Antithymocyte globulin has limited efficacy and substantial toxicity in unselected anemic patients with myelodysplastic syndrome

Antithymocyte globulin (ATG) has recently been popularized as an effective treatment in myelodysplastic syndrome (MDS). We treated 8 anemic MDS patients (refractory anemia [RA] and refractory anemia with excess blasts [RAEB-1]) with ATG (40 mg/kg/d for 4 days) and prednisone in a phase 2 trial. The study was stopped early according to a preset termination rule because of lack of efficacy. There were no salutary responses. Toxicities included serum sickness (in all patients), transient neutropenia and thrombocytopenia, diarrhea, vomiting, and syncope with a generalized seizure. At least 3 patients had the HLA-DR15 (DR2) allele. We conclude that the risk-benefit ratio of ATG in an unselected population of MDS patients may be unfavorable, and more work is needed to define the subset of patients who will respond to ATG before its widespread use can be recommended.

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Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial

The Lancet Oncology ◽

10.1016/s1470-2045(18)30580-1 ◽

2018 ◽

Vol 19 (12) ◽

pp. 1668-1679 ◽

Cited By ~ 75

Author(s):

Uwe Platzbecker ◽

Jan Moritz Middeke ◽

Katja Sockel ◽

Regina Herbst ◽

Dominik Wolf ◽

...

Keyword(s):

Acute Myeloid Leukaemia ◽

Myelodysplastic Syndrome ◽

Myeloid Leukaemia ◽

Residual Disease ◽

Phase 2 ◽

Open Label ◽

Multicentre Phase ◽

Phase 2 Trial ◽

Measurable Residual Disease ◽

Acute Myeloid

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Immunosuppressive Therapy for Patients With Myelodysplastic Syndrome: A Prospective Randomized Multicenter Phase III Trial Comparing Antithymocyte Globulin Plus Cyclosporine With Best Supportive Care—SAKK 33/99

Journal of Clinical Oncology ◽

10.1200/jco.2010.31.2686 ◽

2011 ◽

Vol 29 (3) ◽

pp. 303-309 ◽

Cited By ~ 113

Author(s):

Jakob R. Passweg ◽

Aristoteles A.N. Giagounidis ◽

Mathew Simcock ◽

Carlo Aul ◽

Christiane Dobbelstein ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Supportive Care ◽

Antithymocyte Globulin ◽

Group Performance ◽

Best Supportive Care ◽

Phase Iii ◽

Refractory Anemia ◽

Phase Iii Trial ◽

Hematologic Response ◽

The Impact

Purpose Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure. Patients and Methods This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration. Results Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828). Conclusion This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.

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Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial

The Lancet Diabetes & Endocrinology ◽

10.1016/s2213-8587(13)70065-2 ◽

2013 ◽

Vol 1 (4) ◽

pp. 306-316 ◽

Cited By ~ 85

Author(s):

Stephen E Gitelman ◽

Peter A Gottlieb ◽

Mark R Rigby ◽

Eric I Felner ◽

Steven M Willi ◽

...

Keyword(s):

Type 1 Diabetes ◽

Antithymocyte Globulin ◽

Phase 2 ◽

Recent Onset ◽

Onset Type ◽

Phase 2 Trial

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Azacitidine Treatment of Lenalidomide-Resistant Myelodysplastic Syndrome with Deletion 5q

Blood ◽

10.1182/blood.v118.21.2774.2774 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2774-2774 ◽

Cited By ~ 1

Author(s):

Rami S. Komrokji ◽

Najla H Al Ali ◽

Eric Padron ◽

Jeffrey E Lancet ◽

Alan F List

Keyword(s):

Myelodysplastic Syndrome ◽

Treatment Failure ◽

Effective Treatment ◽

Median Duration ◽

Research Funding ◽

Median Number ◽

Refractory Anemia ◽

International Prognostic Scoring System ◽

Cancer Center ◽

Duration Of Response

Abstract Abstract 2774 Background: Lenalidomide is a highly effective treatment for lower risk transfusion dependent myelodysplastic syndrome (MDS) patients with deletion 5q [del(5q)]. Approximately two thirds of patients become transfusion independent for a median duration of 2 years or longer (List et al, NEJM). Effective treatment alternatives after lenalidomide treatment failure are limited. We examined the response to treatment with azacitidine in del(5q) MDS patients after lenalidomide treatment failure. Methods: MDS patients with del(5q) who were treated with azacitidine after lenalidomide failure were identified through the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. Data collected included demographics, disease baseline characteristics, duration of response to lenalidomide, responses to azacitidine by international working group (IWG) 2006 criteria, transformation to acute myeloid leukemia (AML), and overall survival (OS). Descriptive statistics were used for analysis and Kaplan Meier estimates were used for OS and AML transformation. All analysis was conducted using SPSS version 19.0 statistical software. Results: Between July 2005 and June 2011, 18 del(5q) MDS patients treated with azacitidine were identified. The median age was 66 years (50–83), all patients were Caucasian, and male predominance (67%; 12 patients). ECOG performance status was 0–1 in 94% of the patients. The median duration of follow up from date of azacitidine initiation was 645 days. According to the WHO classification, 7 patients (38.9%) had MDS with isolated del(5q), 7 patients (38.9%) refractory cytopenia with multilineage dysplasia (RCMD), 2 patients (11.1%) refractory anemia with excess blasts 1 (RAEB-1), and 2 patients (11.1%) refractory anemia (RA).The international prognostic scoring system (IPSS) risk category was low in 2 (11.2%), intermediate 1 (int-1) in 14 (77.8%), and int-2 in 2 (11.2%) patients. Based on karyotype, 7 patients (38.9%) had isolated del(5 q), 9 (50%) del 5q +1 abnormality, and 2 (11.2%) with del 5q +2 or more cytogenetic abnormality. All patients were transfusion dependent. The median number of lenalidomide cycles prior to azacitidine was 12 (1–38), with median duration of response 319 days (17–1169). The median number of azacitidine cycles administered was 6 (2–23). The median duration of treatment was 183 days (43–592). The best response to azacitidine by IWG 2006 criteria was one (7.1%) complete response (CR), 2 (5.6%) marrow CR (mCR), 7 (38.9%) hematological improvement (HI), 4 (22.2%) had stable disease, and 4 (22.2%) had progressive disease (PD). The overall response rate was 56%.The HI cell lineage responses were 9 out of 18 (50%) erythroid, 3 out of 13 (23%) HI-P (Platelets), and 2 out 9 (22.2%) HI-N (neutrophils). The median OS was 749 days (95%CI 435–1063) from the time of starting azacitidine. The rate of AML transformation was 27.8% (n=5); median time to AML transformation from azacitidine start was 864 days (95%CI 360–1368). Conclusion: To our knowledge this is the first report demonstrating the activity of azacitidine in patients with del(5q) MDS after lenalidomide treatment failure. Response rates are similar to those reported in non-del(5q) patients providing azacitidine as an effective option for salvage treatment. Larger cohort of patients is needed to confirm these findings. Disclosures: Komrokji: Celgene: Honoraria, Research Funding, Speakers Bureau. Lancet:Celgene: Research Funding. List:Celgene: Consultancy.

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