Long-Term Follow-Up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma

Abstract

Purpose: The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a highly effective and convenient induction regimen for both transplantation-eligible and -ineligible patients with myeloma. Here, we present the largest cohort of patients consecutively treated with RVD induction therapy followed by risk-adapted maintenance therapy with the longest follow-up and important information on long-term outcomes.

Patients and methods: We describe 1,000 consecutive patients with newly diagnosed myeloma treated with RVD induction therapy from January 2007 until August 2016. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria.

Results: The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively.

Conclusion: RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes. This study includes the largest cohort of patients treated with RVD reported to date with long follow-up and demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.

FIG 1.

CONSORT diagram. ASCT, autologous stem-cell transplantation; ASCT1, first autologous stem-cell transplantation; IMID, immunomodulatory drug; NDMM, newly diagnosed multiple myeloma; PI, proteasome inhibitor; RVD, lenalidomide, bortezomib, and dexamethasone.

FIG 2.

Response rates to lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy (evaluable patients, n = 977). ASCT, autologous stem-cell transplantation; CR, complete response; ORR, overall response rate; PD, progressive disease; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response. (^a) Seven hundred forty-two evaluable patients of 751 patients who underwent up-front transplantation.

FIG 3.

(A) Progression-free survival (PFS) by postinduction very good partial response (VGPR) status. (B) Overall survival (OS) by postinduction VGPR status. (C) PFS by Revised International Staging System (R-ISS) stage. (D) OS by R-ISS stage.

FIG 4.

(A) Progression-free survival (PFS) of entire cohort. (B) Overall survival (OS) of entire cohort. (C) PFS by risk. (D) OS by risk.