Lenalidomide Demonstrates Effectiveness in Aggressive B-Cell NHL

New Orleans, LA — Lenalidomide (Revlimid) has promising anti-tumor activity in aggressive B-cell non-Hodgkin lymphoma (NHL), with a predictable toxicity profile. Results of an international phase II study suggest that lenalidomide should be studied in combination with other regimens in the treatment of the various subtypes of aggressive NHL, including diffuse large B-cell lymphoma (DLBCL), transformed lymphoma, follicular grade III lymphoma, and mantle cell lymphoma (MCL), according to Thomas E. Witzig, MD, Mayo Clinic College of Medicine, Rochester, MN, who presented results of this study at the 51^st ASH Annual Meeting. Patients with aggressive B-cell lymphomas can be effectively treated, but they may fail to respond to initial therapy or relapse. Few effective treatment options are available for these patients, Dr Witzig noted.

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Lenalidomide is approved by FDA for the treatment of myelodysplastic syndromes and as part of a treatment regimen for multiple myeloma. Preliminary studies suggested that lenalidomide has good activity in NHL. The large, international, phase II trial was undertaken to confirm the safety and efficacy of single-agent lenalidomide in patients with relapsed or refractory aggressive B-cell lymphoma after at least 1 prior therapy. Patients were required to have at least one measurable lesion 2 cm. Patients were treated with 25 mg of oral lenalidomide daily on days 1 through 21 of a 28-day cycle. Therapy was continued until disease progression or unacceptable toxicity.

The study included 217 patients with a median age of 66 years (range, 21-87 y). NHL subtypes included DLBCL (n = 108), MCL (n = 57), follicular grade III lymphoma (n = 19), and transformed lymphoma (n = 33). A total of 97 patients (45%) had intermediate or high International Prognostic Index scores, and median time from diagnosis was 2.7 years. Patients had undergone a median of 3 prior treatments, with 205 (94%) receiving rituximab (Rituxan).

Overall response rate (ORR) was 35%, which encompassed a complete response/unconfirmed complete response (CR/CRu) rate of 13% and a partial response rate of 22%. Stable disease was observed in 21% of patients. Median progression-free survival (PFS) was 3.7 months, and median duration of response was 10.6 months. Responses were observed in all histological subtypes and irrespective of prior therapies, Dr Witzig said.

Response to Lenalidomide by Histological Subtype

Subtype

ORR, %

Median PFS, mo

Median DR, mo

All (n = 217)*

35

3.7

10.6

DLBCL (n = 108)

28

2.3

4.5

MCL (n = 57)

42

5.7

Not reached

FL-III (n = 19)

42

6.3

Not reached

TL

45

4.6

12.5

DLBCL indicates diffuse large B-cell lymphoma; DR, duration of response; FL-III,

follicular grade III lymphoma; MCL, mantle cell lymphoma, ORR, overall response rate;

PFS, progression-free survival; TL, transformed lymphoma.

*Updated data from meeting presentation.

In the 73 patients who underwent stem cell transplantation previously, ORR was 37%. ORR was 29% in patients refractory to their last therapy and 33% in those refractory to rituximab (n=117), defined as response lasting <6 months or no response. Median duration of response was 10.6 months. For patients who achieved CR/CRu, median duration of response had not been reached at a median follow-up of 9.2 months.

The tolerability profile of lenalidomide was consistent with other studies of lenalidomide in hematologic malignancies. Reversible myelosuppression was the most common adverse effect. The rates of grade 2-3 adverse events were 41% for neutropenia, 19% for thrombocytopenia, and 9% for anemia. Dose adjustments due to adverse events were required for 44% of patients, and 22% discontinued treatment because of adverse events. Trials are currently underway to assess the role of lenalidomide in the treatment of aggressive NHL as a single agent, as part of combination chemotherapy, and in the maintenance setting. ASH Abstract 1676.

Authors received funding from Celgene.

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