P-339: Tandem autologous transplantation can overcome the poor prognosis of double-hit multiple myeloma patients with 1q21 gain/amp and t(4;14)

Introduction: Novel drugs induction followed by autologous stem cell transplantation (ASCT) is the standard regimen for transplant-eligible patients with multiple myeloma (MM). However, approximately 20% of patients will have early relapse within 18 months after ASCT, which are defined as high-risk myeloma. Despite the fact that ASCT has become an important means to improve the prognosis of MM patients, further research is still needed to improve the outcome of high-risk patients, especially "double-hit" MM patients. Some studies suggest that tandem ASCT may overcome the poor prognosis of high-risk myeloma. But which type of high-risk MM patients may really benefit from tandem ASCT remains inconclusive.

Methods: In this study, we enrolled 30 cytogenetic high-risk (including t(4;14), t(14;16), 17p- and 1q21 gain/amp) myeloma patients who underwent tandem ASCT. Another 53 cytogenetic high-risk patients who received single ASCT in the same period were enrolled as the control group. The differences in time-to-progression survival (TTP; primary endpoint) and overall survival (OS) between the two groups were estimated using the Kaplan-Meier method. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR2100046510.

Results: Kaplan-Meier estimates of TTP (not reach and 47.9 months, p=0.036) and OS (not reach and 62.5 months, p=0.039) were better in tandem ASCT group compared with single ASCT group. There was no significant difference in treatment-related mortality (TRM) between the two groups (p=0.64). Subgroup analysis showed that for patients with a single high-risk cytogenetic abnormality, there was no statistically significant difference in PFS (NR and 49.0 months, p=0.924) and OS (p=0.415) between those who received tandem transplantation and those who received single transplantation. Double-hit patients who underwent tandem transplantation had better PFS than those who underwent single transplantation (NR and 35.7 months, p=0.038), but there was no statistically significant difference in OS (p=0.881). Among them, patients with the double-hit of 1q21 gain/amp and t(4;14) who received tandem transplantation had better PFS (44.2 months and NR, p=0.924) than those who received single transplantation, while there was no statistically significant difference in PFS (27.5 months and 35.7 months, p=0.596) between patients receiving tandem or single transplantation for other double-hit MM patients.

Conclusions: Tandem ASCT can overcome the poor prognosis of double-hit multiple myeloma patients, especially those with the double-hit of 1q21 gain/amp and t(4;14).