In a pooled analysis reported in the journal Bone Marrow Transplantation, Costa et al found that autologous followed by reduced-intensity conditioning allogeneic hematopoietic cell transplantation (auto-allo) was associated with longer overall survival compared with tandem autologous transplantation (auto-auto) in patients with newly diagnosed multiple myeloma.

As noted by the authors, unlike auto-auto transplantation, auto-allo transplantation offers a graft-vs-myeloma effect but is associated with greater toxicity.    

Study Details

The analysis included individual patient data from a total of 1,338 patients from four trials that compared auto-auto transplantation and auto-allo transplantation. The trials enrolled patients between 1998 and 2007. In all trials, patients were allocated to auto-auto or auto-allo transplantation based exclusively on the availability or lack of availability of a human leukocyte antigen (HLA)-identical matched sibling donor.

For the pooled analysis, there were 899 patients in the auto-auto group and 439 patients in the auto-allo group. Median follow-up of survivors was 118.5 months. Outcomes were assessed on an intent-to-treat basis. Overall, the study treatment assigned in the four trials was completed in 56% of the auto-auto group and 73% of the auto-allo group.

Key Findings

A complete response was achieved by 40.0% of patients in the auto-auto group vs 54.9% of the auto-allo group. The risk of nonrelapse mortality was reduced in the auto-auto vs auto-allo group (P < .001), with 5-year rates of 6.9% vs 17.4% and 10-year rates of 8.3% vs 19.7%. The risk of relapse or disease progression was greater in the auto-auto group vs auto-allo group, with 5-year rates of 69.7% vs 52.4% (P < .001) and 10-year rates of 77.2% vs 61.6% (P < .001).

Progression-free survival was improved in the auto-allo group (hazard ratio [HR] = 0.85, P = .004). Median progression-free survival was 24.4 months in the auto-allo group vs 26.4 months in the auto-auto group, with 5-year rates of 30.1% vs 23.4% (P = .010) and 10-year rates of 18.7% vs 14.4% (P = .060).

Overall survival was improved in the auto-allo vs auto-auto group (HR = 0.84, P = .02). Median overall survival was 98.3 months in auto-allo group vs 78.0 months in the auto-auto group, with 5-year rates of 62.3% vs 59.8% (P = .370) and 10-year rates of 44.1% vs 36.4% (P = .010).

Among high-risk patients, median progression-free survival was 21.5 months in auto-allo group vs 22.9 months in auto-auto group, with 5-year rates of 31.5% vs 17.0% (P = .015) and 10-year rates of 22.3% vs 8.9% (P = .008). Median overall survival was 73.2 vs 64.4 months, with 5-year rates of 51.7% vs 50.8% (P = .897) and 10-year rates of 39.0% vs 28.6% (P = .120).

Patients in auto-allo group had improved postrelapse survival (HR = 0.71, P < .001).  Median postrelapse survival was 62.3 months in the auto-allo group vs 41.5 months in the auto-auto group, with 5-year rates of 51.1% vs 37.0% (P < .001).

The investigators summarized: “The present study stresses the need for long-term follow-up in trials appraising transplant strategies in multiple myeloma. This combined analysis with long-term follow-up confirms the existence of meaningful graft-versus-myeloma effect that prevents and delays progression, improves outcomes postrelapse, improves overall survival, and may lead to cure in a subset of patients. This analysis does not inform what subsets of patients, if any, would currently benefit from an upfront auto-allo strategy given the multiplication of treatment options since these trials were designed and conducted. It also does not indicate whether the potential benefit in overall survival would justify the morbidity and impairment in quality of life expected from graft-versus-host disease or how the presented auto-allo strategy would compare with modern induction and maintenance strategies that lead to higher 10-year overall survival than presented in either arm of the present analysis.”

They further noted, “Instead, the findings invite continuous exploration of allogeneic transplantation in multiple myeloma with approaches such as use of posttransplantation cyclophosphamide…unrelated and related haploidentical donors, and the deployment of new multiple myeloma immunotherapeutic agents as post-allogeneic hematopoietic cell transplantation maintenance strategy.”

Luciano J. Costa, MD, PhD, of the University of Alabama at Birmingham, is the corresponding author for the Bone Marrow Transplantation article.

Disclosure: Support for the study was provided to the Blood and Marrow Transplant Clinical Trials Network by a grant from the National Heart, Lung, and Blood Institute and the National Cancer Institute, along with funding from the Southwest Oncology Group. For full disclosures of the study authors, visit nature.com.