Transfusion Independence in Patients with Hematologic Disorders Receiving Azacitidine Who Are Enrolled in AVIDA, a Longitudinal Patient Registry

Abstract Patients with myelodysplastic syndromes (MDS) or other hematologic disorders experience anemia and/or thrombocytopenia at some point during the course of their disease. Current management of these cytopenias includes frequent red blood cell (RBC) and platelet transfusions, and use of other supportive therapy (eg, erythropoietin). Dependence on transfusions can be coupled with diminished quality of life, poorer outcomes, and increased economic burden. Azacitidine, a hypomethylating agent approved in the US for the treatment of all 5 MDS subtypes, is associated with transfusion independence in patients enrolled in clinical trials (Silverman, et al. J Clin Oncol.2006;24:3895). The establishment of transfusion independence in patients receiving azacitidine in the non-clinical trial/community-based setting is not well characterized. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients with MDS and other hematologic disorders, including acute myeloid leukemia, who are treated with azacitidine. Baseline demographics and disease characteristics were obtained at enrollment. Transfusion requirements and onset of RBC and platelet transfusion independence were recorded. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. As of August 1, 2008, 220 (154 males, 66 females; mean age, 73.5 yrs) have been enrolled in AVIDA. At baseline, the majority of patients had primary MDS (183 patients; 83%), an ECOG performance status of 0 or 1 (164 patients; 75%), and an International Prognostic Scoring System (IPSS) risk classification of Low/Intermediate-1 (130 patients; 59%); 55 (25%) had a Intermediate-2/high IPSS risk and 35 (16%) had unknown IPSS risk. Median time from first MDS diagnosis until azacitidine treatment was 3 months (range, 0 to 149). A total of 732 cycles of azacitidine have been administered either by subcutaneous (46%) or intravenous (54%) infusion; 203 patients have received a median of 3 cycles (range, 1–15). The most common dose and schedule is 75 mg/m2 (82%) at 5 days on treatment (51%). Transfusion data are available for 136 patients who have received at least 2 cycles of azacitidine. Eighty-three of 136 (61%) patients had received at least 1 RBC transfusion during the 6 months prior to AVIDA. Of these patients, 33/83 (40%) achieved RBC transfusion independence; 23/33 (70%) first achieved RBC transfusion independence during the first 2 cycles of azacitidine therapy. Among those patients who had received a platelet transfusion 6 months prior to AVIDA, 13/22 (59%) achieved platelet transfusion independence; 11/13 (85%) first achieved platelet transfusion independence within the first 2 cycles. Azacitidine was generally well tolerated; the most common adverse events were anemia (18%), thrombocytopenia (14%), fatigue (13%), nausea (13%), constipation (12%), and neutropenia (10%). These data demonstrate that in the community-based setting, patients with MDS or other hematologic disorders can achieve transfusion independence within the first 2 cycles. The full benefit of achieving transfusion independence on quality of life and clinical outcomes will be elucidated as more patients are enrolled in AVIDA.

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Treatment of Patients with Low-Risk Myelodysplastic Syndromes Receiving Azacitidine Who Are Enrolled in AVIDA, a Longitudinal Patient Registry.

Blood ◽

10.1182/blood.v112.11.1646.1646 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1646-1646 ◽

Cited By ~ 2

Author(s):

David L. Grinblatt ◽

Mohit Narang ◽

James M. Malone ◽

David A. Sweet ◽

Tim S. Dunne ◽

...

Keyword(s):

Platelet Transfusion ◽

Performance Status ◽

Low Risk ◽

Patient Registry ◽

International Prognostic Scoring System ◽

Community Based ◽

Ecog Performance Status ◽

Transfusion Independence ◽

Risk Patients ◽

Rbc Transfusion

Abstract With the development of new agents such as azacitidine, a hypomethylating agent approved for the treatment of all 5 MDS subtypes, chemotherapy for MDS patients has become more common. Nonetheless, the use of hypomethylating agents in patients with low-risk MDS in the community-based setting has not been well characterized. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients with MDS and other hematologic disorders, including acute myeloid leukemia, who are treated with azacitidine. The characteristics and transfusion status of patients enrolled in AVIDA who had an International Prognostic Scoring System (IPSS) risk classification score of low/intermediate-1 at baseline are presented. As of August 1, 2008, 130 (91 males, 39 females) patients with an IPSS score of low/intermediate-1 have been enrolled in AVIDA; 45 (35%) with low and 85 (65%) with intermediate-1. Median age is 74.7 years (range, 41.4–91.4), and the majority (80%) had a baseline ECOG performance status of 0 or 1. Median time from first MDS diagnosis until azacitidine treatment was 7.5 months (range, 0 to 108), suggesting a delay in treatment of these patients compared with high risk patients (n = 55) in the registry (1 month). At baseline, 103/130 (79%) patients had <5% bone marrow blasts and 109/130 (84%) had a ‘good’ karyotype. Cytopenias were reported in 0 or 1 lineage for 69/130 (53%) patients and in 2 or 3 lineages for 60/130 (46%) patients; number of cytopenias at baseline is unknown for 1 (1%) patient. A total of 483 cycles of azacitidine have been administered either by subcutaneous (43%) or intravenous (57%) infusion. A total of 126 patients with an IPSS score of low/intermediate-1 have received a median of 3 cycles (range, 1 to 15); 94/126 (75%) patients have received at least 2 cycles. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. Transfusion data are available for 52 patients who were receiving RBC transfusions at baseline and have received at least 2 cycles. Of these patients, 24/52 (46%) have achieved RBC transfusion independence while receiving azacitidine; 16/24 (67%) achieved RBC transfusion independence during the first 2 cycles. Thirteen patients were receiving platelet transfusions at baseline and have received at least 2 cycles of therapy. Of those patients 8/13 (62%) have achieved platelet transfusion independence; 7/8 (88%) achieved platelet transfusion independence during the first 2 cycles. In these low-risk patients, azacitidine was generally well tolerated; the most common adverse events were anemia (20%), thrombocytopenia (13%), nausea (11%), constipation (10%), fatigue (10%), and neutropenia (10%). These data demonstrate that patients with an IPSS score of low/intermediate-1 are being treated in the community-based setting and can achieve transfusion independence while receiving azacitidine. AVIDA provides a unique opportunity to characterize the MDS patient population that is receiving chemotherapy in the community-based setting. The effect of azacitidine on the outcome and overall quality of life in this patient subpopulation will become clearer as more patients with low-risk MDS are treated.

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AVIDA: A Longitudinal Registry of Clinical and Quality of Life Outcomes in Patients with Hematologic Disorders Receiving Azacitidine.

Blood ◽

10.1182/blood.v110.11.4605.4605 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4605-4605

Author(s):

David Grinblatt ◽

Mohit Narang ◽

James Malone ◽

David Sweet

Keyword(s):

Quality Of Life ◽

Global Health ◽

Patient Registry ◽

Community Based ◽

Single Item ◽

Hematologic Disorders ◽

Patient Reported ◽

Eortc Qlq C30 ◽

Eortc Qlq

Abstract Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by ineffective hematopoiesis and peripheral cytopenias. Treatment decisions are often based on age, performance status (PS), cytopenias, International Prognostic Scoring System (IPSS) classification, and MDS subtype. Patient-reported results from a few clinical trials suggest that MDS can have a negative effect on a patient’s quality of life (QoL) with responses to treatment having a positive effect. Azacitidine (Vidaza) is a hypomethylating agent approved in the US for the treatment of MDS. In a phase III study, patients (pts) treated with azacitidine experienced significantly greater improvement in QoL compared with supportive care (Kornblith AB, et al. J Clin Oncol. 2002;20:2441). Evaluation of QoL in MDS pts treated in community-based hematology clinics is not well characterized. Azacitidine is approved for a dosing schedule of 75 mg/m2/day x 7 day q 28 days. However, the dose and schedule of azacitidine used in clinical practice varies. AVIDA is a unique, longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of pts with MDS and other hematologic disorders, including acute myeloid leukemia, who are treated with azacitidine. It aims to further the understanding of current azacitidine treatment patterns in the community, identify common care procedures and concomitant treatments, explore correlation between duration and number of treatment cycles with ongoing clinical response, and to investigate the effect of azacitidine on patient satisfaction and QoL. Patient-reported QoL will be based on the EORTC QLQ-C30 questionnaire with QoL measures obtained at baseline and at quarterly intervals for 2 years. Scores on the EORTC QLQ-C30 range from 0 to 100. Higher scores on the global health and functioning scales indicate better QoL in each measure/domain. Lower scores on the symptom and single-item scales indicate less impairment due to that symptom/single item. To date, 47 pts (34 males, 13 females; mean age, 73.2 years) with predominantly low-risk MDS have been enrolled in the registry. The majority (90%) is white and has an ECOG PS of 0 or 1. Median time from first MDS diagnosis is 2.2 months (mean, 14 months); 43 have primary and 4 have secondary MDS. IPSS is known for 36 pts; low for 8 pts, intermediate-1 for 21 pts, intermediate-2 for 6 pts, and high for 1 patient. Baseline QoL data are currently available for 42 pts. At baseline, pts reported a lower level (mean score) of global health (52), physical functioning (66) and role functioning (61) compared with cognitive (81), emotional (76), and social (71) functioning. Among the symptom/single item scales, fatigue scored the worst with a mean score of 48. Other symptom/single item scales that indicated pts were experiencing a moderate level of the measure included dyspnea (37), insomnia (29), and pain (22). Constipation (17), appetite loss (15), financial difficulties (15), and nausea/vomiting (8) were reported at lower levels. Ongoing results from this patient registry will provide insight into the QoL of pts with MDS and other hematologic malignancies in the real-world setting, and will explore any change in QoL associated with treatment and/or disease progression.

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Patients with secondary myelodysplastic syndromes (MDS) who are enrolled in AVIDA, a longitudinal registry for patients receiving azacitidine (AZA)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7094 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7094-7094

Author(s):

D. L. Grinblatt ◽

M. Narang ◽

J. M. Malone ◽

D. A. Sweet ◽

T. S. Dunne ◽

...

Keyword(s):

Treatment Duration ◽

International Prognostic Scoring System ◽

Cell Cycle Regulators ◽

Community Based ◽

Transfusion Independence ◽

Disease Characteristics ◽

Transfusion Requirements ◽

Independence Results ◽

Secondary Mds ◽

Rbc Transfusion

7094 Background: Prevalence of secondary MDS (sMDS) is increasing because of improved survival of patients treated with chemotherapy or radiotherapy and aging of the population. Methylation of cell cycle regulators is common in sMDS, thus the hypomethylating agent AZA may have a role in the treatment of these patients. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients receiving AZA. AVIDA patients with sMDS were investigated and compared with registry patients with primary MDS (pMDS). Methods: Baseline demographics and disease characteristics were obtained at enrollment. Transfusion requirements and onset of transfusion independence were recorded. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. Results: As of October 8, 2008, 23 patients with sMDS due to exposure to radioiodine (18), benzene (2), radiation (1), or other (2) have received AZA. Median time since diagnosis was 1 month versus 4 months for pMDS patients (n = 203). At baseline, patients with sMDS had a similar median age (71 yrs) compared with pMDS patients (75 yrs). However, a higher proportion of patients with sMDS had a poor-risk karyotype (44% vs. 11%), 2 to 3 cytopenias (78% vs. 52%), and an International Prognostic Scoring System (IPSS) risk score of intermediate-2/high (57% vs. 23%) compared with pMDS patients. Patients with sMDS have received 93 cycles of AZA, and as of this analysis, have received a median of 4 cycles (range, 1–13). Most common dose and schedule was 75 mg/m2 (81%), 7 days on treatment (39%) for patients with sMDS vs 75 mg/m2 (88%), 5 days on (47%) for pMDS patients. Six of 15 (40%) sMDS patients with ≥ 56 days treatment duration had received a red blood cell (RBC) transfusion during the 6 months prior to AVIDA. Of these patients, 4/6 (67%) have achieved RBC transfusion independence. Conclusions: Patients with sMDS are being treated with AZA in the community-based setting with early data demonstrating substantial benefit in transfusion independence. [Table: see text]

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Transfusion independence in patients with myelodysplastic syndromes treated with azacitidine

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6576 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6576-6576 ◽

Cited By ~ 1

Author(s):

L. R. Silverman ◽

B. L. Peterson ◽

J. F. Holland ◽

R. M. Stone ◽

B. L. Powell ◽

...

Keyword(s):

Quality Of Life ◽

Platelet Transfusion ◽

Randomized Study ◽

Phase 2 ◽

Phase 3 ◽

Beneficial Effects ◽

Transfusion Independence ◽

Transfusion Requirements ◽

Independence Results

6576 Background: Patients (pts) receiving red blood cell (RBC) transfusions are exposed to various side-effects such as intolerance reactions, iron overload, and alloimmunization risks. Reduction in RBC transfusions plus improvement in quality of life was demonstrated in pts with MDS treated with azacitidine in the phase 3 randomized study (9221) conducted by the CALGB (JCO 2002;20:2429). Azacitidine also demonstrated beneficial effects on platelets and neutrophils. To further explore transfusion results in 9221, we compared RBC and platelet transfusion requirements in pts treated with azacitidine across 3 CALGB studies (phase 2 intravenous [IV] 8421, phase 2 subcutaneous [SC] 8921, and Phase 3 SC 9221). Methods: Baseline was defined as 90 days immediately prior to randomization or crossover, as appropriate. Transfusion independence was defined as maintaining independence for ≥56 days (IWG criteria). Duration of transfusion independence was defined as the date of last transfusion to the date of the next transfusion or date of censoring. Proportions of pts who became RBC or platelet independent during the study were compared, as were the median durations of independence. Results: Compared with pts treated with IV azacitidine, a greater percent of pts treated with SC azacitidine achieved independence ( Table ), but the IV study (8421) enrolled only pts with advanced MDS. Differences of 10% in proportions of pts registered or randomized to SC azacitidine who achieved transfusion independence were noted in the phase 2 and 3 studies for RBCs (8921: 35%; 9221: 45%) and for platelets (8921: 43%; 9221: 53%). Median duration of RBC independence in 8921 was 221 days, which was within 6% of that observed for pts randomized to azacitidine in 9221 (235 days). Conclusions: These results provide further support that azacitidine has beneficial effect on erythropoiesis and thrombopoiesis. Patients with MDS treated with azacitidine may develop RBC or platelet transfusion independence. [Table: see text] [Table: see text]

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Lenalidomide for the Treatment of Low- and Int-1-Risk MDS with Del(5q): Efficacy and Quality of Life Study.

Blood ◽

10.1182/blood.v114.22.2763.2763 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2763-2763 ◽

Cited By ~ 1

Author(s):

Esther Natalie Oliva ◽

Roberto Latagliata ◽

Fortunato Morabito ◽

Antonella Poloni ◽

Riccardo Ghio ◽

...

Keyword(s):

Quality Of Life ◽

Performance Status ◽

Cytogenetic Response ◽

Study Entry ◽

International Prognostic Scoring System ◽

Ecog Performance Status ◽

Cytogenetic Abnormalities ◽

Preliminary Results ◽

Transfusion Independence

Abstract Abstract 2763 Poster Board II-739 Introduction: Chronic anemia of myelodysplastic syndromes (MDS) is associated with poor quality of life (QoL) and an inferior clinical course. Transfusion dependence in lower-risk patients is associated with reduced survival as a result of iron overload, heart failure, and progression to acute myeloid leukaemia. Lenalidomide is approved for the treatment of transfusion-dependent anemia in patients with International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk MDS with deletion 5q [del(5q)]. Rapid and durable responses include transfusion independence with a rise in Hb, suppression of the del(5q) clone, and improvement in bone marrow morphological features. We present preliminary results of a prospective single-arm trial investigating the effect on QoL, efficacy, and safety of lenalidomide in the treatment of 49 adult patients with IPSS Low- and Int-1-risk MDS with del(5q) with/without additional cytogenetic abnormalities and Hb < 10 g/dL. Methods: Exclusion criteria include: ANC < 500/mm3; PLT count < 50,000/mm3; prior chemotherapy; and ongoing treatment with rHuEpo. Lenalidomide was administered orally at a starting dose of 10 mg/day. If necessary, dosing was reduced to 5 mg/day or 5 mg on alternate days. Treatment will be continued for a maximum of 12 months or until evidence of unacceptable non-hematological adverse events, lack of response, disease progression, or relapse following erythroid improvement. QoL was assessed at study entry and weeks 8, 12, and 24 using the QOL-E v.2 questionnaire. QoL scores are standardized in a 0–100 scale with lower scores representing a worse QoL. Response was evaluated according to the modified International Working Group (IWG) response criteria. Results: Twenty patients (5 M, 15 F, mean age 72 ± 10 years) are evaluable for erythroid responses and cytogenetic changes at 12 weeks and 13 patients have reached a 24-week follow-up. At baseline, mean disease duration was 3.4 ± 2.3 years. Seventeen patients were transfusion dependent (TD), 3 were transfusion free (TF). ECOG performance status was 0 in 14 patients and 1 in 6 patients. After 12 weeks from study entry, 17 (85%) patients obtained an erythroid response with a mean Hb level increase from baseline 8.6 ± 0.9 g/dL to 11.1 ± 2.4 (p=0.001). By 24 weeks, 11 of the 13 patients re-evaluated were erythroid responders obtaining transfusion independence and significant improvements in Hb (mean change from baseline 3.7 ± 2.7 g/dL, and increase to mean 11.1 ± 2.4 g/dL (p<0.001). Eight out of 20 cases (35%) reached normal Hb levels after 12 weeks and 8 out of 13 patients (62%) by 24 weeks. A cytogenetic response (at least 50% reduction in del[5q]) was observed in 5 responders out of 13 patients evaluated at 24 weeks. Additional cytogenetic abnormalities were observed in 4 responders. A progressive improvement in QoL was experienced in responders in the first 24 weeks of treatment. Physical QoL scores increased from 35 ± 9 at baseline to 69 ± 25 at week 24 (p = 0.086). Social-QoL scores significantly changed from 29 ± 20 at baseline to 83 ± 20 at week 12 (p = 0.021). Changes in physical QoL correlated with improvements in Hb (r = 0.768, p=0.001). Drug interruption followed by reduction to 5 mg/day was required in 16 patients within the first 8 weeks due to significant neutropenia, which was associated with thrombocytopenia in 3 patients and hospitalization because of infection in 2 patients. One patient withdrew from treatment because of progressive anemia. Conclusions: Preliminary results confirm that in Low- and Int-1-risk MDS patients with del(5q) lenalidomide induces clinically significant erythroid responses and transfusion independence. Most patients require a dose reduction mainly due to neutropenia. Responders experience improvements in physical and social QoL. Disclosures: Oliva: Celgene: Consultancy. Finelli:Celgene: Consultancy.

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Tranfusion independence assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6574 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6574-6574

Author(s):

S. Anthony ◽

R. Lyons ◽

T. Cosgriff ◽

S. Modi

Keyword(s):

Life Expectancy ◽

Myelodysplastic Syndrome ◽

Multicenter Study ◽

Platelet Transfusion ◽

Dosing Schedule ◽

Transfusion Independence ◽

Performance Grade ◽

Transfusion Requirements ◽

Dosing Regimens ◽

Rbc Transfusion

6574 Background: The dosing schedule of azacitidine (75 mg/m2/day subcutaneous [SC] × 7 days, every 28 days) decreased transfusion requirements in myelodysplastic syndrome (MDS) patients in a CALGB trial by Silverman et al (JCO 2002;20:2429). Our study assessed effects on transfusion requirements in MDS patients receiving 3 alternative azacitidine dosing regimens not requiring weekend injections. Methods: This phase II, multicenter study enrolled MDS patients with any FAB subtype, life expectancy ≥7 months, and ECOG performance grade of 0–3. RA/RARS patients had to have ≥1 of the following: hemoglobin <110 g/L with transfusion need, platelet counts <100 × 109/L, or ANC <1.5 × 109/L. Patients were randomized to 1 of 3 SC regimens: AZA 5–2-2 (75 mg/m2/day × 5 days, followed by 2 days no treatment, followed by 75 mg/m2/day × 2 days), AZA 5–2-5 (50 mg/m2/day × 5 days, followed by 2 days no treatment, followed by 50 mg/m2/day × 5 days), or a 3rd regimen added later by protocol amendment: AZA 5 (75 mg/m2/day × 5 days). After 6 cycles, patients meeting International Working Group MDS response/improvement criteria (Blood 2000;96: 3671) of ≥ stable disease could continue in study for 12 more cycles. Results: In all, 75 patients (median age, 74.5 years; 61% male) are currently enrolled with 49 evaluable (completed ≥ 2 treatment cycles). To date, 12, 9, and 1 patient(s) have received ≥6 cycles of AZA 5–2-2, AZA 5–2-5, or AZA 5, respectively. RA + RARS, defined by FAB (60%) or WHO (47%), are the most common MDS subtypes. Of 24 patients, RBC transfusion dependent at baseline, 13 (54%) became independent ( Table ). Only 2 patients were platelet transfusion dependent at baseline; both became independent. After a median followup of 24 weeks, median duration of transfusion independence has not been reached. Conclusions: Treatment with azacitidine yields transfusion independence rates of 40%-60%. These preliminary results are similar across the 3 alternative doses and consistent with previous azacitidine data. [Table: see text] No significant financial relationships to disclose.

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"Huthal": A Survey of North American, Indian and Thai Hematologists Regarding Hydroxyurea Use in Thalassemia

Blood ◽

10.1182/blood.v124.21.4036.4036 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4036-4036

Author(s):

Ravi Shah ◽

Vip Viprakasit ◽

Amita Trehan ◽

Nicola A. Wright

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Clinical Practice ◽

Side Effects ◽

Thalassemia Major ◽

Hemoglobin E ◽

Positive Effects ◽

Transfusion Independence ◽

Transfusion Requirements

Abstract Background: Evidence regarding hydroxyurea (HU) effectiveness in thalassemia patients is variable and largely comes from observational studies. We suspect inconsistency in its efficacy may affect roles of HU in clinical practice worldwide. We undertook a survey of hematologists to explore the usage, effectiveness, side effects and barriers towards use of HU in clinical practice. Method: Adult and pediatric hematologists from Canada, USA, India and Thailand were surveyed by non-random sampling (snow balling). A web based survey was distributed through the Canadian hemoglobinopathy organization, ASPHO listserv, Hematology India contacts and the author’s contacts. Results: Total 112 hematologists responded [North America(82), India(24), Thailand(4), Australia(2)]. In last five years, 23% of respondents did not come across any literature regarding HU use in thalassemia. Only 18% felt that HU is effective in reducing blood transfusion (BT) requirements by ≥30% in thalassemia major(TM) in contrast to literature showing 30-80% response. Just over half of the hematologists felt HU is effective in reducing BT requirement in thalassemia intermedia(TI) and hemoglobin E/b thalassemia(HbE/bthal), in comparison to reported response of 50-100%. Drug’s ability to cause transfusion independence in TM, TI and HbE/β thal was believed by 6%, 66.3% and 46.3% of respondents, respectively, compared to literature reports of 30-70%(TM), 60-100%(TI) and 50%(HbE/β thal) transfusion independence rates with HU use(Musallam KM, et al. Blood. 2013). Half of the respondents had never tried HU in thalassemia. Major barriers towards HU use were: 1) patient refusal/fears(23%), 2)non-support by colleagues(16.8%), 3)physician concerns about side effects/cancer(14.1%), 4)compliance(11.5%), 5)funding(11.5%), 6)poor evidence(10.6%), and 7)poor physician knowledge(7%). Majority believed baseline HbF, Xmn1 polymorphism, unknown factors and β mutations to be responsible for HU effectiveness which have not been consistently reported in literature. Views regarding HU carcinogenicity were: 60%-unproven, 19%-no idea, 14%-confident about safety and 7%-proven risk. We know only 2 cases of leukemia in thalassemics on HU (a 58 year old TI patient with myeloproliferative syndrome developing AML, and a child developing leukemia within 3 months of starting HU) though a causal association could not be determined in either case. Long term data in thalassemia(13 year) and SCA(17.5 year) do not show increased risk of malignancy. Perceived monthly cost of HU therapy for an adult was $100-300 and $50-100 (40% responses each), whereas actual cost is $50-75 in Canada, $35-40 in Thailand (subsidized) and $25 in India. Of note, the approximate cost of a BT is $700 and of chelation(deferasirox) is $1400/month in Canada. Major reasons for HU discontinuation were: non-response(54%), unknown factors(37.5%), poor compliance(28.1%), cytopenias(25%), pregnancy(15.6%), hepatotoxicity(9.4%), and nephrotoxicity (7.8%). The last two have not been reported in thalassemia literature. Around 60% of physicians felt inability to adequately assess HU response. Conclusions: There is a disconnection between evidence and perceived HU response and side effects, with most hematologists underestimating the response. This could be explained by reporting bias, low utilization of HU with poor response assessment, and poor physician awareness. These factors may influence physician counselling and eventually patient’s choice and compliance, major barriers against HU use. Inconsistencies in HU use creates confusion among patients, trainees and affects comparison of disease outcomes. Improved access to HU, physician education with more acceptances of HU trials in thalassemia may increase its use. This along with systematic studies, with objective tools for functional outcomes (e.g. growth, quality of life) may help understand the true potential of HU and promote the formulation of guidelines. Being a generic drug, HU lacks commercial interest to get support for a large scale studies. If we can identify a subgroup of thalassemia patients where HU is effective, the positive effects on quality of life and the cost savings could be significant. Disclosures Off Label Use: Hydroxyurea is used in thalassemia for over two decades to reduce transfusion requirements and other purposes but its indications in thalassemia are not well recognized and accepted.. Viprakasit:Novartis: Honoraria, Research Funding; Shire co.: investigator in clinical trials, investigator in clinical trials Other.

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Clinical Evaluation of Once-Weekly Dosing of Epoetin Alfa in Chemotherapy Patients: Improvements in Hemoglobin and Quality of Life Are Similar to Three-Times-Weekly Dosing

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.11.2875 ◽

2001 ◽

Vol 19 (11) ◽

pp. 2875-2882 ◽

Cited By ~ 462

Author(s):

Janice L. Gabrilove ◽

Charles S. Cleeland ◽

Robert B. Livingston ◽

Brenda Sarokhan ◽

Eric Winer ◽

...

Keyword(s):

Quality Of Life ◽

Underlying Disease ◽

Epoetin Alfa ◽

Concomitant Chemotherapy ◽

Open Label ◽

Community Based ◽

Transfusion Requirements ◽

Clinical Benefits ◽

Chemotherapy Patients

PURPOSE: To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. PATIENTS AND METHODS: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. RESULTS: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy–Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P < .001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy. CONCLUSION: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.

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