Phase 2 Clinical Trial of Oral Lenalidomide, Cyclophosphamide, and Prednisone (RCP) for Newly Diagnosed Multiple Myeloma Patients.

Effective and convenient regimen is appealing for Multiple Myeloma (MM) therapy. Lenalidomide and dexamethasone combination is highly effective in MM. However, at the FDA approved dose, dexamethasone related toxicity remains problematic. We previously reported that oral cyclophosphamide and prednisone, when combined with thalidomide, was active and well tolerated in relapsed MM (Oncologist Jan, 2007). Using the similar approach, we now explore the efficacy of all oral, dexamethasone-sparing combination of lenalidomide, cyclophosphamide and prednisone in newly diagnosed MM.

The treatment protocol consisted of lenalidomide given orally at a dose of 25 mg daily on days 1–21 of a 28-day cycle, cyclophosphamide at a dose of 50 mg b.i.d. days 1–21 of a 28-day cycle, and prednisone 50 mg q.o.d. Patients also received an aspirin once daily as thromboprophylaxis. Response was defined as a decrease in serum monoclonal (M) protein by 50% or higher and a decrease in urine M protein by at least 90% or to a level less than 200 mg/24 hours. Responses were assessed on intent to treat basis.

Twenty-one patients were enrolled from October 2007 to July 2009. The median age was 67 years (range, 41-76). 7 patients (33%) had ISS stage II and 3 (14%) had stage III disease. The median number of cycles was 6 (range: 1 – 6). The response is not evaluable in 4 patients who are still undergoing the first cycle of therapy.

Among the remaining 17 patients, the over all response rate was 94%. The best response based on intent to treat basis was 83%, including CR: 1 (6%), nCR: 1 (6%), VGPR: 3 (18%), PR: 11 (65%) and less than PR: 1 (6%). Overall, 14 of the 21 enrolled patients have discontinued study treatment. Reasons for treatment discontinuation are: completed study per protocol (10), disease progression (1), and adverse event (1) and alternate treatment (1).

Hematologic toxicities were the most common with grade 3 neutropenia seen in 10 patients. Infections were seen in 10 patients (5, febrile neutropenia and 5, with normal ANC). Non hematologic toxicities were fatigue, gastrointestinal side effects, neuropathy and mood swings. Specifically, neuropathy was reported in 5 patients. All were grade I. Five patients had grade 4 metabolic abnormalities (2 renal failure attributed to dehydration and tumor lysis, 2 hyperglycemia. and 1 hypokalemia). Five patients had dose adjustments, most commonly due to hematological toxicity attributed to lenalidomide or cyclophosphamide. Seven patients had stem cell collection. In all, sufficient numbers of stem cells were collected for the transplantation use. To date, five have undergone high dose chemotherapy and stem cell transplantation. Three patients with PR on RCP achieved VGPR. Response is not yet evaluable in the 2 remaining patients.

The combination of lenalidomide, cyclophosphamide, and prednisone (RCP) has excellent activity in the setting of newly diagnosed myeloma. Overall toxicities were manageable. Myelosuppression was a significant toxicity and attenuated with dose reductions. The study is still ongoing with the total accrual goal of up to 48 patients. The updated data for response and toxicities will be presented at the ASH Annual Meeting.

Abonour:Celgene: Honoraria; Millennium: Honoraria.