Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial

Abstract

The combination of lenalidomide and low-dose dexamethasone is an effective treatment for multiple myeloma (MM). Addition of alkylating agents to lenalidomide or thalidomide results in increased response rates and deeper responses. We designed this trial to study the combination of cyclophosphamide, lenalidomide, and dexamethasone (CRd) as initial therapy for MM. Fifty-three patients with previously untreated symptomatic MM was enrolled. Patients received 4-week treatment cycles consisting of lenalidomide (25 mg daily for 3 weeks), dexamethasone (40 mg weekly), and cyclophosphamide (300 mg/m(2) weekly for 3 weeks). A partial response or better was seen in 85% of patients including 47% with a very good partial response or better. The toxicities were manageable with over 80% of planned doses delivered; six patients went off study for toxicity. The median progression free survival (PFS) for the entire group was 28 months (95% CI: 22.7-32.6) and the overall survival (OS) at 2 years was 87% (95% CI: 78-96). Importantly, 14 patients with high-risk MM had similar PFS and OS as the standard-risk patients (n = 39). CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy.

Trial registration: ClinicalTrials.gov NCT00478218.

Conflict of interest statement

Conflict of interest: M.Q.L., S.K.K., J.R.M., and A.D. sponsored research funded by Celgene; S.R.H., F.K.B., P.R.G., J.A.L., S.V.R., S.R.Z., P.L.B., C.B.R., T.E.W., R.F., S.J.R., and D.D. have nothing to disclose relevant to current manuscript. K.S., R.F., and M.A.G. have received consulting fees from Celgene. R.F. has received a patent for the prognostication of M.M. based on genetic categorization of the disease.

Copyright © 2011 Wiley-Liss, Inc.

Figures

Figure 1

Figure presents the actual decrease in the M-protein measurements as a proportion of the baseline values using a waterfall plot of response depth at the end of four cycles of therapy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

A: Figure provides information on the frequency and grade of various toxicities seen across the trial, grouped by patients (n = 53). The maximum grade of an individual toxicity seen in any given patient is presented. If a patient had multiple occurrences of a particular toxicity, only the highest grade is presented. B: Figure provides estimates of frequency and grade of various toxicities seen across all cycles (n = 699) grouped by toxicities. If a patient had multiple occurrences of any particular toxicity, each will be counted. C: Median (interquartile range; IQR) for total white cell count (WBC), ANC, and platelet counts (PLT) during the first 12 cycles of treatment are presented. There is no progressive decline in the counts over the 12 cycles, beyond that seen in the initial cycles, suggesting lack of any cumulative hematological toxicity with the combination of lenalidomide and cyclophosphamide.

Figure 3

A: Figure depicts the Kaplan Meier plots for OS and PFS for all patients enrolled on the study (N = 53). B: Figure depicts the Kaplan Meier plots for OS and PFS for all patients grouped by risk status (mSMART high-risk criteria); 14 patients had high-risk myeloma and 39 patients were considered as standard risk. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]