Outcomes of Single Versus Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience
Authors: Philip Shona , Dehghani Mina , Siqueira Lenicio , Quint Anthony , Lam Selay , Phua Chai Wye , Xenocostas Anargyros , Deotare Uday , Louzada Martha L 
Published: November 2021

Abstract
Introduction: Over the past decade, significant advances in the treatment strategy of newly diagnosed multiple myeloma patients (NDMM) have challenged the initial management strategy in transplant-eligible (TE) patients. The value of a single autologous stem cell transplant (ASCT) is established in standard-risk myeloma; however, the role for tandem ASCT reveals conflicting results, especially in patients with high-risk cytogenetic (HR) features. HR changes include at least one of the cytogenetic lesions: t(4;14), t(14;16), t(14;20), del17p, 1q amp +, 1q amp + del 1p. Subgroup analyses of HR patients in the EMN02 study suggest benefits with tandem ASCT.
Methods: We retrospectively reviewed our single centre ASCT experience in TE NDMM patients with HR from London, Canada, from January 1, 2007, to April 30, 2021 with the primary objective to compare single versus tandem ASCT for patients with high-risk MM. Secondary objectives include progression-free survival (PFS), overall survival (OS) and the effect of maintenance therapy on survival. OS and PFS were estimated using the Kaplan-Meier method. We also applied univariate and multivariate cox regression to assess the effects of age, hemoglobin, and creatinine on survival.
Results: 155 NDMM received at least one ASCT between January 1, 2007 to April 30, 2021. 61/155 (39.3%) patients had HR disease. T(4:14) was seen in 19/61 (31.1%) patients; t(14:16) in 9/61 (9.8%) patients; del 17p in 20/61 (32.7%) patients, 1q amp in 36/61 (59.0%) patients and 1p del + 1q amp in 8/61 (13.1%). Patients with more than one abnormality was seen in 22/61 (36.0%) patients. In this high-risk group, the most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 58/61 patients (95.0%). 34 (55.7%) patients received single ASCT and 27 (44.2%) patients received tandem ASCT. 18/34 (52.9%) single ASCT patients and 15/27 (55.5%) tandem ASCT patients received maintenance therapy. Maintenance therapy included single-agent lenalidomide (imid) in 14/61 (22.9%); single-agent bortezomib or ixazomib (proteasome inhibitor (PI)) in 8/61 (13.1%), and; imid + PI combination in 11/61(18.0%). Baseline characteristics are summarized in Table 1.
Single versus tandem ASCT in HR patients revealed no statistically significant PFS difference at 60 months (p=0.3). Maintenance therapy demonstrated a substantial improvement in PFS regardless of the number of ASCT (single ASCT HR=0.1687, 95% CI range 0.05-0.52, p&lt;0.001) tandem ASCT (HR=0.1319, 95% CI range 0.01-0.96, p=0.019). PFS was similar in patients who did not receive maintenance in tandem ASCT (20 months) or single ASCT (19 months) (p=0.57).
At the 60-month follow-up, the median PFS for high-risk patients without maintenance was 18.8 months. In contrast, the PFS for patients on maintenance was not reached (HR=0.1446, 95% CI range 0.05-0.38, p&lt;0.001). There was no difference in OS (p=0.38) with or without maintenance therapy. When comparing single-agent vs. combination strategy with maintenance, there was no PFS (p=0.47) or OS (p=0.68) difference between strategies. All patients were progression-free in those who received any maintenance at 60 months.
Conclusion: In our single centre experience, single vs. tandem ASCT in TE NDMM with HR disease did not contribute to long-term survival outcomes, but the presence of any maintenance therapy had a more considerable impact on PFS. Our data does show a longer progression-free survival compared to previous published data, which is likely due to our sample size.
Figure 1 Figure 1.

Disclosures
Lam: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.