Ricer (Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid) Is Well-Tolerated Salvage Regimen in First Relapse/Primary Refractory DLBCL Allowing Consolidation with Autologous Stem Cell Transplant

Relapsed/refractory DLBCL has poor prognosis in the rituximab era. Pts who failed Rituximab-containing initial chemo regimen within 12 mo do particularly poorly. (ORR 46–51% vs. 83–88%, EFS 20% vs. 45% at three years). Novel salvage therapies to overcome chemo resistance and maintain remission in post transplant setting are needed.

The immunomodulatory agent lenalidomide has demonstrated direct tumoricidal and antiproliferative effects in lymphoma and clinical activity and safety in multiple phase II studies in aggressive NHL.

We are conducting a phase I/II trial combining lenalidomide with RICE (rituximab, ifosfamide, carboplatin and etoposide) (RICER) as a salvage regimen in first relapse or primary refractory DLBCL. Four dose levels of lenalidomide are being evaluated in Phase I part of the study: 10mg, 15mg, 20mg, and 25mg given for 7 days (days 1–7) together with RICE. After three cycles of RICER patients with chemo sensitive disease proceed to stem cell collection (off 3^rdRICE) and consolidation with BEAM followed by autologous SCT (ASCT). Patients who recover from ASCT toxicities within 90 days are started on maintenance with lenalidomide 25mg daily for 21 days every 28 days for 12 months.

13 patients have been enrolled. DLT was not seen at 25 mg (last dose level tested) of lenalidomide during the salvage part of RICER. No unexpected toxicities were observed by adding lenalidomide to RICE. Grade 3 and 4 hematologic toxicities were comparable to RICE alone and resolved appropriately and planned dose density and dose intensity of RICER were preserved. One episode of febrile neutropenia occurred during RICER administration. No new DVT's occurred during lenalidomide administration either in salvage or in post ASCT maintenance part of the trial. Stem cell collection was successful in all but one patient. So far seven patients have completed ASCT and five patients were able to start on maintenance lenalidomide post transplantation. No unusual toxicities were observed in the peritransplantation period and there was no delay in engraftment: median days to ANC of >500 is 11, and to plts over 20K/mL is 11. In the maintenance post ASCT there was no infection but routine dose reductions were required because of myelotoxicity.

1. Adding lenalidomide to RICE (RICER) is feasible salvage regimen with no increased toxicity.

2. PET-CR rate is promising in this very refractory DLBCL population.

3. While it is premature for any definitive conclusions regarding feasibility of maintenance lenalidomide in post transplant setting, trial is ongoing with expansion in additional institutions.

Feldman:allos: Speakers Bureau; merck: Speakers Bureau; celgene: Speakers Bureau; seattle genetics: Speakers Bureau. Off Label Use: Lenalidomide in combination with chemotherapy as salvage regimen for DLBCL. Mato:Celgene: Speakers Bureau; seattle genetics: Speakers Bureau; genentech: Speakers Bureau; millennium: Speakers Bureau. Goldberg:Eisai: Speakers Bureau. Vesole:Celgene Corp.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Siegel:Celgene: Advisory Board Other, Honoraria, Speakers Bureau; Millennium Pharma: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Onyx: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Merck: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau. Goy:Milennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; J & J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.