Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma.
OBJECTIVE
Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).


METHODS
Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety.


RESULTS
Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).


CONCLUSIONS
Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.
Witzig
Thomas E
TE
Mayo Clinic, Rochester, MN 55905, USA. witzig@mayo.edu
Wiernik
Peter H
PH
Moore
Timothy
T
Reeder
Craig
C
Cole
Craig
C
Justice
Glen
G
Kaplan
Henry
H
Voralia
Michael
M
Pietronigro
Dennis
D
Takeshita
Kenichi
K
Ervin-Haynes
Annette
A
Zeldis
Jerome B
JB
Vose
Julie M
JM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide