Abstracts from the EHA Conference

[Birgitta-A]

Hi All,
Now the abstracts from the European Hematology Conference 2013 in Stockholm are available.
https://b-com.mci-group.com/EventProgramme/EHA18.aspx
Kind regards
Birgitta-A

[Neil Cuadra]

One abstract in particular caught my eye:

EHA18ABSSUB-3848

MULTICENTER STUDY EVALUATING THE IMPACT OF HYPOMETHYLATING AGENTS AS BRIDGING THERAPY TO HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MYELODYSPLASTIC SYNDROMES

The authors studied the effects of azacitidine or decitabine before a transplant, to learn whether these drugs had a positive or negative effect on the subsequent transplant. They found that taking these hypomethylating agents can make engraftment take longer, which is a disadvantage. However, they also found that patients with higher blast counts had longer "event-free" survival if they took hypomethylating agents before their transplant, despite the longer time to engraftment.

As is common, the authors recommend more research, but this lends weight to the notion that it is suitable for high-risk MDS patients to take Vidaza or Dacogen even if they are going to have a transplant, and that this is less desirable for low-risk MDS patients.

[Birgitta-A]

Hi All,
Here is an abstract about Revlimid (lenalidomide) combined with EPO.

EHA 2013 A RANDOMISED STUDY OF LENALIDOMIDE (LEN) +/- EPO IN RBC TRANSFUSION DEPENDENT (TD) IPSS LOW AND INT-1 (LOWER RISK) MYELODYSPLASTIC SYNDROMES (MDS) WITHOUT DEL 5Q RESISTANT TO EPO
Andrea Toma 1,*, Sylvie Chevret 2, Olivier Kosmider 3 et al. 1Hopital Henri Mondor, Creteil, 2Hopital Saint Louis, 3Hopital Cochin, Paris, France.

Background
ESAs, the first line treatments of anemia in non del 5q lower risk MDS, yield only 40-50% responses. LEN gives RBC transfusion independence (TI) in about 25% of ESA resistant (or relapsing) TD lower risk MDS without del 5q (Raza, Blood, 2008), and a gene expression signature can predict response (Ebert, Plos Med 2008).

Aims
We randomized in this patient population LEN alone and LEN+EPO.

Methods
In this prospective multicenter open-label phase II study, lower risk MDS patients without del 5q, with TD (≥4 RBC units during the previous 8 weeks (w)) and with ESA resistance or relapse after a response were randomized between LEN alone, 10mg/d x 21 d/4 w (L arm) or LEN (same schedule) + EPO beta, 60 000 U/w (LE arm). The primary endpoint was erythroid response (HI-E, IWG 2006 criteria) after 4 treatment cycles. Secondary objectives included identification of biomarkers of response.

Results
Between July 2010 and June 2012, 132 patients (pts, 66 / arm), median age 73 (range 46-88), M/F: 88/44 were enrolled. Median TD was 6 RBC units/8w (range 2-18). IPSS was Low in 45% and Int-1 in 55% pts. Pretreatment characteristics did not differ between the 2 groups.

All but 3 pts, who withdrew consent (2L+1LE), were evaluable for response. In this ITT population, HI-E was obtained in 15 pts (23.4%) in L arm and 26 (40.0%) in LE arm (RR= 1.7, p= 0.043, chi2 test), and TI in 9 (14.1%) versus 16 (24.6%) pts (RR=1.7, p= 0.13).

In the 99 pts who completed 4 treatment cycles, 41 achieved HI-E, including 15/49 (30.6%) in L arm versus 26/50 (52.0%) in LE arm (p= 0.03), and TI in 9 (18.4%) versus 16 (32.0%) pts (RR= 1.7, p=0.12). Side effects (cytopenias and 1 DVT/arm) were similar in the 2 arms.

A 29-gene expression profile signature predicting HI-E to L or LE, different from that previously published, was identified and a polymorphism in the CRBN gene (Kosmider, submitted) was significantly associated with HI-E in the entire cohort (p=0.034).

Summary / Conclusion
LEN + EPO yielded a significantly better erythroid response than LEN alone in lower risk MDS patients with anemia resistant to ESA alone. A gene expression signature and a CRBN gene polymorphism correlated with the erythroid response.

Kind regards
Birgitta-A