Long Term Clinical Benefit of Lenalidomide (Revlimid) Treatment in Patients with Myelodysplastic Syndrome without Del 5q Cytogenetic Abnormalities.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 250-250 ◽  
Author(s):  
Azra Raza ◽  
James E. Reeves ◽  
Eric J. Feldman ◽  
H. Joachim Deeg ◽  
Luke Dreisbach ◽  
...  
Keyword(s):  
Risk Groups ◽  
Cytogenetic Response ◽  
Red Blood Cell Transfusion ◽  
Hematopoietic Stem ◽  
Vein Thrombosis ◽  
Transfusion Independence ◽  
Starting Dose ◽  
Grade 3 ◽  
Atypical Cml ◽  
Deep Vein

Abstract Background: MDSs are clonal hematopoietic stem cell malignancies characterized by cytopenias resulting from ineffective hematopoiesis. A phase 2 study of lenalidomide (MDS-002) demonstrated hematological improvement in patients with MDS without an associated deletion 5q cytogenetic abnormality (List AF, et al. Haematologica2006;91[suppl1]:379[abst 1032]). We now report multicenter results after 〉2 yrs follow-up. Methods: A total of 214 pts with transfusion-dependent anemia were categorized into the following IPSS MDS risk groups after central review of bone marrow morphology, karyotype, and peripheral blood findings: Low/Int-1 (168 [78%]); Int-2/High (8 [4%]); and unclassified (38 [18%]). Patients were unclassified for missing or inadequate marrow studies for central review (morphology [29] or cytogenetic [7]) or other diagnoses (AML [1], atypical CML [1]). Patients were evaluated for frequency and duration of red blood cell transfusion independence (RBC-TI) (IWG criteria), hemoglobin (Hgb) response, and safety. The starting dose of lenalidomide was 10 mg (daily or daily × 3 wks q28d cycle). Results: Overall, 56 (26%) of 214 enrolled patients achieved RBC-TI. Median time to RBC-TI was 5 wks, median duration of RBC-TI response was 41.0 wks (range, 8.0–136.4), and median Hgb increase achieved during RBC-TI was 3.2 g/dL (range, 1.0–9.8). An additional 36 patients experienced a ≥ 50% reduction in RBC transfusions (overall hematological improvement in 92 [43%] patients). Overall, 47 (22%) patients had an abnormal karyotype at baseline and 9 (19%) patients achieved a cytogenetic response (4 complete). The most common drug-related grade 3/4 adverse events (AEs) were neutropenia and thrombocytopenia (25% and 20%, respectively). Deep vein thrombosis occurred in only 2 (1%) patients. The duration of RBC-TI was ≥ 52 weeks in 21 (38%) patients. Among these 21 patients, 14 (67%) did not require a lenalidomide dose reduction during the first 52 weeks of treatment. Analyses of response variables will be presented. Dose-limiting neutropenia/thrombocytopenia was not reported after 52 weeks. The most commonly reported AEs after 52 weeks were mild-moderate diarrhea and fatigue (38% and 29%, respectively). Conclusion: Lenalidomide is an active, well-tolerated treatment in MDS patients with transfusion-dependent anemia that is not associated with a deletion 5q abnormality. The rate of erythroid hematologic improvement and duration of RBC-TI is encouraging and offers a possible alternative to cytokine therapy.

Rapid Control of Previously Untreated Multiple Myeloma with Bortezomib-Lenalidomide-Dexamethasone (BLD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3611-3611 ◽  
Author(s):  
Michael Wang ◽  
Kay Delasalle ◽  
Sergio Giralt ◽  
Raymond Alexanian
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Deep Vein Thrombosis ◽  
Intensive Therapy ◽  
Primary Treatment ◽  
Short Exposure ◽  
Newly Diagnosed ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Deep Vein

Abstract Introduction: Both bortezomib (B) and lenalidomide (L) are effective against relapsed/refractory and newly-diagnosed multiple myeloma (MM). The 3-drug combination of bortezomib-thalidomide-dexamethasone had induced remission in 87% of patients with untreated myeloma, significantly higher than the frequency of 66% observed with thalidomide dexamethasone. Patients and Method: We conducted a retrospective review of a pilot study in 17 previously-untreated patients with MM who were treated with bortezomib-lenalidomide dexamethasone between 4/06–4/07. Median age was 60 (35–71), median B2M was 3.7 mg/L (1.8–11.7) and median Hgb was 11 g/dl (6–14.7). Serum creatinine was greater than 2 mg/dl in one patient (6%). Bortezomib was given at 1.3 mg/m2 intravenously on days 1,4, 8 and 11; lenalidomide was at 25 mg orally daily for 21 days; and dexamethasone was at 20 mg/m2 daily orally for 4 days beginning on days 1, 9 and 17. Each cycle was 28 days. After the first cycle, a second cycle was given to 10 patients so that the median cycles of therapy was 2. As prophylaxis for deep vein thrombosis, all patients received warfarin with a targeted INR range between 2–3. All patients received daily orally vancyclovir to prevent herpes zoster. Results: Applying the Blade criteria of response (PR: greater than 50% reduction of serum myeloma protein and/or greater than 90% reduction of Bence Jones protein), remission of disease was observed in 14/17 patients (82%), including 2 patients (12%) with CR based on negative immunofixations and 12 patients (70%) with PR. All but one patient achieved remission after 1 cycle of treatment. Three patients were resistant to bortezomib-lenalidomide-dexamethasone after 2 cycles. One patient had deep vein thrombosis with pulmonary emboli. One patient had short-term grade 3 neuropathy. One patient had grade 3 thrombocytopenia and one patient had nonneutropenic pneumonia. Median nadir neutrophil count was 3000/ul (range 1400–5400/ul), and median nadir platelet count was 174 k/ul (range 38–270 k/ul). After a median 3.6 months (range 3.3–5.5), intensive therapy supported by autologous blood stem cells was given to 11 patients. Three of the 11 patients in PR after induction with bortezomib-lenalidomide-dexamethasone were converted to CR with intensification. Consequently, the CR rate after intensification 29%. Intensification is planned for the 3 patients with primary resistant MM. Discussion: Overall response and CR rates were similar to those observed previously among similar patients treated with bortezomib-thalidomide-dexamethasone. All reported primary treatment programs based on bortezomib-dexamethasone have induced high response rates of 82–92%, regardless of whether melphalan, lenalidomide, or thalidomide were included. Conclusions: One or two cycles of bortezomib-lenalidomide-dexamethasone were associated with rapid onset of response in patients with newly-diagnosed multiple myeloma. Toxicity was infrequent due to short exposure to bortezomib-lenalidomide-dexamethasone. There was early access to intensive therapy supported by autologous stem cells. Reduced exposure to drugs given as primary treatment should help preserve disease sensitivity to later treatment upon relapse.

Treatment with Imatinib in Very Elderly (> 75 Years) CML Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1096-1096
Author(s):  
Roberto Latagli Ata ◽  
Massimo Breccia ◽  
Simona Sica ◽  
Antonio Spadea ◽  
Ada D’Addosio ◽  
...  
Keyword(s):  
Late Toxicity ◽  
Cytogenetic Response ◽  
Imatinib Treatment ◽  
Very Elderly ◽  
Molecular Remission ◽  
Starting Dose ◽  
Daily Dose ◽  
Grade 3 ◽  
Early Toxicity ◽  
Complete Haematological Response

Abstract Median age of patients with CML is about 65 years, according to SEER 2000–2005 data. However, the treatment with Imatinib in elderly has been seldom specifically addressed: in particular, there is a lack of data regarding very elderly CML patients. To highlight peculiar aspects of toxicity and efficacy of Imatinib in this subset which accounts for at least 10–15% of all CML cases, we revised retrospectively 28 CML patients treated with Imatinib when aged > 75 years from 4 haematological Institution in Rome; there were 12 males and 16 females, median age at Imatinib was 78.7 years (IR 75.8 – 82.9), Sokal Risk at diagnosis was intermediate in 20 patients, high in 6 and not valuable in 2. One or more concomitant diseases requiring specific treatments were present in 26/28 patients (92.8%), with 15 patients (53.5%) assuming 3 or more concomitant drugs. Nine patients (32.1%) have been pretreated ≥ 6 months with HU before starting Imatinib; on the whole, median time from diagnosis to Imatinib was 1.8 months (IR 0.7 – 25.1). Starting dose of Imatinib was 400 mg/day in 23 patients (82.1%) and 300 mg/day in 5 patients (17.9%); overall, 15 patients (53.5%) (14/23 at 400 mg starting dose and 1/5 at 300 mg starting dose) needed a dose reduction and 6 (21.4 %) discontinued Imatinib for toxicity (early toxicity in 4 and late toxicity in 2). Excluding the 4 patients who discontinued Imatinib due to early toxicity, maximum tolerated daily dose during treatment was 400 mg in 8 patients, 300 mg in 13 patients and 200 mg in 3 patients. According to CTC-AE, grade 3 – 4 haematological and extra-haematological toxicities were observed in 7 (25%) and 12 (42.8%) patients, respectively; 2 patients (7.1%) presented a pleural effusion during Imatinib treatment. All patients were fully evaluable for response to Imatinib, with a median treatment period of 30.6 months (IR 15.7 – 49.2); six patients (21.4%) failed any response, (including 4 patients who discontinued Imatinib due to early toxicity) and 22 (78.6%) achieved a complete haematological response (CHR). Among these 22 patients in CHR, 4 refused any other karyotipic or molecular evaluation (3 are still alive in CHR, 1 died in CHR from unrelated cause after 44,5 months) and 17/18 (60.7% of all 28 patients) achieved a cytogenetic response (CyR), major in 1 patient and complete in 16 patients. In addition, 7 patients (25% of all 28 patients) achieved a complete molecular remission, with an undetectable BCR/ABL hybrid gene at qualitative nested PCR. In conclusion, Imatinib at reduced daily dose of 300 mg seems a relatively safe and quite effective treatment for very elderly CML patients; from our data, no upper age limit should be given for TKinhibitors treatment but also very elderly (and with concomitant severe diseases) patients should have this chance of cure.

Characteristics of Upper Extremity Deep Vein Thrombosis in Hospitalized Patients. a Review of 8350 Admissions from the 2012 National Inpatient Sample

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2314-2314
Author(s):  
Taeha Kim ◽  
Joseph Shatzel ◽  
Deborah L Ornstein
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Catheter ◽  
Hospitalized Patients ◽  
Catheter Placement ◽  
Red Blood Cell Transfusion ◽  
National Inpatient Sample ◽  
Central Venous ◽  
Central Venous Catheter Placement ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Background: The incidence of upper extremity deep vein thrombosis (UEDVT) is increasing due to the increased use of central venous catheters. In contrast to lower extremity DVT (LEDVT), there is limited data to guide management, with many current management recommendations based on extrapolation from LEDVT studies. The aim of this study is to evaluate the characteristics and mortality associated with hospitalized patients with UEDVT from a large national database. Methods: Using the 2012 National Inpatient Sample (NIS), admissions with the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for UEDVT (453.82) were extracted, and data collected on age, sex, length of stay, mortality, and associated diagnoses and procedures. LEDVT (ICD-9-CM 453.40) data were extracted for comparison. Collected data were used to calculate odds ratios with corresponding 95% confidence intervals and p-values to show associations where applicable. Results: Of the 7,296,968 unweighted admissions in the 2012 NIS, 8,350 were associated with UEDVT, and 18,194 were associated with LEDVT (prevalence of 0.11% vs 0.25%, respectively). UEDVT and LEDVT rates were similar in men and women. However, compared to LEDVT, patients with UEDVT were younger (61yr vs. 67 yr; p<0.0001), had longer mean LOS (14 days (range 0-309) vs. 5 days (range 0-345); p<0.0001), and higher inpatient mortality (7.75% vs 5.34%; OR 1.45, 95% CI 1.31, 1.61; p<0.0001). Pulmonary embolism was less common in UEDVT than in LEDVT (6.2% vs. 25%; OR 0.24, 95% CI 0.22, 0.27; p<0.0001), but significantly more common than the general hospitalized population (6.2% vs. 0.08%; OR 7.7, 95% CI 7.04, 8.42; p<0.0001). Malignancy was slightly more common in patients with UEDVT compared to those with LEDVT (30.1% vs 27.1%; OR 1.11, 95% CI 1.05, 1.17; p=0.0002). UEDVT was associated with central venous catheter placement (OR 10.1, 95% CI 9.56, 10.68; p<0.0001), other venous catheter placement (OR 21.9, 95% CI 20.9, 22.9; p<0.0001), and red blood cell transfusion (OR 3.6, 95% CI 3.47, 3.83; p<0.0001) in the hospitalized population. Procedures most commonly associated with LEDVT were interruption of the vena cava, red blood cell transfusion and other venous catheter placement. Conclusions: UEDVT was less common than LEDVT, and associated with central venous catheter placement and blood transfusions in hospitalized patients. UEDVT tended to occur in younger patients with longer LOS, and was associated with a higher mortality and a slightly higher prevalence of malignancies than LEDVT. PE was less common during admissions with UEDVT than LEDVT, however UEDVT admissions were associated with an increased incidence of PE compared to the general inpatient population. The results of this large epidemiologic study of UEDVT in hospitalized patients contribute to our understanding of this increasingly common disease and will help define strategies for prophylaxis and treatment. Disclosures No relevant conflicts of interest to declare.

Safety and pharmacokinetics (PK) of AMG 706 in combination with gemcitabine for the treatment of patients (pts) with solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14005-14005 ◽  
Author(s):  
T. J. Price ◽  
L. Lipton ◽  
J. Williams ◽  
J. McGreivy ◽  
S. McCoy ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Vein Thrombosis ◽  
Finding Study ◽  
Label Dose ◽  
Grade 3 ◽  
Deep Vein

14005 Background: AMG 706 is an oral, investigational multikinase inhibitor (MKI) with antiangiogenic and direct antitumor activity achieved by selectively targeting VEGF, PDGF and Kit receptors. Methods: This is a fully enrolled, phase 1b, open-label, dose- finding study. The objectives are to determine the maximum tolerated dose and to assess safety and PK of AMG 706 in pts with solid tumors receiving AMG 706 plus gemcitabine. Pts =18 years with ECOG 0–2 and no prior treatment with bevacizumab or VEGFr MKIs were assigned to cohorts receiving escalating doses of AMG 706 (50mg QD, 125mg QD or 75mg BID continuously from day 2 of cycle 1) plus gemcitabine (1000mg/m2 weekly for 7/8 wks, then 3/4 wks per cycle) for up to 11 cycles. Assessments include dose-limiting toxicities (DLT) (weeks 1–4) and tumor response (every 3 months). Results: 26 pts were enrolled and received at least 1 dose of AMG 706 (50mg QD n=11; 125mg QD n=6; 75mg BID n=9). All but 2 pts have completed the study. Median (range) age was 57 (25–77) yrs. 65% of pts received prior chemotherapy; 4 pts received prior gemcitabine (50mg QD n=2; 125mg QD n=1; 75mg BID n=1). There were 2 DLTs: grade 4 neutropenia (125mg QD), grade 3 deep vein thrombosis (75mg BID). Treatment-related adverse events (AE) occurring in = 10% of pts are shown in the table . The mean AMG 706 PK profiles were not markedly different when AMG 706 was dosed on the same day or 24 hours after gemcitabine administration. Objective tumor responses per RECIST for 26 evaluable pts were: 2 unconfirmed PR (50mg QD n=1; 125mg QD n=1), 7 SD (50mg QD n=3; 125mg QD n=1; 75mg BID n=3), 11 PD (50mg QD n=7; 125mg QD n=3; 75mg BID n=1), and 6 not available (125mg QD n=1; 75mg BID n=5). Conclusions: These preliminary data suggest that, in pts with solid tumors, AMG 706 combined with gemcitabine had an expected AE profile at the target once-daily dose of 125mg QD, with little effect on AMG 706 PK. The data provide a foundation for conducting further trials, potentially including biliary tumors. Final data will be presented. [Table: see text] No significant financial relationships to disclose.

Clinical benefit of luspatercept in patients (pts) with lower-risk MDS (LR-MDS) and high transfusion burden in the phase III MEDALIST study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7554-7554
Author(s):  
Amer Methqal Zeidan ◽  
Guillermo Garcia-Manero ◽  
Amy Elizabeth Dezern ◽  
Pierre Fenaux ◽  
Peter L. Greenberg ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Treatment Options ◽  
Unmet Need ◽  
Secondary Analysis ◽  
Phase Iii ◽  
Transfusion Independence ◽  
Starting Dose ◽  
Clinically Significant ◽  
Grade 3 ◽  
Rbc Transfusion

7554 Background: Anemic pts with LR-MDS and high baseline RBC transfusion burden (HTB) have very few treatment options and constitute a pt population with significant clinical unmet need. In this secondary analysis of the MEDALIST trial (NCT02631070), we sought to evaluate the clinical benefit of luspatercept in this pt population. Methods: MEDALIST is a randomized, placebo (PBO)-controlled, phase 3 study evaluating the efficacy and safety of luspatercept in pts with anemia due to LR-MDS with ring sideroblasts (RS) (Fenaux & Platzbecker et al. NEJM. 2020;382:140-51). Pts were aged ≥ 18 years; had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS; were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents (serum erythropoietin > 200 U/L); and had anemia requiring regular RBC transfusions (≥ 2 units/8 weeks in the 16 weeks prior to randomization). 229 pts were randomized 2:1 to luspatercept (starting dose 1.0 mg/kg; titration up to 1.75 mg/kg allowed) or PBO subcutaneously every 3 weeks. HTB was defined as ≥ 6 RBC units transfused/8 weeks. Results: 153 pts were randomized to luspatercept and 76 to PBO. As of July 1, 2019, 23/66 (34.8%) and 12/66 (18.2%) HTB pts receiving luspatercept achieved a ≥ 50% and ≥ 75% reduction from baseline in RBC transfusion burden over ≥ 24 weeks, respectively, vs 3/33 (9.1%; P = 0.0063) and 1/33 (3.0%; P = 0.0363) pts receiving PBO. 6/66 (9.1%) luspatercept-treated HTB pts and 1/33 (3.0%) PBO-treated HTB pt achieved RBC-transfusion independence (TI) ≥ 8 weeks in Weeks 1–24 ( P = 0.2699). The median (range) time to achieve RBC-TI with luspatercept was 50.0 days (1.0–100.0) and median (range) duration of RBC-TI in the luspatercept arm was 42.6 weeks (8.4–81.1). Mean number of transfusion events in Weeks 1–24 was 9.2 in the luspatercept arm vs 12.4 in the PBO arm (hazard ratio [95% confidence interval] 0.794 [0.660–0.956]). 65/66 (98.5%) luspatercept- and 29/33 (87.9%) PBO-treated HTB pts reported ≥ 1 treatment-emergent adverse event (TEAE); 11/66 (16.7%) and 3/33 (9.1%) pts, respectively, reported ≥ 1 TEAE leading to discontinuation. 28/66 (42.4%) luspatercept- and 15/33 (45.5%) PBO-treated pts reported ≥ 1 serious AE. Incidence of grade 3–4 TEAEs in HTB pts was similar between arms (53.0% luspatercept vs 54.5% PBO). Conclusions: Luspatercept treatment resulted in clinically significant reductions in transfusion burden and reduced number of transfusion events in HTB pts with LR-MDS with RS, with an acceptable safety profile consistent with the overall population. Clinical trial information: NCT02631070 .

scholarly journals Incidence of deep vein thrombosis and quality of venous thromboembolism prophylaxis

2014 ◽  
Vol 41 (1) ◽  
pp. 02-06 ◽  
Author(s):  
Alberto Okuhara ◽  
Túlio Pinho Navarro ◽  
Ricardo Jayme Procópio ◽  
Rodrigo De Castro Bernardes ◽  
Leonardo De Campos Correa Oliveira ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
High Risk ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Risk Groups ◽  
Moderate Risk ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
Very High

OBJECTIVE: to determine the incidence of deep vein thrombosis and prophylaxis quality in hospitalized patients undergoing vascular and orthopedic surgical procedures. METHODS: we evaluated 296 patients, whose incidence of deep venous thrombosis was studied by vascular ultrasonography. Risk factors for venous thrombosis were stratified according the Caprini model. To assess the quality of prophylaxis we compared the adopted measures with the prophylaxis guidelines of the American College of Chest Physicians. RESULTS: the overall incidence of deep venous thrombosis was 7.5%. As for the risk groups, 10.8% were considered low risk, 14.9%moderate risk, 24.3% high risk and 50.5% very high risk. Prophylaxis of deep venous thrombosis was correct in 57.7%. In groups of high and very high risk, adequate prophylaxis rates were 72.2% and 71.6%, respectively. Excessive use of chemoprophylaxis was seen in 68.7% and 61.4% in the low and moderate-risk groups, respectively. CONCLUSION: although most patients are deemed to be at high and very high risk for deep vein thrombosis, deficiency in the application of prophylaxis persists in medical practice.

Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6504-6504 ◽  
Author(s):  
Andreas Hochhaus ◽  
Neil P. Shah ◽  
Jorge E. Cortes ◽  
Michele Baccarani ◽  
M. Brigid Bradley-Garelik ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Cytogenetic Response ◽  
Transformation Rate ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Intent To Treat

6504 Background: In the phase 3 DASISION trial of dasatinib v IM in patients (pts) with newly diagnosed CML-CP, dasatinib had higher 12-month rates of complete cytogenetic response (CCyR) and major molecular response (MMR) (Kantarjian, NEJM 2010;362:2260). By 12 months confirmed CCyR (cCCyR) rates for dasatinib v IM were 77% v 66%, P=0.001, meeting the primary endpoint. Methods: Pts were randomized to receive dasatinib 100 mg once daily (QD; n=259) or IM 400 mg QD (n=260). Results: Minimum 24-month follow-up (median 26.6 months) is reported here. 24-month molecular response rates were higher for dasatinib v IM: MMR (BCR-ABL ≤0.1%) 64% v 46%, P<0.0001; MR4 (BCR-ABL ≤0.01%) 29% v 19%, P=0.0053; MR4.5 (BCR-ABL ≤0.0032%) 17% v 8%, P=0.0032. MMR rates were higher for dasatinib in all Hasford risk groups (high 73% v 56%; intermediate 61% v 50%; low 73% v 56%). Of pts who achieved MMR at 12 months, on dasatinib v IM, 97% v 92% had maintained their MMR at 24 months, respectively. Pts receiving dasatinib v IM had faster responses; median time to CCyR and MMR was 3.2 v 6.0 and 15 v 36 months, respectively. In an intent-to-treat analysis, fewer pts receiving dasatinib (n=9; 3.5%) transformed to accelerated/blast phase v IM (n=15; 5.8%) on study or during follow-up after discontinuation. 24-month overall and progression-free survival were similar for dasatinib v IM: 95.4% v 95.2% and 93.7% v 92.1% (follow-up is ongoing). Few additional adverse events (AEs) were reported between 12 and 24 months in both arms, with grade 3/4 nonhematologic AE rates ≤1%. In each arm, 10 pts had a BCR-ABL mutation detected at time of discontinuation. For dasatinib v IM, 23% v 25% discontinued treatment for drug-related AEs (7% v 5%), progression (5% v 7%), failure (3% v 4%), unrelated AEs (2% v <1%), death (2% v <1%), and other (4% v 8%). Few pts discontinued between 12 and 24 months for dasatinib (n=19; 7%) and IM (n=16; 6%). Conclusions: Updated data with minimum 36-month follow-up will be presented, including mutation analyses in pts who discontinued, progressed, or had suboptimal response. Pts receiving dasatinib had a lower transformation rate and higher molecular responses v pts receiving IM, supporting the use of dasatinib in newly diagnosed CML-CP.

Therapy of Early Stage Myelodysplastic Syndrome (MDS) with Anti-Thymocyte Globulin (ATG) and Etanercept.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1462-1462
Author(s):  
Bart L. Scott ◽  
Aaron L. Holsinger ◽  
Aaravind Ramakrishnan ◽  
Barry Storer ◽  
Pamela S. Becker ◽  
...  
Keyword(s):  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Red Blood Cell ◽  
Early Stage ◽  
Pilot Trial ◽  
Risk Groups ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Phase 2 Trial ◽  
Soluble Tnf Receptor

Abstract Immunosuppressive therapies have proven valuable in treating ineffective hematopoiesis in patients with Myelodysplastic Syndrome (MDS). Following an encouraging pilot trial, we evaluated the combination of equine anti-thymocyte globulin (ATGAM) and the soluble TNF receptor etanercept in a phase 2 trial. So far 23 patients with MDS (6-RA, 4-RARS, 12-RCMD, 1-RAEB-1) in IPSS risk groups low (n=8) or intermediate-1 (n=15) have been enrolled. All patients were platelet or red blood cell transfusion dependent. Nineteen patients completed therapy with I.V. ATGAM at 40mg/kg/day for four consecutive days, followed by etanercept, 25mg s.c. twice a week for 2 weeks every month for 4 months. The regimen was well tolerated and the majority of adverse events were anticipated infusional reactions related to ATGAM administration. Responses were assessed by modified International Working Group criteria. Twelve patients had hematological improvement (HI)-erythroid, 2 HI-neutrophil, and 3 HI-platelet. Five patients achieved red blood cell and one patient platelet transfusion independence. There was one complete remission in a patient with a co-existing diagnosis of multiple sclerosis. Thus, the overall response rate by intent to treat analysis among the 23 patients was 61%. Four patients did not complete their first course of therapy due to anaphylactic reaction, thrombosis of a pre-existing femoral graft, myocardial infarction, and patient preference. Among patients who completed treatment 74% had a hematological response, with duration of at least 5 months. Combination therapy with ATG and etanercept was active and safe in unselected patients with low and intermediate-1 risk MDS.

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