ORLANDO, Fla.—Initial analysis of the first evaluable patients with newly diagnosed multiple myeloma enrolled in a phase 2 study has found the combination of lenalidomide, cyclophosphamide, and prednisone (RCP) to have “excellent” activity, with manageable overall toxicities.

While the combination of lenalidomide and dexamethasone is highly effective in multiple myeloma, dexamethasone toxicity at the FDA-approved dose remains a challenge. This study was initiated to determine efficacy and safety of an all oral, dexamethasone-sparing combination of lenalidomide, cyclophosphamide, and prednisone in patients with newly diagnosed multiple myeloma, Attaya Suvannasankha, of Indiana University School of Medicine and Richard L. RoudeBush VA Medical Center, Indianapolis, Ind., and colleagues reported.

In the study, patients were administered lenalidomide 25 mg/day (days 1-21 q28d); cyclophosphamide 50 mg bid (days 1-21 q28d), and prednisone 50 mg every other day. Treatment was planned for 6 cycles, and responses were assessed on intent-to-treat based on the International Uniform Response Criteria, the investigators noted in a poster presentation during the 52nd American Society of Hematology Annual Meeting and Exposition. Patients who responded chose whether to proceed to observation or transplantation. All patients received aspirin prophylaxis (81 or 325 mg/d) for prevention of deep-vein thrombosis, acyclovir for herpes zoster prevention, and bisphosphonates, unless contraindicated.

Between October 2007 and August 2010, 46 patients were enrolled. Median follow-up was 5.6 months. At this time, 38 patients are evaluable for confirmed responses (ie, off-study or had completed at least 4 cycles of therapy). Median age was 63 years (range, 41-76 years). Eighteen patients had International Staging System stage 2 (42%), and 10 (21%) had stage 3 disease. Median number of cycles was 6 (range, 1-6 cycles).

Among the evaluable patients, overall response rate was 89%: 1 complete response (CR, 5%), 9 very good partial response (VGPR, 26%), and 26 partial response (PR, 58%). Three patients had stable disease (8%) after the first cycle, and treatment is ongoing. One patient had progression (3%). Thirty two of 38 patients have discontinued study treatment. Reasons for treatment discontinuation were study completion per protocol (24), disease progression (3), adverse event (2), noncompliance (1), alternate treatment (1), or withdrawal of consent unrelated to toxicity (1).

The most common toxicity was sensory neuropathy (24%); 8 (21%) grade 1, and 1 (3%), grade 2. Other common toxicities included constipation (21%), pruritus (21%), and edema of limbs (18%). The most common hematologic toxicity was neutropenia (18%); 4 grade 3 and 2 grade 4. Infections were observed 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 hematologic toxicity attributed to lenalidomide or cyclophosphamide. Twenty-five patients had stem cell collection; sufficient numbers of stem cells (CD34+ cells ≥4.0 x 106 cells/kg) were collected for use in transplantation. At the time of analysis, 15 patients have undergone high-dose chemotherapy and stem cell transplantation. Of 8 patients with PR on RCP, 7 achieved VGPR and 1 achieved CR post-transplant. Of 4 patients with VGPR on RCP, 2 achieved CR and 2 remained in VGPR post-transplant. Post-transplant response was not yet evaluable in the 3 remaining patients.