In a pooled analysis reported in Bone Marrow Transplantation,1 Luciano J. Costa, MD, PhD, of the University of Alabama at Birmingham, and colleagues found that autologous hematopoietic cell transplantation followed by reduced-intensity conditioning allogeneic 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.
Luciano J. Costa, MD, PhD
Study Details
The analysis included individual patient data from a total of 1,338 patients enrolled in four trials comparing auto-auto transplantation vs auto-allo transplantation, from 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–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 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).
KEY POINTS
- Complete response was achieved by 40.0% of patients with myeloma undergoing auto-auto transplant vs 54.9% of those receiving auto-allo transplant.
- The risk of nonrelapse mortality was reduced in the auto-auto vs auto-allo group, and the risk of relapse or disease progression was greater in the auto-auto group vs auto-allo group.
- Patients who received auto-allo have improved post relapse survival indicating synergy between graft-versus-myeloma effect and anti-myeloma gents.
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 also improved in the auto-allo vs auto-auto group (HR = 0.84, P = .02). Median overall survival was 98.3 months in the 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 the auto-allo group vs 22.9 months in the 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 the 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).
Implications and Conclusions
“[T]he present study stresses the need for long-term follow-up in trials appraising transplant strategies in [multiple myeloma].”— Luciano J. Costa, MD, PhD
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The investigators summarized: “[T]he 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 a meaningful [graft-vs-myeloma] effect that prevents and delays [disease] progression, improves outcomes postrelapse, improves [overall survival], and may lead to cure in a subset
of patients.”
They continued: “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-vs-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 note, “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.”
“[T]he findings invite continuous exploration of allogeneic transplantation in [multiple myeloma]….”— Luciano J. Costa, MD, PhD
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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. Dr. Costa has served as a consultant for Karyopharm, Celgene, Amgen, Sanofi, AbbVie, and GSK; has received research funding from Amgen and Janssen; and has received honoraria from Celgene Janssen, and Amgen.
REFERENCE
1. Costa LJ, Iacobelli S, Pasquini MC, et al: Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation. Bone Marrow Transplant. April 14, 2020 (early release online).
