Durable Erythroid and Cytogenetic Response After Short-Term Lenalidomide Treatment In Two Patients with Myelodisplasia and Del(5q)
Authors: Capodanno Isabella , Avanzini Paolo , Franchi Fabrizia , Merli Francesco 
Published: October 2019

Abstract
Abstract 4977

Introduction
Lenalidomide (Len) is an immunomodulatory drug that has a selective inhibitory effect on the del(5q) clone. The exact mechanism of action has not been defined: Len is known to have multiple biologic activities and an impressive effect on myelodysplasia (MDS) with deletion of the long arm of chromosome 5, leading to transfusion-independence, a complete erythroid and cytogenetic response in over 65% of cases.
Similar responses were also seen in patients with MDS and a complex karyotype including del(5q), which usually have a poor prognosis.
Lenalidomide leads to an important myelotoxicity in 50% of patients, so the optimal schedule merits discussion.
In this report we describe unexpected erythroid and cytogenetic responses in two elderly patients with del(5q) MDS treated with Len for less than 12 wks.

Case Reports
Since November 2008 we have been treating two female patients with a diagnosis of MDS and a deletion of the long arm of chromosome 5 [del(5q)] with Len. Both patients had a low-int-1 IPSS risk.
At the time of diagnosis severe cardio-pulmonary co-pathologies were present, therefore we observed a very bad tolerance to anaemia.
The monthly transfusion requirement before starting treatment was 6 packed RBC units.
Len was started at a full dose (10 mg/d for 21 days every 4 wks).
Patient 1 received a diagnosis of “5q- syndrome” (Fig. 1). She stopped therapy after only 10 days due to severe agitation and panic attacks; however, one month later we observed a progressive reduction of transfusion need. Two months later, the patient was transfusion-free and the response had been ongoing for 6 months; she obtained a very good partial cytogenetic response. After 6 months the anaemia worsened again; we started Len 10 mg/d, but after 15 days the therapy was stopped due to the same side effects. Forty days later, we observed transfusion-independence for another 6 months, and a very good partial cytogenetic response.
When the patient's condition worsened again, she was treated with Len 10 mg on alternative days with a better tolerance. After the first cycle, she presented the same side effects. Again the karyotype analysis showed a very good partial cytogenetic response.
In Patient 2 the morphologic analysis was compatible with RAEB-1 and the cytogenetic analysis showed a [del(16)(q22)] together with del (5q) (Fig. 2). Len was stopped after 15 days due to renal impairment, cardiopulmonary and cardiac failure; she was then given only palliative therapy, but four wks later she achieved a complete erythroid response and remained transfusion-free for one year. In January 2010 the patient worsened and started Len again (10 mg/d for 21 dd every 4 wks) with good tolerance, a complete hematologic response and a very good partial cytogenetic response.
Hematologic responses are illustrated in Tab. 1 and Tab. 2.
In these two patients, after a very short treatment with Len we observed a complete erythroid response and a very good partial cytogenetic response. The median time to achieve the response was 6 wks (range 4–8 weeks).
Transfusion-independence was durable (24 and 38 weeks respectively).

Discussion
Giagounidis et al (Ann. Hematol, 2007) describe two similar cases in which short-time Len treatment was given and a good response was obtained.
One of our patients experienced grade III hematologic toxicity during the first cycle of therapy; despite this, we did not observe severe infectious or hemorrhagic complications.
Despite the very short duration of Len treatment in our two patients, in both cases we achieved a very good partial cytogenetic response.
Conclusions
We observed unexpected effects of Len in myelodysplastic patients with del(5q) and a low-int1 IPSS risk who were treated for a very short period; additionally, this response was observed again at least twice when treatment was begun again: although these patients obviously represent only selected cases, the good erythroid and cytogenetic responses suggest that some patients with MDS and del(5q) may benefit from Len treatment even if this must be discontinued.

Disclosures:
No relevant conflicts of interest to declare.