CLINICAL NEWS
recent clinical experience suggested that the response rate to lenalidomide
could be increased by the addition of ESA [in patients without del5q].”
To establish the benefit of adding erythropoietin to lenalidomide, Dr.
Toma and colleagues conducted a randomized, intent-to-treat, phase III study
of 131 patients with lower-risk, non-del5q, RBC transfusion-dependent MDS
refractory to ESAs. Eighty-one patients (61.8%) had primary resistance to
ESAs, and 50 patients (38.1%) relapsed after an erythroid response.
All patients in the study were classified as either “low-risk” (43.5%) or
“intermediate-1” (56.5%), according to the International Prognostic Scoring System (IPSS), and required a median of six red blood cell units every
eight weeks.
Patients were randomized to receive either:
• Lenalidomide alone (10 mg per day for 21 days for 4 weeks; n=65)
• Lenalidomide (10 mg per day for 21 days for 4 weeks) plus
erythropoietin beta (60,000 units per week; n=66)
Thirty-two patients (16 in each study arm) did not receive the full four
planned courses, due to adverse events (21 patients), early death (4), investigator’s or patient’s decision (5), suicide (1), and loss to follow-up (1).
In the intention-to-treat analysis, erythroid response after four treatment cycles (the study’s primary endpoint, defined as reduction of >4
units of RBC transfusion) was observed in 41 patients: 15 (23.1%) in the
lenalidomide arm and 26 (39.4%) in the lenalidomide–erythropoietin
arm (p=0.044). Median time to erythroid response was four months in
both arms.
Median response duration was higher in the lenalidomide group
compared with the lenalidomide–erythropoietin group, though the finding
was not significant (18.1 months vs. 15.1 months; p=0.64). Seven of the 15
responders in the lenalidomide arm eventually relapsed, as did 13 of the 26
responders in the combination arm.
There was, however, no significant increase in RBC transfusion-independence rate with the combination arm (13.8% in the lenalidomide arm
and 24.2% in the lenalidomide–erythropoietin arm; p=0.13), “possibly due
to the insufficient size of our patient population or to the high transfusion
burden in our patients,” the investigators noted. Transfusion-independence
rates were significantly different, though, when the analysis was restricted
to patients who did not receive more than four RBC units in the eight
weeks before study inclusion.
Among the 58 non-responders, two patients (one in each study arm)
experienced a late response – four weeks after treatment was discontinued
in the lenalidomide arm and six weeks in the lenalidomide–erythropoietin
arm.
After analyzing patient characteristics to identify factors that predicted
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