Comparison of Outcomes of Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Three Different Conditioning Regimens

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with multiple myeloma, as it provides a graft-versus-myeloma effect alongside a myeloma-free graft. Although reduced-intensity conditioning regimens decrease nonrelapse mortality (NRM), there is a paucity of data with regard to the ideal conditioning regimen in myeloma. We conducted a retrospective comparison of 3 different preparative regimens used for allo-HCT for multiple myeloma at our institution in recent clinical trials: busulfan/fludarabine (BuFlu), fludarabine/ melphalan 100 mg/m 2 (FM100), and fludarabine/melphalan 140 mg/m 2 (FM140). NRM, progression-free survival (PFS) at 3 years, and overall survival (OS) at 3 years were the primary endpoints. Secondary endpoints included time to engraftment, and the incidence of grades II through IV acute graft-versus-host disease and chronic graftversus-host disease. A total of 73 patients received allo-HCT with these regimens. NRM at 3 years was seen in 3 (21%), 5 (28%), and 6 (24%) patients in the BuFlu, FM100, and FM140 groups, respectively. Three-year PFS in the BuFlu, FM100, and FM140 groups was 16% (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.6 to 2.1), 26% (HR, 0.6; 95% CI, 0.3 to 1.2), and 11% (reference), respectively. Three-year OS in the BuFlu, FM100, and FM140 groups was 39% (HR, 1.1; 95% CI, 0.5 to 2.2), 43% (HR, 0.7; 95% CI, 0.3 to 1.4), and 32% (reference), respectively. High-risk cytogenetics and relapsed disease prior to allo-HCT were found to be independent predictors of inferior OS on multivariate analysis, with a HR of 2.1 (P = .02) and 2.6 (P = .004), respectively. In contrast, the preparative regimen did not emerge as a predictor of PFS or OS. Durable clinical remission can be achieved in 11% to 25% of patients with multiple myeloma with the use of allo-HCT without any significant difference in the safety or efficacy of the conditioning regimen. High-risk cytogenetics and relapsed disease prior to transplant were associated with inferior PFS and OS.

Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

“…Our observation of aGVHD incidence of 24%, the detrimental effect of aGVHD, and the beneficial effect of cGVHD on the outcome of the patients is in line with several previous studies [12,32,39]. For cGVHD, the rate of 62% in our study was in the upper range compared with 27-67% reported elsewhere [16,31,39,40]. This translated to the GRFS median of less than a year.…”

“…We were able to define cytogenetic risk according to current criteria [ 21 ] for less than half of the patients, approximately one-third of them with HR cytogenetics. Several studies have shown that allo-SCT could overcome the adverse prognosis of high cytogenetic risk [ 6 , 11 – 14 ], while others have not [ 15 , 16 ]. In our study, allo-SCT did not seem to benefit patients with HR cytogenetics despite a majority of them receiving allo-SCT in an upfront setting.…”

“…However, a proportion of patients seem to remain in long-term remission [3,6,8]. It is also unclear, whether the graft-versus-myeloma effect of allo-SCT [10] can overcome the poor prognosis of high-risk (HR) patients [11][12][13][14][15][16].…”

Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…However, long-term side effects of allo-SCT widely vary between individual patients and have to be seen as a dynamic process with changing burden of symptoms [ 47 ]. Thus, depending on the timepoint of symptom assessment, the rate of chronic GvHD of any grade ranges from 22% to 67% in different trials [ 17 , 24 , 37 , 44 , 48 , 49 ].…”

Hematopoietic stem cell transplantation for blood cancers in the era of precision medicine and immunotherapy

“…However, this intensive approach consistently was found to be associated with high rates of treatment‐related mortality (35%‐55%), which abrogated any benefits derived from improved disease control. Several recent small studies have evaluated less intensive, but still myeloablative, regimens and have demonstrated 3‐year OS rates of approximately 30% and 1‐year treatment‐related mortality rates of 19% to 37% . To the best of our knowledge, no contemporary systematic studies have evaluated more recent approaches to myeloablative conditioning.…”