. Improvement of LCS score after 2 cycles suggests a clinical benefit that is beyond the observed response rate of 10%. No significant financial relationships to disclose.

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

Blood ◽

10.1182/blood.v120.21.1790.1790 ◽

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.

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

Blood ◽

10.1182/blood.v126.23.2125.2125 ◽

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.

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The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.2892.2892 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2892-2892

Author(s):

Claudia Crippa ◽

Samantha Ferrari ◽

Monica Drera ◽

Marinella Calarco ◽

Antonio Regazzoli ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Dose ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

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Clinical Characteristics and Long Term Outcomes of Warm Type Autoimmune Hemolytic Anemia

Blood ◽

10.1182/blood.v124.21.4874.4874 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4874-4874

Author(s):

Adisak Tantiworawit ◽

Prot Eiamprapai ◽

Sasinee Hantrakool ◽

Chatree Chai-adisaksopha ◽

Ekarat Rattarittamrong ◽

...

Keyword(s):

Response Rate ◽

Good Prognosis ◽

Line Treatment ◽

Second Line ◽

Long Term Outcomes ◽

Second Line Therapy ◽

Common Cause ◽

Line Therapy

Abstract Back ground Warm type autoimmune hemolytic anemia (AIHA) is the disease which antibody reacts with self-antigen on red blood cell. Due to the uncommon of this disease, there is a little data about long term outcomes and response to therapy especially second line treatment. Methods This is a retrospective single center study from 2002 to 2013. The diagnosis of AIHA was made by positive direct Coombs’ test with clinical hemolysis and confirmed by Hematologist. Clinical data and long term outcome were reviewed and analyzed. Results During that period, 101 patients were reviewed, 77% were female, median age was 43 (15-83) years. The median hemoglobin level at diagnosis was 5.4 (2-10) g/dl. Primary AIHA was found in 61%. The secondary causes were SLE (64%), solid malignancy (13%), lymphoma (10%), drug (8%) and infection (5%). The secondary cause from SLE was commonly found in female (96%) (P<0.001). There was the difference of age between secondary cause from SLE (<50 years) and malignancy (>50 years) (p=0.013). These results showed the interesting data that secondary cause of AIHA needed to be searching especially SLE in young female and secondary cancer in elderly patients. Not only cause could be identified but also the specific treatment needed to be given according to secondary cause. Interestingly, most patients (96%) were initially response to steroid which was not different between primary and secondary AIHA. Second line treatments were required in 33 patients (33%). The indications were steroid dependent (58%), relapse (30%) and others (12%). The second line treatments were including cyclophosphamide (52%), azathioprine (21%), cyclosporine (6%), splenectomy (6%), danazol (6%) and others (9%). The overall response rate for second line was 93%. SLE group received second line therapy more than non SLE group (p<0.001). In the light of data from this study showed that this disease had a good prognosis in both frontline steroid and second line treatment. Relapse was occurred in 50 patients (50%). Most relapse occurred > 3 years after diagnosis (58%) and more common in SLE group (p<0.001). These findings illustrated the importance nature of the disease that need long follow up due to high relapse rate around half of patients. At the median follow up 53 months, the overall survival (OS) and event free survival (relapse and death) were 84% and 48%, respectively. The independent factor for decreasing OS was age >50 years with HR 3.09 (95% CI 1.09-8.73, p=0.03) and malignancy with HR 4.06 (95% CI 1.18-13.97, p=0.03). The only significant factor for relapse is age >50 years with HR 2.08 (95% CI 1.21-3.57, p = 0.008). Twenty patients were death. The common cause of death was sepsis (30%) due to heavily immunosuppressive treatment. Conclusion AIHA has good prognosis and long term survival especially in young patient without secondary malignancy. The search for secondary cause especially malignancy is important. Most patients have responded initially to steroid and high response rate to second line therapy. The most common cause of death was sepsis which related to treatment side effect. Carefully adjust and rapid taper immunosuppressant is considerable to avoid serious complication. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Rate of Viral Re-Suppression and Retention To Care Among HIV Infected Patients on Second Line Antiretroviral Therapy at Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.

10.21203/rs.3.rs-193273/v1 ◽

2021 ◽

Author(s):

Shambel Wedajo ◽

Getu Degu ◽

Amare Deribew ◽

Fentie Ambaw

Keyword(s):

Antiretroviral Therapy ◽

Hazard Rate ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Northeast Ethiopia ◽

Line Therapy ◽

Specialized Hospital ◽

Number Of Patients

Abstract Background: In Ethiopia, first line antiretroviral therapy failure is growing rapidly. However, unlike first line therapy, to date, very little is known about the outcomes of second line therapy. Thus, this study assessed the rate of viral re-suppression and retention to care and their predictors among HIV infected patients on second line therapy. Methods: A retrospective cohort study was conducted among 642 HIV infected patients on second line therapy at Dessie Comprehensive Specialized Hospital, northeast Ethiopia from October 2016 to November 2019. Proportional Cox regression model was computed to explore predictors of viral re-suppression (Viral load less than 1000 copies/mL) and attrition to care. Results: Out of 642 subjects, 19 (3%), 44(6.9%), 70(10.9%), and 509(79.3%) patients were lost to follow up, died, transferred out, and alive on care, respectively. Similarly, 82.39 % (79.24 - 85.16%) patients had achieved viral re-suppression, with 96 per 100-person year rate of re-suppression in 550.16 year follow up. Patients who switched timely to second line therapy were at a high rate of viral re-suppression than patients who delayed to switch [Adjusted Hazard Rate, AHR = 1.43 (95%CI: 1.17-1.74)]. Not having drug substitution history [AHR =1.25 (95%CI: 1.02-1.52)] was positively associated with viral re-suppression, in contrast, being on anti-TB treatment [AHR = 0.67 (95% CI: 0.49 – 0.91)] negatively associated with viral re-suppression. By excluding transferred out cases, 63 (11%, 95% CI: 9.6 – 13.8%) out of 572 patients were failed to retain on care with 7.1 per 100 person year rate of attrition in 887.25 year observation. Patients who were ambulatory or bedridden at the time of therapy switch were more at risk of attrition to care as compared with workable patients [Adjusted Hazard Rate, AHR= 2.61 (95% CI: 1.40-4.87]. Similarly, being not virally re-suppressed [AHR= 6.87 (95% CI: 3.86-12.23)], CD4 count < = 450 cells/mm3 [AHR= 2.61 (95% CI: 1.40-4.87] were also positively associated with attrition to care. Conclusions: A significant number of patients had failed to achieve viral re-suppression and to retain on care. Most identified factors related to patient monitoring. Hence, patient centered intervention should be strengthen, besides treatment switch.

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

Therapeutic Advances in Hematology ◽

10.1177/2040620720940144 ◽

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.

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