Potential Synergic Effect of Lenalidomide-Rituximab Combination: Durable Complete Remissions in Refractory Diffuse Large B Cell Lymphoma

Abstract 4989

Data emerging from initial clinical trials demonstrated that Lenalidomide has a significant activity against different subtypes of aggressive B-cell lymphoma. Clinical responses are histologic subtype-dependent and most prominent in mantle cell lymphoma. The results in DLBCL were less encouraging with ORR of 26%, CR of 9%, PFS of 2.7 mo. Concurrently targeting the tumor cell itself with monoclonal antibody and targeting the immune response and microenvironment with Lenalidomide may be a promising therapeutic strategy. By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with rituximab resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma. Recently the combination Lenalidomide-Rituximab (LR) was shown to be highly efficacious in follicular NHL. Encouraging by our initial results of LR combination in patient with refractory (R/R) DLBCL (Leuk Lymphoma 2010), Institutional Multidisciplinary Meeting proposed this combination for other 8 patients with R/R DLBCL. All patients were refractory to three or more previous lines of conventional immuno-chemotherapy. All except 3 primary-refractory pts were previously autografted.

Patients received combination of Rituximab 375 mg/m2, day 1 or day 7; Lenalidomide (Revlimid), 15 mg/d for the first pt and 25 mg/d for other 8 pts, for 21 days. Dexamethasone 40mg, day 1–4 was given for first 6 pts. Initial decision on adding Dexamethasone was based on the extrapolation from the recommended regimen used in multiple myeloma, but it was abandoned in last 3 pts.

Of 9 pts enrolled on study, 8 received > 2 cycles of LR and all of them were evaluable for response. Median age for evaluable pts was 52 (range: 19–73), 3 pts are female. Of 8 evaluable pts, 5 (63%) responded to LR, including 3 pts (38%) with CR and 2 (25%) patients with PR. These two PR pts were primary refractory to chemotherapy before LR and both were grafted (1 auto and 1 allo) after three courses of LR. One pt with clinical and PET-FDG scan improvement after 3 courses of LR was included into “auto-allo” tandem program and actually in CR after PBSCT. Two pts progressed on LR treatment and were switched to palliative regimens. As regards the follow-up, 3 pts in CR are evaluable for evaluation. Two pts received 6 and one pt 8 courses of RL treatment. One patient relapsed after 24 mo of CR and other 2 patients are in CR at +11 and +6 months.

In relapsed/refractory DLBCL modest initial results of lenalidomide monotherapy emerge the use of new effective combinations. Recently several phase II studies of LR efficacy in indolent NHL were proposed. For instance, there is no published data of long-term safety and efficacy of this combination in DLBCL. Given the poor prognosis of refractory DLBCL, enrolment in already running prospective clinical trials with lenalidomide are underway and the investigation of the combination of Lenalidomide and Rituximab is further warranted.