'MDS with isolated del(5q)' is a subtype of Myelodysplastic Syndrome (MDS) with characteristic morphological and genomic features. Clinically, MDS with isolated del(5q) is uniquely responsive to immunomodulatory agents, with lenalidomide (LEN) approved for treating anemia in this indication. Erythropoiesis Stimulating Agents (ESA) and red cell transfusion (RBCT) are other options for anemia management.

The EUMDS Registry is an international prospective registry of newly diagnosed patients (within 100 days of diagnosis) with IPSS Low/Int-1-risk MDS (plus higher-risk MDS from 2017) recruiting since 1 st April 2008, currently at 146 sites in 17 countries. We describe the largest prospective Registry series of 'MDS with del(5q)' patients, with data from diagnosis.

Methods

Comparative analyses of baseline characteristics for categorical variables compared different groups by chi 2 test, and for continuous variables by Kruskal-Wallis test. p values are given with Bonferonni correction applied.

Results

Baseline characteristics

Of 2469 EUMDS patients, 197 (8%) met the WHO 2016 classification criteria for 'MDS with isolated del5q'. Median follow up is 4.3 yrs. 77% were female (34% for all EUMDS patients), and median age was 73y. In comparison to EUMDS patients lacking del(5q), patients with MDS with isolated del(5q) were lower risk at diagnosis (IPSS and IPSS-R, p<0.001), had lower Hb and higher platelet count (both p<0.001). They were also more likely to have been transfused at registration (p=0.05) and transfused during follow up (p<0.001). Mean baseline serum erythropoietin level (sEPO) (available for 108/197 patients) was 318 IU/L with 83% <500 IU/L and 33% < 100 IU/L.

Interventional management

To date, 168/197 patients received active intervention and the following sequence of interventions was observed, in order of frequency of initial intervention, RBCT>ESA>LEN:

RBCT (n=96),

- then ESA (42) then LEN (21)

- then LEN (32) then ESA (5)

ESA (n=55),

- then RBCT (30) then LEN (13)

- then LEN (9) then RBCT (6)

LEN (n=17),

- then ESA (3) then RBCT (2)

- then RBCT (2) then ESA (2)

Ninety-two patients have received LEN. In comparison with those not (yet) treated with LEN, LEN treated patients were younger (mean 70y vs 75y, p<0.013), and more likely to have ever received RBCT (83% vs 57% p<0.001) but had similar MDS-specific comorbidity index and Karnofsky Performance Status. The Table shows LEN treatment status by visit. Forty-three patients received LEN after ESA therapy. Given that baseline sEPO was not available for 46% patients, we could not evaluate compliance with ELN guideline recommendations in those patients who received LEN without a trial of ESA.

Adverse events were considered but proved too difficult to evaluate from the Registry data. For example, anticoagulant treatment data was collected, but not the specific indication.

Outcome

No difference in outcome (OS or PFS) was noted for patients treated with LEN vs. not (Figure, OS - adjusted Hazard Ratio, age and sex, 95% Confidence Interval: 0.67 [95% CI:0.35-1.29], lenalidomide treatment as a time-dependent variable).

Conclusion

EUMDS is uniquely placed to describe 'real-world' management of patients with 'MDS with isolated del(5q)' from diagnosis. To date, the largest (retrospective) case series reported had a median age 5 years younger than EUMDS, most likely representing referral bias(1). EUMDS demonstrates that most patients with MDS with isolated del(5q) require interventional therapy, and that more than half of transfusion dependent patients have received LEN. Further analysis of interventions and response will be presented.

1. Germing U, Lauseker M, Hildebrandt B, Symeonidis A, Cermak J, Fenaux P, et al. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study. Leukemia 2012;26(6):1286-92.

Figure 1
Figure 1.
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Disclosures

Fenaux: Takeda: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Symeonidis: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Demo: Research Funding; WinMedica: Research Funding; Astellas: Consultancy, Research Funding; Sanofi/Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kotsianidis: Novartis Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Bristol Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Janssen Hellas: Consultancy, Other: NONE, Speakers Bureau; Genesis: Consultancy, Other: NONE; Astellas: Other: NONE, Research Funding, Speakers Bureau. Mittelman: Janssen · Roche · Novartis · Takeda · Medison / Amgen · Neopharm / Celgene / BMS · Abbvie · Gilead: Research Funding; Novartis · Takeda · Fibrogen · Celgene / BMS · Onconova · Geron: Other: Clini; Onconova · Novartis · Takeda · Silence: Membership on an entity's Board of Directors or advisory committees; MDS HUB: Consultancy; Celgene / BMS · Novartis: Speakers Bureau. Sanz: Helsinn Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Speakers Bureau; Gilead Sciences: Other: Travel, accommodations, and expenses; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Research Funding. Stauder: Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Germing: Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Jazz Pharmaceuticals: Honoraria. van Marrewijk: EUMDS Registry: Current Employment; Novartis: Other: Educational Grants; BV Oncology Europe: Other: Educational Grants; Amgen Limited: Other: Educational Grants; Celgene International: Other: educational grants; Janssen Pharmaceuticals: Other: educational grants; Takeda Pharmaceuticals: Other: educational grants; MDS-RIGHT: Other: project budgets. de Witte: Amgen: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Janssen: Research Funding.

© 2021 by The American Society of Hematology
2021
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