Results of a Phase II Study of Lenalidomide in Combination with Rituximab for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL)

Indolent non follicular B-Cell Lymphomas (INFL) are an eterogenous group of lymphomas and include small lymphocityic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL). Relapsed INFLs in advanced stage have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Lenalidomide (R^®) is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R^® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL.

Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R^® 20 mg once daily on days 1–21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R^® when given in combination with R and to assess the safety of R2 evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were progression free survival (PFS), event free survival (EFS) and duration of remission (DR).

From July 2010 and June 2012, 39 patients were enrolled: 19 had SLL, 11 had LPL, 4 splenic MZL, 3 extranodal MZL and a 2 nodal MZL. Median age was 68 years (51–76) and 58% were male. LDH value was increased in 17% of pts and β-2-microglobulin in 87%; 41% of pts had Hb<12 g/dL and 62% were bone marrow positive. At time of current analysis treatment and response data were available in 27 pts. Overall treatment was completed in 18 pts (67%); in 9 cases treatment was interrupted prematurely primarily due to hematological toxicity (n=5) and due to disease progression (n=4). Of the 27 pts, 5 achieved a complete remission and 9 a partial remission with an ORR of 52%. In general, the regimen R2 was relatively well-tolerated. Grade 3–4 hematological events included neutropenia occurring in 50% of pts, infection in 7% and piastrinopenia in 3%. Growth factors were administered in 60% of pts. The median dose intensity was 0.94 for R and 0.92 for R^®. With a median follow-up of 13 months (range 1–36), overall 9 pts had a lymphoma progression and 2 of them died. The 1-year overall survival and the 1-year PFS were 92% (IC95% 57–99%) and 78 months (IC95% 54–91%) respectively.

In our trial follicular histology was an exclusion criteria and all pts were relapsed/refractory to immuno-chemotherapy rituximab-containing regimens. Thus the results observed with the chemo-free R2 scheme compare favorably with other previously reported results observed in relapsed indolent lymphoma treated with standard immuno-chenotherapy. Further the R2 combination was relatively well tolerated. In conclusion our results, although obtained in a small series of patient are encouraging and support further evaluation of R2 scheme in a larger cohort of patients.

No relevant conflicts of interest to declare.