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Session: Hematologic Malignancies—Plasma Cell Dyscrasia

Type: Oral Abstract Session

Time: Sunday June 2, 9:45 AM to 12:45 PM

Location: E451

E3A06: Randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma.

Multiple Myeloma

Hematologic Malignancies—Plasma Cell Dyscrasia

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr 8001)

Author(s): Sagar Lonial, Susanna J. Jacobus, Matthias Weiss, Shaji Kumar, Robert Z. Orlowski, Jonathan L. Kaufman, Abdulraheem Yacoub, Francis Buadi, Timothy E. O'Brien, Jeffrey Matous, Daniel M. Anderson, Robert Emmons, Madhav V. Dhodapkar, Lynne I. Wagner, S. Vincent Rajkumar; Winship Cancer Institute of Emory University, Atlanta, GA; Dana-Farber Cancer Institute, Boston, MA; ThedaCare, Appleton, WI; Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Kansas Cancer Center, Westwood, KS; Division of Hematology, Mayo Clinic, Rochester, MN; MetroHealth Medical Center/Case Western Reserve University School of Medicine, Cleveland, OH; Colorado Blood Cancer Institute, Denver, CO; Regions Hospital, St Paul, MN; Ochsner Cancer Institute, New Orleans, LA; Yale School of Medicine, New Haven, CT; Northwestern University Feinberg School of Medicine, Chicago, IL

Abstract Disclosures


Background: Smoldering multiple myeloma (SMM) is a precursor to myeloma, wherein current standard of care is observation (obs). Data from a randomized Spanish trial (Mateos et al, NEJM 2015) suggest that lenalidomide(len)/dexamethasone improves time to developing myeloma (TTP) and overall survival (OS) for patients (pts) with high risk (HR) SMM over obs. However, pts were not screened with advanced imaging techniques, used a HR definition that is not routinely available, and combination therapy limited the ability to isolate the effect of len, and thus has not become standard of care. Methods: E3A06 is a randomized phase III intergroup trial, testing the effect of single agent len compared with obs for pts with intermediate or high risk SMM. In an initial phase II run in all pts received len to demonstrate safety. Eligibility required ≥10% PCs and abnormal serum FLC ratio (<0.26 or >1.65). The primary endpoint was progression PFS was estimated by the Kaplan-Meier method and compared using the one-sided stratified log-rank test. Results: PII enrolled 44 pts and PIII randomized 182 pts to either len (n=90) or obs (n=92) [stratified on time since SMM diagnosis ≤1y vs >1y]. Baseline characteristics were similar between the arms. 80% (PII) and 51% (PIII) are off len, primarily due to adverse events (AE) or pt withdrawal. Among the len treated pts, G3/4 non-hematologic AE occurred in 28% of PIII pts with fatigue being most common (n=5). G4 hematologic AE rate was 5.7%, primarily neutropenia (n=4). 3-year cumulative incidence of invasive SPMs was 5.2% (len) and 3.5% (obs). Overall response rate was 47.7% for the phase II study, and in phase III, 48.9% for the len arm, and 0% for the obs arm. Median follow up was 71 months (PII), and 28 months (PIII). 3-year PFS was 87% for the PII cohort. One, 2 and 3-year PFS was 98%, 93%, and 91% for len, and 89%, 76%, and 66% for the obs arm (HR 0.28, p=0.0005) favoring the len arm. No difference in QOL score was noted between arms. Conclusions: Overall, this trial represents the largest randomized trial in SMM to date. In conjunction with the Spanish data, this trial may support a change in clinical practice. Clinical trial information: NCT01169337

Phase 2 PFS
1 yr0.98
3 yr0.87
5 yr0.78
Phase 3 PFSLenObs
1 yr0.980.89
2 yr0.930.76
3 yr0.910.66

Other Abstracts in this Sub-Category:


1. Updated risk stratification model for smoldering multiple myeloma (SMM) incorporating the revised IMWG diagnostic criteria.

Meeting: 2019 ASCO Annual Meeting Abstract No: 8000 First Author: Jesus San Miguel
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma


2. Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: Results from the FORTE trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 8002 First Author: Francesca Gay
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma


3. Phase 3 randomized study of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 1 results.

Meeting: 2019 ASCO Annual Meeting Abstract No: 8003 First Author: Philippe Moreau
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma