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

Nisha S. Joseph, MD; Jonathan L. Kaufman, MD; Madhav V. Dhodapkar, MD; Craig C. Hofmeister, MD, MPH; Dhwani K. Almaula, MBBS, MPH; Leonard T. Heffner, MD; Vikas A. Gupta, MD, PhD; Lawrence H. Boise, PhD; Sagar Lonial, MD; and Ajay K. Nooka, MD, MPH

Disclosures

J Clin Oncol. 2020;38(17):1928-1937. 

In This Article

Abstract and Introduction

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.

Introduction

There have been significant therapeutic advances in myeloma over the past few decades, leading to an improved survival benefit for patients during this period. The availability of novel classes of drugs, namely immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs), and the increased use of autologous stem-cell transplantation (ASCT) and continuous maintenance therapy have contributed to these sustained responses.

Improvements in pre- and post-ASCT outcomes have been a result of the evolution toward the use of carefully crafted combination therapy required for newly diagnosed myeloma. Several trials have demonstrated improvements in progression-free survival (PFS) for 3-drug regimens over 2-drug regimens, both with and without the use of high-dose therapy as consolidation. However, in nearly all cases, the duration of PFS has been longer with ASCT consolidation. The widespread adoption of the lenalidomide, borte-zomib, and dexamethasone (RVD) induction regimen has changed the expectation for induction regimens and has been validated with several large phase III trials, although the follow-up on these trials is relatively short. Furthermore, the type of maintenance therapy used and the duration of maintenance (continuous v limited duration) also vary in these trials using RVD for induction, limiting accurate estimation of long-term outcomes. In this analysis, we describe a consecutive cohort of 1,000 patients treated uniformly with long-term follow-up. We describe outcomes based on genetic risk at diagnosis, PFS, overall survival (OS), and the impact of genetics on the quality and depth of response, thus providing a more comprehensive picture of the overall treatment course with RVD as induction therapy.

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