Lenalidomide Is Active in Relapsed and Refractory NHL

January 1, 2007

Treatment with the thalidomide-like immune modulator lenalidomide (Revlimid) led to a 41% response rate in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL)

ORLANDO—Treatment with the thalidomide-like immune modulator lenalidomide (Revlimid) led to a 41% response rate in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), according to a report at the 48th Annual Meeting of the American Society of Hematology (abstract 531). The total clinical response rate approached 60% when patients with prolonged stable disease were combined with those who had a major objective response. Lenalidomide was well tolerated, with grade 3-4 adverse events uncommon.

"Lenalidomide demonstrated activity in every aggressive histology treated," said Peter Wiernik, MD, director of the Comprehensive Cancer Center at Our Lady of Mercy Medical Center, Bronx, NY. Reviewing the background of the clinical study, Dr. Wiernik said lenalidomide has a more potent immunomodulatory activity than does thalidomide and has a more favorable side-effect profile, including little or no neuropathy or sedation and a lower incidence of constipation.

Lenalidomide is FDA approved for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with the 5q deletion. In addition, the agent has been reported to be active in chronic lymphocytic leukemia and cutaneous T-cell lymphoma.

Dr. Wiernik presented data from a phase II, single-arm, open-label clinical study involving 40 patients with relapsed or refractory aggressive NHL. The patients had received at least two prior forms of treatment and all had measurable disease of at least 2 cm. Treatment consisted of oral lenalidomide 25 mg/d on days 1 to 21 of a 28-day cycle. Therapy continued for 52 weeks or until progression or development of intolerable side effects.

Of 32 patients evaluable for response, 15 had diffuse large B-cell lymphoma (DLBCL), 12 had mantle cell lymphoma, 3 had follicular lymphoma, and 2 had transformed lymphoma. The median age was 66 years; patients had received a median of three prior regimens. Three-fourths had stage III-IV disease.

Four Complete Responses

Lenalidomide therapy led to four complete responses and nine partial responses for a response rate of 41%. Six patients had stable disease for at least 4 months, for a total clinical response rate of 59%. Major objective responses occurred in four patients (27%) with DLBCL, six (50%) with mantle-cell lymphoma, two (67%) with follicular lymphoma, and one (50%) with transformed lymphoma.

Dr. Wiernik noted, "Lenalidomide also was active in patients who had prior autologous stem cell transplantation.

Although it's still early, the progression-free survival is encouraging." Among the six patients who had undergone autologous stem-cell transplants, lenalidomide led to a complete response in one and a partial response in four (83% overall).

Grade 4 adverse events were "rather strikingly absent," Dr. Wiernik observed. Four patients had thrombocytopenia, three had neutropenia, and one each had myocardial infarction, febrile neutropenia, pulmonary embolism, intermittent rash, and anemia. Grade 3 adverse events consisted of neutropenia in nine patients, thrombocytopenia in five, leukopenia in four, and fatigue in two.

"Further investigation of lenalidomide in NHL as monotherapy and in combination with other agents is warranted," Dr. Wiernik said. "The same dose and schedule used in this study will be studied in a phase II North American study involving an estimated 128 patients."