Management of MDS with Isolated Del(5q) Patients in the European MDS (EUMDS) Registry: A Report on 197 Cases

Background 'MDS with isolated del(5q) is a specific WHO 2016 subtype of MDS with characteristic morphological genomic features, and response of anemia to the immunomodulatory agents lenalidomide (LEN). LEN is approved in this indication, although Erythropoiesis Stimulating Agents (ESA) and red blood cell transfusion (RBCT) are still regarded first line options for anemia management.

We analysed the characteristics and outcome of 197 MDS with del(5q) patients in the prospective international EUMDS registry.

Methods Patients included in EUMDS registry are diagnosed and treated according to local or national recommendations. Treatment options (LEN, ESA, RBCT only) are thus in part influenced by local routines and reimbursement systems. Patient follow-up is recorded electronically every 6 months ("visit") in a central database. Standard descriptive methods and time to event analyses were used to examine differences in baseline factors by diagnosis, treatment response and overall survival (OS).

Results Of 2469 EUMDS patients, 197 (8%) met criteria for 'MDS with isolated del(5q)'. Median follow-up was 4.3 yrs (3.8 years for all EUMDS patients). 77% were female, and median age was 73y. In comparison to the 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),and were more likely to have been transfused at registration (p=0.05) as well as during follow up (p<0.001).

To date, 168/197 patients received one or more active interventions. First line treatment was RBCT in 96 patients and ESA in 55 patients. In total, 92 patients received LEN, 17 as 1^st line, 41 as 2^nd line and 34 as 3^rd line treatment. Median time on treatment was 369.5 days.

Mean baseline serum epo (sEPO) (available for 108/197 patients) was 317.8 IU/ L, compared with 148.9 IU/L for all EUMDS Registry patients. Of 92 patients who received LEN, 29 also received anti-coagulants and 24 patients received concurrent ESAs. As 26 patients were not transfused prior to starting LEN, it is difficult to make comparisons between treated and non-treated groups.

Fifty patients were transfusion dependent before LEN. Of there, 76% have responded. Response duration was longer in patients treated with LEN prior to the initiation of regular RBCT (88% vs 60%). Response rates varied depending on transfusion dose-density prior to initiation of LEN and were highest in del(5q) patients with low RBCT burden. Response duration to LEN was broadly comparable to previously published clinical trial data, namely 4.5 study intervals (maximum of 27 months) in patients without prior RBCT vs. 3 intervals (maximum of 18 months) in patients with prior RBCT. Compared with RBC transfusion dose density interval before starting LEN (mean 1.059), dose density interval decreased in the first visit after starting LEN (mean 0.867). Haemoglobin levels increased from 8.8 g/dL before LEN, to 10.3g/dL at visit after starting LEN.

No difference in OS or disease progression (to higher risk MDS or AML) was noted for patients treated with LEN vs. not ( OS - adjusted Hazard Ratio, age and sex, 95% Confidence Interval: 0.67 [95% CI:0.35-1.29], LEN 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. Response rate to LEN therapy appeared to be higher, and response duration longer in patients with no prior RBCT. More than half of transfusion dependent patients will respond to LEN.

Mandac Smoljanovic:Takeda: Honoraria; Bristol Myers Squib: Honoraria, Speakers Bureau; Bristol Myers Squib: Honoraria, Speakers Bureau. Fenaux:Jazz: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Symeonidis:WinMedica: Research Funding; Servier SOBI: Membership on an entity's Board of Directors or advisory committees; Vianex: Research Funding; Roche: Research Funding; Rafarm: Honoraria; Demo/Apopharma: Research Funding; Astellas: Research Funding; Abbvie, Amgen, Astra-Zeneca, BMS, GenesisPharma, Gilead, Glaxo, Integris, Janssen, Novartis, Pfizer, Sanofi, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sanz:Janssen Pharmaceuticals, Inc.: Other: Teaching and Speaking; Celgene Corporation: Consultancy; Novartis Oncology: Consultancy; La Hoffman Roche Ltd.: Other: Advisor or review panel participant; Helsinn: Honoraria, Other: Advisor or review panel participant; Abbvie Pharmaceuticals: Other: Advisor or review panel participant; Takeda Pharmaceuticals Ltd: Other: Advisor or review panel participant; takeda: Honoraria. Stauder:BMS: Honoraria. Germing:Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Madry:Abbvie: Membership on an entity's Board of Directors or advisory committees; Teva: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees. van Marrewijk:Novartis: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding; EUMDS Registry: Current Employment, Other: Project Manager; B.V. Oncology Europe: Research Funding; MDS-RIGHT: Research Funding. de Witte:Gilead: Consultancy; Novartis: Consultancy; Amgen: Research Funding.