Autologous Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Therapies

Ricardo D. Parrondo, MD; Sikander Ailawadhi, MD; Taimur Sher, MD; Asher A. Chanan-Khan, MD; Vivek Roy, MD


J Oncol Pract. 2020;16(2):56-66. 

In This Article

Single ASCT Versus Tandem ASCT

Tandem ASCT is defined as a preplanned second ASCT within 6 months of the first ASCT. A meta-analysis performed on studies that evaluated the role of tandem ASCT before the era of novel agent induction therapies did not demonstrate any PFS or OS benefit with tandem ASCT compared with single ASCT.[34] In patients with high-risk cytogenetics [t(4;14) and/or del17p] who had not achieved a complete response after bortezomib-based induction therapy, tandem ASCT conferred PFS (41 v 20 months; HR, 0.52; P =. 003) and OS advantages (67 v 31.5 months; HR, 0.32; P < .001) compared with single ASCT, respectively.[35] In the EMN02/HO95 trial, patients received four cycles of VCD induction therapy followed by random assignment to either V-melphalan-prednisone (VMP) intensification or single or tandem ASCT. On an intention-to-treat basis, 3-year PFS was 73%for tandem ASCT versus 64%for single ASCT (HR, 0.70; 95% CI, 0.50 to 0.98; P = .040). Risk of progression was reduced in patients with high-risk cytogenetics who underwent tandem ASCT (HR, 0.42; 95% CI, 0.21 to 0.84; P = .014). Three-year OS was also prolonged in patients who underwent tandem ASCT compared with single ASCT (89% v 82%; HR, 0.52; 95% CI, 0.31 to 0.86; P = .011). Risk of death was reduced in patients with high-risk cytogenetics who received tandem ASCT (HR, 0.52; 95% CI, 0.28 to 0.98; P = .042).[36]

The aforementioned tandem ASCT studies were performed in Europe where VMP/VCD were commonly used induction regimens; however, in the United States, the most commonly used induction regimens combine both a proteasome inhibitor and an immunomodulatory agent—mainly VRD—which result in deeper hematologic responses and PFS when combined with ASCT. In the prospective phase III BMT-CTN 0702 STAMINA trial that was conducted in the United States, 55% of patients received VRD induction—for 2 to 12 months—followed by ASCT and were then randomly assigned to either tandem ASCT, consolidation with four cycles of VRD, or lenalidomide maintenance alone. No differences were observed in the depth of response, PFS, or OS among the three treatment arms. Patients with high-risk cytogenetics did not gain a PFS or OS advantage with the use of tandem ASCT.[37] It is plausible that the use of two novel agents—proteasome inhibitor and immunomodulatory agent—in induction therapy abrogates the need for a tandem ASCT, even in patients with high-risk cytogenetics. At this time, despite conflicting data, tandem ASCT may be beneficial for patients with high-risk cytogenetics. Clinical trials are ongoing that test the role of tandem ASCT with other novel anti-MM agents (Table 2).