超高危多发性骨髓瘤患者自体干细胞移植的结局

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM).

This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT).

We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by fluorescence in situ hybridization. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Seventy-nine patients with two or more high-risk cytogenetic abnormalities were included in our analysis. The median age of 61 years (range, 33. 5 to 76. 5 years), and 57% were female. Sixty-seven patients had two high-risk cytogenetic abnormalities, and 12 patients had three high-risk cytogenetic abnormalities. The most common combinations of high-risk abnormalities were [1q+, t(4:14)] (n = 25; 32%) and [1q+, del17p] (n = 21; 27%). The majority of patients received either bortezomib, lenalidomide, and dexamethasone (48%) or carfilzomib, lenalidomide, and dexamethasone (16%) as induction therapy.

Prior to autoHCT, 52 patients (66%) achieved a very good partial response or better (≥VGPR), whereas 23 patients (29%) achieved minimal residual disease (MRD)-negative ≥VGPR. Fifty-six patients (71%) received post-transplantation maintenance therapy. Thirty-six patients (46%) achieved MRD-negative ≥VGPR at day +100 after autoHCT, and 40 patients (51%) did so at best post-transplantation response. With a median follow-up in surviving patients of 38. 3 months (range, 11. 9 to 104.

8 months), the median PFS and OS in the entire cohort were 22. 9 months and 71. 5 months, respectively. For the subset of patients with three HR abnormalities, the median PFS was 15. 6 months and median OS was 28. 0 months. In multivariate analysis, achieving MRD-negative ≥VGPR prior to autoHCT was associated with improved PFS (hazard ratio [HR], . 42; P = . 045), whereas male sex (HR, . 15; P = . 009) and achieving MRD-negative ≥VGPR post-autoHCT (HR, . 27; P = . 026) were associated with improved OS.

In conclusion, patients with ultra-high-risk MM have a median PFS of <24 months with the current standard of care that includes consolidation with autoHCT. These patients may benefit from earlier use of newer treatment modalities, such as chimeric antigen receptor T cell therapy and bispecific antibodies.