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

An 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 challenging. We report the efficacy and side effect profile of an all oral, dexamethasone-sparing combination of lenalidomide, cyclophosphamide and prednisone in newly diagnosed MM.

The treatment protocol consisted of lenalidomide (Revlimid®) 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 (RCP). Responses were assessed on intent-to-treat basis based on the International Uniform Response Criteria. Treatment was planned for 6 cycles. Responding patients proceeded to observation, or transplantation, based on patient's preferred choices. All patients received, unless contraindicated, aspirin prophylaxis (81 or 325 mg daily) for prevention of deep-vein thrombosis, acyclovir for herpes zoster prevention, and bisphosphonates.

Forty six patients were enrolled from October 2007 to August 2010. Median follow up duration was 5.6 months. At this time, 38 of 46 patients are evaluable for confirmed responses (i.e., off-study or completed at least 4 cycles of therapy). The median age was 63 years (range, 41–76). 16 patients had ISS stage II (42%) and 8 (21%) had stage III disease. The median number of cycles was 6 (range: 1 – 6). Among the 38 evaluable patients, the overall response rate was 95%, consisting of CR: 1 (3%), VGPR: 9 (24%) and PR: 26 (68%). One patient had stable disease (1%) after the first cycle and treatment is ongoing. One patient had progression (3%). Thirty twoof 38 patients have discontinued study treatment. Reasons for treatment discontinuation are: completed study per protocol (24), disease progression (3), adverse event (2), non compliance (1), alternate treatment (1) and withdrawal of consent unrelated to toxicity (1).

The most common toxicity was sensory neuropathy (24%): 8 (21%) grade I and 1 (3%) grade II. Other common toxicity included constipation (21%), pruritus (21%) and edema of limbs (18%). The most common hematologic toxicity was neutropenia (18%); 4 grade III and 2 grade IV. Infections were seen in 4 patients (2 febrile neutropenia and 2 with normal ANC). Five patients had grade 4 metabolic abnormalities (2 renal failure attributed to dehydration and tumor lysis, 2 hyperglycemia. and 1 hypokalemia). Thirteen patients had dose adjustments or interruption, most commonly due to hematological toxicity attributed to lenalidomide or cyclophosphamide. Twenty-five patients had stem cell collection. In all, sufficient numbers of stem cells (CD34+ cells ≥ 4.0 × 10⁶ cells/kg) were collected for the transplantation use. To date, fifteen have undergone high dose chemotherapy and stem cell transplantation. Of eight patients with PR on RCP, seven achieved VGPR and one achieved CR post transplant. Of four patients with VGPR on RCP, 2 achieved CR and 2 remained in VGPR post transplant. Post-transplant response is not yet evaluable in the 3 remaining patients.

The combination of lenalidomide, cyclophosphamide, and prednisone (RCP) has excellent activity in the setting of newly diagnosed myeloma. Overall toxicities were manageable. 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.

No relevant conflicts of interest to declare.