Original Study
Treatment of Patients With Myelodysplastic Syndrome With Lenalidomide in Clinical Routine in Austria Gregor Aschauer,1 Richard Greil,2 Werner Linkesch,3 Thomas Nösslinger,4 Richard Stauder,5 Sonja Burgstaller,6 Michael Fiegl,7 Michael Fridrik,8 Michael Girschikofsky,9 Felix Keil,10 Andreas Petzer1 Abstract Since the MDS-004 trial, a double-blind, phase 3 study, published in 2011, lenalidomide has shown efficacy in lower-risk myelodysplastic syndrome (MDS) patients with the del(5q) cytogenetic abnormality. We here show the results of 50 Austrian MDS patients who received lenalidomide, and the data support its use in lower-risk MDS patients in clinical practice. Background: Lenalidomide has demonstrated remarkable efficacy for therapy of lower-risk myelodysplastic syndromes (MDS) associated with 5q. The present evaluation aimed to describe the characteristics and outcomes of low-risk MDS patients treated with lenalidomide in Austria. Patients and Methods: For this retrospective, multicenter, observational analysis of MDS patients who received lenalidomide, data were collected at various hospitals in Austria over a period of 3 years. MDS classification, previous and current MDS therapies, and outcome and safety of lenalidomide were evaluated. Results: Forty-six percent of the patients (n ¼ 23) had a 5q syndrome, while 12% (n ¼ 6) exhibited 5q plus additional aberrations or isolated 5q but 5% blasts in the bone marrow (10%, n ¼ 5). The remaining 32% of patients (n ¼ 16) had MDS with other World Health Organization classifications. Seventy percent belonged to lower International Prognostic Scoring System risk classes. Sixteen centers participated, involving a total of 50 patients. Most frequently used lenalidomide doses were 10 mg and 5 mg on days 1 to 21 of a 28-day cycle. Seventy-five percent of the patients received 11 months of treatment, with a median therapy period of 3.5 months; median follow-up was 3.9 months (range, 0-26 months). Response rate, defined as transfusion independence during the 2 months after lenalidomide therapy, was 64%. Median overall survival was not reached. Conclusion: Lenalidomide was well tolerated and is an effective and well-tolerated option for therapy of patients with 5q syndrome but also lower-risk MDS patients with other World Health Organization classifications in clinical practice. Clinical Lymphoma, Myeloma & Leukemia, Vol. 15, No. 11, e143-9 ª 2015 Elsevier Inc. All rights reserved. Keywords: 5q deletion, Lenalidomide, MDS clinical practice, Myelodysplastic syndromes
Introduction The immunomodulating drug lenalidomide exerts its therapeutic effect in patients with myelodysplastic syndromes (MDS) via a dual mechanism: it suppresses 5q progenitors and supports effective 1 Internal Medicine I, Medical Oncology, Hematology and Gastroenterology, Bamherzige Schwestern Hospital, Linz, Austria 2 Department of Internal Medicine III, Hospital Salzburg—Paracelsus Medical University, Salzburg, Austria 3 Department of Hematology and Oncology, Medical University of Graz, Graz, Austria 4 Department of Hematology and Oncology, Hanusch Hospital, Vienna, Austria 5 Department of Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria 6 Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria 7 Department of Medical Oncology, Hospital Natters, Natters, Austria 8 Department of Hematology and Oncology, General Hospital Linz, Linz, Austria
2152-2650/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2015.07.645
erythropoiesis in MDS clones without a 5q deletion.1-3 Erythroid response rates of up to 67% and cytogenetic response rates of up to 73% have been reported, as well as sustained transfusion independence in patients with complete cytogenetic remission.4,5 9
Department of Hematology and Oncology, Elisabethinen Hospital Linz, Linz, Austria Department of Hematology and Oncology, Hospital Leoben, Leoben, Austria
10
Submitted: Jun 12, 2015; Revised: Jul 16, 2015; Accepted: Jul 28, 2015; Epub: Aug 05, 2015 Address for correspondence: Andreas Petzer, MD, Internal Medicine I, Medical Oncology, Hematology and Gastroenterology, Barmherzige Schwestern Hospital Linz, Seilerstaette 4, 4010 Linz, Austria Fax: þ43 732 7677 7139; e-mail contact:
[email protected]
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Treatment of MDS in Austria Despite these facts and the promising outcome data, lenalidomide was not approved for therapy of these patients in Austria and most other European countries until June 2013. Reasons that accounted for the decision of the European Medicines Agency (EMA) against immediate approval were that (1) the pivotal study for product approval in the United States was a single-arm phase 2 study,6 (2) there was concern regarding progression to acute myeloid leukemia (AML) in the absence of a comparator arm, and (3) long-term data on the use of lenalidomide in this group of patients were not available at that time. In 2011 a randomized controlled trial on lower-risk MDS patients with a 5q deletion has been published fulfilling most of these requirements, including longer-term follow-up data.5 The aim of the present study was to evaluate the characteristics of MDS patients who had actually received lenalidomide. By means of a questionnaire, general patient characteristics, cytogenetic status, and risk class according to International Prognostic Scoring System (IPSS) as well as treatment modalities were evaluated to identify the principles guiding Austrian physicians in their decision to use lenalidomide for treatment of MDS. A special focus of the analysis was on the safety of lenalidomide in terms of progression to AML. Finally, we wanted to investigate whether high response rates comparable to those reported in clinical studies could also be achieved with lenalidomide in a real-life situation in clinical practice.
Patients and Methods Study Design and Patients REALM (REtrospective Analysis of Local treatment in MDS) was a retrospective, multicenter, observational analysis of patients receiving lenalidomide for therapy of MDS in clinical practice in Austria. All general and teaching hospitals in Austria were invited to participate. Medical records of consecutive MDS patients that had received at least 1 cycle of lenalidomide between Q3/2006 and Q2/ 2009 were obtained and used for data collection. No other inclusion or exclusion criteria had to be taken into account. The observational period was the time of treatment with lenalidomide; the follow-up period was at the discretion of the treating physicians. The study was approved by local ethics committees. Data collection was in accordance with privacy law requirements.
Data Collection A questionnaire was sent out to all general hospitals and university hospitals in the country (n ¼ 30) that used lenalidomide for therapy of MDS. Sixteen centers participated, and a total of 50 questionnaires were returned. Baseline details collected included patient characteristics: age, weight, height, sex, Eastern Cooperative Oncology Group (ECOG) performance status, comorbidities and Charlson comorbidity index (CCI), ferritin serum levels, and iron chelation therapy; MDS diagnosis and classification: date of diagnosis, cytogenetic parameters, classification according to FrencheAmericaneBritish (FAB)7 and World Health Organization (WHO) classification,8 and IPSS at diagnosis9; previous MDS therapies: antineoplastic therapies, red blood cell transfusions (RBCT), erythropoiesis-stimulating agents, and stem cell transplantation. During lenalidomide treatment, data collection per cycle included MDS and concomitant therapies (dose, frequency, dose delay and/or reduction, duration): lenalidomide, RBCT, antithrombotic prophylaxis, antibiotics,
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erythropoiesis-stimulating agents, granulocyte-colony stimulating factors, and iron chelation therapy; laboratory parameters (weekly): complete blood count including minimal absolute neutrophil count (ANC), serum creatinine and erythropoietin, urea, and C-reactive protein. In addition, ECOG performance status and adverse events per cycle had to be documented. If data were incomplete, these parameters were excluded from the analysis. Because our analyses were initiated in 2006, the WHO classification for MDS of 20018 was used in the present study. In contrast to the current classification10, the 2001 WHO classification recognized the 5q syndrome as a separate entity that was defined by the following parameters: primary MDS, 5q as the only karyotypic abnormality, and < 5% blasts in blood and marrow.
Study Objectives and Outcome Parameters The primary aim of the study was to evaluate patterns of use of lenalidomide in MDS patients in the clinical routine in Austria. Relevant information was derived from the parameters listed above in MDS and concomitant therapies. In addition, effectiveness and safety of lenalidomide were evaluated. Outcome and safety parameters assessed were direct parameters such as clinical response in terms of transfusion independence, cytogenetic response (if performed), overall survival (OS), and hematologic toxicities. Furthermore, surrogate parameters such as dosing and duration of lenalidomide therapy including number of cycles and reasons for discontinuation of therapy were documented. In addition, patients were divided into 4 subgroups according to the WHO classification from 20018 to determine the impact of the underlying type of MDS on the above-listed parameters: (1) 5q syndrome, (2) MDS with a deletion of 5q and additional aberrations, (3) MDS with a deletion of 5q as a single aberration (but 5% blasts in the bone marrow [BM]), and (4) all other MDS.
Statistical Analysis Statistical analysis was descriptive in nature.
Results Baseline Characteristics Of the 30 invited centers, 16 participated involving a total of 50 patients in the study. Baseline characteristics are listed in Table 1. In general, the performance status of patients was good (73% of all patients, ECOG performance status 0 to 1) and the CCI score was low (90% of all patients, CCI 0 to 3). Most commonly specified comorbidities were congestive heart failure (n ¼ 9), renal insufficiency (n ¼ 8), venous thromboembolism (n ¼ 8), diabetes (n ¼ 7), and solid tumors (n ¼ 6). About half of the patients had a 5q syndrome (46%), while only minor proportions exhibited 5q plus additional aberrations (12%) or isolated 5q but 5% blasts in the BM (10%) (Table 2). The remaining patients had MDS with other WHO classifications. The disease had already progressed to AML in 2 patients at study entry, one with 5q plus additional aberrations and the other with isolated 5q. This distribution pattern was reflected in the IPSS distribution: low risk and intermediate-1 patients accounted for 70% of the patients, while only 22% were graded as intermediate-2 or high risk (Table 2). In 4 patients (8%), the IPSS was not evaluable. Eight patients had received previous hematologic or specific MDS therapies involving azacitidine, cytarabine, HAM (high-dose ara-C,
Gregor Aschauer et al Lenalidomide Therapy Modalities and Outcome
Table 1 Baseline Patient Characteristics Characteristic
Value
No. patients (no. female)
50 (33)
Age (years), median (range)
74 (42-88)
ECOG Performance Status (n [ 47), n (%) 0
14 (30)
1
20 (43)
2
10 (21)
3
3 (6)
CCI Score (n [ 50), n (%) 0-3
45 (90)
4-8
5 (10)
Comorbidities,a n Congestive heart failure
9
Renal insufficiency
8
Venous thromboembolism
8
Diabetes
7
Solid tumor
6
Lymphoma, multiple myeloma
5
Cerebrovascular diseases
5
Leukemia
4
Peripheral vascular disease
3
Dementia
2
Chronic lung disease
2
Myocardial infarction
1
Abbreviations: CCI ¼ Charlson comorbidity index; ECOG ¼ Eastern Cooperative Oncology Group. a Multiple selections per patient possible.
mitoxantrone), hydroxyurea, anagrelide (n ¼ 5), and allogeneic stem cell transplantation (n ¼ 3). Within 4 weeks before starting lenalidomide therapy, 38 patients had received RBCT, with the lowest rate in patients with 5q syndrome (evaluated patients, n ¼ 18; median number of RBCT, 4.0; range, 2-12), increasing numbers of RBCT in patients with 5q and additional aberrations (evaluated patients, n ¼ 3; RBCT, 6.5; range, 2-9), and isolated 5q with 5% blasts in the BM (evaluated patients, n ¼ 3; RBCT, 6.0; range, 2-8), and the highest numbers in patients with “other MDS” (evaluated patients, n ¼ 11; RBCT, 8.0; range, 2-14).
Across all MDS groups, 54% of all physicians provided a lenalidomide dose of 10 mg/day and 40% provided a lower dose of 5 mg/day (Table 3). With one exception, the administration schedule was lenalidomide daily on days 1 to 21 of repeated 28-day cycles. In the total population, the median therapy period was 3.5 months; median follow-up was 3.9 months (range, 0-26 months). In patients with 5q syndrome, the period of lenalidomide therapy was considerably longer (median, 10 cycles and 9.6 months) compared to all other groups of patients (Table 3, Figure 1). Median follow-up in 5q syndrome patients was 4.7 months (range, 0-17 months). The rate of RBCT independence (100%) during a period of 2 months was 64%. Rates were comparable in all 4 MDS subgroups (range, 50%-80%, Table 4). The 2 patients who had already progressed to AML at study entry did not exhibit any response to lenalidomide therapy. Of the remaining 48 MDS patients, 11 developed AML (Table 5): 6 of these had a 5q syndrome or an isolated 5qdeletion with 5% BM blasts; 5 belonged to the groups 5q plus additional aberrations or other MDS. Median time from diagnosis to the onset of AML for all transformed patients was 15 months and for patients with 5q syndrome was 62 months. Median OS was not reached in the observation period (Figure 2A). The survival plot depicting the OS of the 4 WHO subgroups (Figure 2B) indicates a superior survival for MDS patients with a 5q syndrome or an isolated 5q but 5% BM blasts compared to the other 2 MDS subtypes. The main reason for discontinuation of lenalidomide therapy was disease progression (n ¼ 16), while cytopenia—the most limiting toxicity of lenalidomide—caused discontinuation in only 2 patients. In another 4 patients, lenalidomide was discontinued as a result of physicians’ decisions after the achievement of transfusion independence.
Safety In general, lenalidomide was well tolerated. As expected, cytopenias were the most common adverse events. Median nadirs of ANC and platelets were 0.6 109/L and 56 109/L, respectively; for ANC and platelets, nadirs were reached after 28 days and 54 days, respectively, after initiating lenalidomide. Two patients discontinued lenalidomide therapy because of cytopenia. Allergic reactions were seen in 2 patients. Infections or renal insufficiencies were rare during therapy.
Table 2 MDS Classification According to WHO 2001 and IPSS at Diagnosis Classification WHO classification, n (%)
5q
L
Syndrome 23 (46)
5qL Plus Other Aberrations
Isolated 5qL (Blasts ‡5%)
Other MDS
Total
6 (12)
5 (10)
16 (32)
50 (100)
IPSS, n (%) Low
13 (26)
0 (0)
0 (0)
3 (6)
16 (32)
Int-1
9 (18)
2 (4)
1 (2)
7 (14)
19 (38)
Int-2
0 (0)
2 (4)
3 (6)
3 (6)
8 (16)
High
0 (0)
2 (4)
1 (2)
0 (0)
3 (6)
Unknown
1 (2)
0 (0)
0 (0)
3 (6)
4 (8)
Abbreviations: Int ¼ intermediate; IPSS ¼ International Prognostic Score System; MDS ¼ myelodysplastic syndromes; WHO ¼ World Health Organization.
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Treatment of MDS in Austria Table 3 Lenalidomide Dosing and Number of Cycles in MDS Subgroups According to WHO 2001 Classification and Total Population Characteristic
5qL Syndrome (n [ 23)
5qL D Additional Aberrations (n [ 6)
5qL Isolated With ‡5% BM Blasts (n [ 5)
Other MDS (n [ 16)
Total (n [ 50)
Dose (Median), mg/daya 2.5b
1
0
0
0
1
5
9
2
2
7
20
10
13
4
3
7
27
15
0
0
0
1
1
20 Cycles (median)
0
0
0
1
1
10
3
4
2.5
4.5
Abbreviations: MDS ¼ myelodysplastic syndrome; WHO ¼ World Health Organization. a Days 1 to 21 of repeated 28-day cycles. b Five milligrams every second day.
Discussion The aim of the present study was to characterize the patient population already receiving lenalidomide in Austria and to analyze treatment modalities, outcome, and safety of the lenalidomide therapy. The median age in our population was 74 years, which reflects the typical age distribution of MDS patients.11 The proportion of patients with a favorable ECOG performance status and CCI was high, and the proportion of patients having received previous hematologicspecific MDS therapies was low (16%). The majority of patients had received RBCT within the last 4 weeks before the initiation of therapy (76%). Hence, physicians tended to use lenalidomide in MDS patients with a good prognosis according to karyotype and IPSS and in patients who had received only few MDS-specific pretreatments. The use of lenalidomide in MDS patients was most comprehensive and most promising for lower-risk MDS patients with 5q aberrations.4,5 The fact that several physicians still provided lenalidomide in MDS/non-5q patients is, however, attributable to lack of active treatments for lower-risk MDS patients. Across all MDS groups, the most widely prescribed dose (> 50% of prescribing physicians) was the one recommended by the US investigators: 10 mg/day. Another 40% were provided a lower dose of 5 mg/day. With the exception of 1 patient (5 mg every second day), the dosing schedule was lenalidomide for 21 days every 4 weeks. One nonrandomized4 and 1 randomized controlled trial5 on low and intermediate-1 risk MDS/5q (with and without additional cytogenetic abnormalities) both used this dosing schedule (5 or 10 mg lenalidomide, respectively, for 21 days every 4 weeks with superior results with 10 mg for 21 days every 4 weeks).5 Austrian physicians subsequently adhered to this administration protocol. In the total population, the median rate of RBCT independence was 64% (range over the 4 subgroups, 50%-80%) in the present study. Although our population was very heterogeneous (Table 2) and therefore differed from those in other studies, this rate is very much in accordance with published data. In 2 other studies, a randomized controlled trial5 and an observational study conducted in France,12 on low and intermediate-1 risk 5q MDS patients, both with a high proportion of isolated 5q patients in their populations, 61% and 63% of all patients reached transfusion independence. Similar rates (67%) were achieved by List et al4 in 2006 in 5q patients of all IPSS risk classes.
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However, the short median follow-up period in our study (3.9 months) does not allow us to draw any definite conclusions regarding OS. Nevertheless, our data reveal a superior survival in MDS patients with 5q syndrome and 5q as a single aberration compared to the other 2 MDS subtypes (5q plus additional aberrations and other MDS; Figure 2). This is in contrast to a study from Fenaux et al,5 who found no difference in OS in patients with isolated 5q (including 5q syndrome) and those with 1 additional abnormality, although this may simply be explained by a substantial difference in the number of patients analyzed. On the other hand, a recent study that aimed to identify predictors of OS in 5q MDS patients13 in a large series of patients (n ¼ 506) from various MDS registries worldwide who had received only supportive care demonstrated that the OS of patients with 2 abnormalities in addition to the 5q deletion was significantly lower than that of
Figure 1 Median Time of Lenalidomide Therapy in 4 Indicated Types of MDS According to WHO Classification, 2001. Error Bars Represent Variability Outside Upper and Lower Quartiles; Dots Represent Individual Outliers
Abbreviations: MDS ¼ myelodysplastic syndromes; WHO ¼ World Health Organization.
Gregor Aschauer et al Table 4 Red Blood Cell Transfusion Independence (100%) During 2 Months After Discontinuation of Lenalidomide Therapy MDS Subtype
Evaluable Patients, n (%)
5q syndrome 5q plus other aberrations 5q isolated Other MDS Total
18 3 5 10 34
(66) (66) (80) (50) (64)
Abbreviation: MDS ¼ myelodysplastic syndrome.
patients with < 2 additional abnormalities. Moreover, recent reports suggest that the prognostic value of additional cytogenetic abnormalities is retained even in low/intermediate-1 MDS patients with del(5q) treated with lenalidomide.14,15 WHO grade 3 and 4 cytopenias were frequently observed; however, many of them were already present at baseline as part of the underlying disease of MDS. Although it is the most limiting toxicity of lenalidomide, cytopenias caused discontinuation of therapy only in 2 patients. Without active treatment, the 5-year actuarial risk of 5q MDS patients progressing to AML is 38.3% according to a recent international long-term retrospective evaluation of approximately 300 patients with primary 5q MDS and best supportive care only.13 With lenalidomide therapy, rates of progression to AML were evaluated in several studies on 5q patients (with and without additional cytogenetic abnormalities) with low to intermediate-1 risk according to IPSS. In the long-term follow-up analysis by Göhring et al,16 36% of the patients progressed to AML at a median follow-up of 3.3 years. Explicitly analyzing rates of progression to
AML in lower risk 5q MDS patients with or without lenalidomide therapy, the study by Adès et al17 reported comparable rates for the 2 study arms. These data suggest that lenalidomide therapy has apparently no effect on the rate of progression to AML in MDS/ 5q. The only lenalidomide-related phenomenon in this context is a significantly lower risk of progression to AML in patients with a cytogenetic and erythroid response than in those with disease that does not respond to therapy, making response to lenalidomide a prognostic marker for AML progression.5,15,18,19 In our study, 22.9% of all MDS patients (n ¼ 48) experienced a progression to AML. Considering the relatively short total observational period (total population, approximately 8 months), this rate appears to be higher compared to previous reports. We therefore subsequently performed a detailed analysis of each single questionnaire and related patient characteristics (as far as available) according to well-known risk factors for AML progression.9,14,19 Indeed, a large number of patients in our population had various AML risk factors: transfusion burden at study entry (76%), 1 additional abnormality (42%), nonresponse to lenalidomide therapy (37%), intermediate 2 or greater IPSS (22%), and other non-5q deletion MDS (32%). In addition, our population was very heterogeneous compared to those in the above-mentioned studies, which focused mainly on 5q patients. In our study, 32% of all patients had a non-5q phenotype. Four of them progressed to AML. Taking into consideration only patients with a 5q deletion (with or without additional aberrations) (n ¼ 34), 7 of them experienced progression to AML (Table 5). However, one of them belonged to a higher risk class according to IPSS (patient 26) and had > 5% blasts in the BM before initiation of lenalidomide therapy, another was heavily pretreated (patient 37), and a third exhibited additional aberrations (patient 25). Furthermore, a single progression to AML occurred after a rather long period of successful lenalidomide therapy (23 cycles). Hence, the higher
Table 5 Patients With Baseline AML or AML Evolution During Observational Period Patient No.
MDS Subgroup
MDS Disease Status
AML Evolution
5
5q plus other aberrations
AML
e
14
5q isolated
AML
e
5q syndrome
Low risk
After 15 cycles of LL therapy
Baseline AML
5q deletion 11
17
5q syndrome
Low risk
After 10 cycles of LL therapy
25
5q plus additional aberrations
NA
After 2 cycles of LL therapy
26
5q isolated
Int-2
After 22 cycles of LL therapy
33
5q syndrome
Low risk
After 23 cycles of LL therapy
37
5q syndrome
Low risk, highly pretreateda
NA
44
5q syndrome
Low risk
After 3 cycles of LL therapy
22
Other MDS
Int-2
After 2 cycles of LL therapy
15
Other MDS
Int-1
After 4 cycles of LL therapy
24
Other MDS
NA
After 5 cycles of LL therapy
34
Other MDS
Highly pretreatedb
After 1 cycle of LL therapy
Non-5q deletion
Abbreviations: AML ¼ acute myeloid leukemia; C-HAM ¼ continuous infusion of Ara-C and mitoxantrone; IA ¼ idarubicin and Ara-C; Int ¼ intermediate; LL ¼ lenalidomide; MDS ¼ myelodysplastic syndromes; NA ¼ not available; R-FCM ¼ rituximab plus fludarabine, cyclophosphamide and mitoxantrone. a Double induction with IA þ C-HAM. b Secondary MDS after therapy with R-FCM for mantle cell lymphoma.
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Treatment of MDS in Austria Figure 2 Overall Survival of MDS Patients After Therapy With Lenalidomide. (A) Total Population; Dotted Lines Indicate 95% Confidence Interval. (B) Types of MDS According to WHO Classification, 2001, as Indicated
Abbreviations: MDS ¼ myelodysplastic syndromes; WHO ¼ World Health Organization.
incidence of AML progression in our study seems to be a consequence of a very heterogeneous population rather than related to lenalidomide therapy. In summary, lenalidomide has frequently been administered by Austrian physicians for the treatment of MDS, particularly in patients with a good prognosis according to karyotype and IPSS and in patients who have received only few MDS-specific pretreatments. Effectiveness and tolerability were comparable to that reported in several randomized clinical trials, with the most promising results observed in patients with 5q syndrome and MDS associated with isolated del(5q). We found no evidence suggesting that lenalidomide may affect progression to AML. Meanwhile, lenalidomide was approved by the EMA for use in low or intermediate-1 risk MDS patients who have the deletion 5q chromosomal abnormality and no other chromosomal abnormalities, are dependent on RBCT, and for whom other treatment options have been found to be insufficient or inadequate.
Clinical Practice Points Lenalidomide was approved by the EMA for use in low or
intermediate-1 risk MDS patients who only have the deletion 5q chromosomal abnormality, are dependent on RBCT, and for whom other treatment options have been found to be insufficient or inadequate. The aim of the present study was to characterize the patient population already receiving lenalidomide in Austria and analyze treatment modalities, outcome, and safety of the lenalidomide therapy in this real-life situation. In the total population—which was very heterogeneous—the median rate of achieved transfusion independence was 64%. These data suggest that the effectiveness of lenalidomide in MDS patients in terms of transfusion independence is very
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similar in clinical practice compared to patients treated in clinical studies.
Acknowledgment We thank Eva Mueller for her support in document preparation, which was funded by Celgene Austria. This study was supported by an unrestricted research grant from Celgene Austria to the Department of Internal Medicine I for Medical Oncology, Hematology, and Gastroenterology at the Barmherzige Schwestern Hospital in Linz, Austria. We thank Birgit Petzer for proofreading.
Disclosure R.S. was supported by Verein Senioren-Krebshilfe. S.B. received research support from Celgene. The other authors declare that they have no conflict of interest.
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does it relate to the original lenalidomide experience in MDS? Cancer 2009; 115: 5202-9. Göhring G, Giagounidis A, Büsche G, et al. Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression. Ann Hematol 2010; 89:365-74. Adès L, Lebras F, Sebert M, et al. Treatment with Lenalidomide does not appear to increase the risk of leukemia progression in lower risk myelodysplastic syndrome with 5q deletion. A comparative analysis by the GFM. Haematologica 2012; 97:213-8. List AF, Wride K, Dewald GW, et al. Cytogenetic response to lenalidomide is associated with improved survival in patients with chromosome 5q deletion. Leuk Res 2007; 31(suppl 1):S38, abstract C028. List AF. Recent advances in the treatment of MDS. Clin Adv Hematol Oncol 2007; 5(7 suppl 10):4-14.
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