Abstract
Background Graft-versus-myeloma (GvM) effect from allogeneic-SCT potentially affords long-term disease control in multiple myeloma (MM). A salvage program incorporating chemotherapy followed by tandem autologous + non-myeloablative allogeneic-SCT (TAA-SCT) may offer a survival advantage over chemotherapy alone (ChA) Method Consecutive patients with relapsed MM (R-MM) salvaged with chemotherapy followed by TAA-SCT at the Alfred between Jan-08 and Dec-19 were identified. A 2:1 comparator cohort salvaged with ChA (iMiD agent/PI available) matched for age/sex/ISS-stage, was extracted from the Myeloma and Related Diseases Registry (MRDR). All patients received autologous-SCT as part of their upfront treatment. Survival was assessed by Kaplan-Meier method and compared using log-rank test. Prognostic variables were adjusted using Cox-regression. Results 48 patients received TAA-SCT following salvage chemotherapy during the study period; 35% met criteria for high-risk myeloma at diagnosis (ISS-III and/or adverse CG/FISH) with a median age at salvage of 57 [range: 32-68] and 2 prior therapy lines [range: 1-7]. Preceding TAA-SCT, salvage chemotherapy yielded ≥ PR in ~95% of cases; iMiD® and/or PI were used in ~85%. 87 matched patients were identified from the MRDR as the ChA cohort. Baseline characteristics were comparable, except that the TAA-SCT cohort was more heavily pre-treated (p < 0.001). With a median follow-up of 60 months, the estimated 5-year OS were similar: TAA-SCT 63% (95%CI: 48%-75%) vs. ChA 53% (95%CI: 34%-68%). However, after adjusting for number of prior therapy lines, an OS advantage was observed in the TAA-SCT relative to the ChA cohort (HR 0.33, 95% CI:0.13-0.82, p = 0.001). In addition, PFS was also improved in the TAA-SCT cohort (Figure 1, p < 0.001), with a 5-year PFS of 25% (95%CI: 14%-38%) vs. 1% (95%CI: 0-6%) for the ChA cohort. Conclusion In the iMiD® and PI era, TAA-SCT following chemotherapy remains an effective salvage strategy in selected patients with R-MM, providing an immunological platform for a GvM effect with OS and PFS advantage over chemotherapy alone. Graft-versus-myeloma (GvM) effect from allogeneic-SCT potentially affords long-term disease control in multiple myeloma (MM). A salvage program incorporating chemotherapy followed by tandem autologous + non-myeloablative allogeneic-SCT (TAA-SCT) may offer a survival advantage over chemotherapy alone (ChA) Consecutive patients with relapsed MM (R-MM) salvaged with chemotherapy followed by TAA-SCT at the Alfred between Jan-08 and Dec-19 were identified. A 2:1 comparator cohort salvaged with ChA (iMiD agent/PI available) matched for age/sex/ISS-stage, was extracted from the Myeloma and Related Diseases Registry (MRDR). All patients received autologous-SCT as part of their upfront treatment. Survival was assessed by Kaplan-Meier method and compared using log-rank test. Prognostic variables were adjusted using Cox-regression. 48 patients received TAA-SCT following salvage chemotherapy during the study period; 35% met criteria for high-risk myeloma at diagnosis (ISS-III and/or adverse CG/FISH) with a median age at salvage of 57 [range: 32-68] and 2 prior therapy lines [range: 1-7]. Preceding TAA-SCT, salvage chemotherapy yielded ≥ PR in ~95% of cases; iMiD® and/or PI were used in ~85%. 87 matched patients were identified from the MRDR as the ChA cohort. Baseline characteristics were comparable, except that the TAA-SCT cohort was more heavily pre-treated (p < 0.001). With a median follow-up of 60 months, the estimated 5-year OS were similar: TAA-SCT 63% (95%CI: 48%-75%) vs. ChA 53% (95%CI: 34%-68%). However, after adjusting for number of prior therapy lines, an OS advantage was observed in the TAA-SCT relative to the ChA cohort (HR 0.33, 95% CI:0.13-0.82, p = 0.001). In addition, PFS was also improved in the TAA-SCT cohort (Figure 1, p < 0.001), with a 5-year PFS of 25% (95%CI: 14%-38%) vs. 1% (95%CI: 0-6%) for the ChA cohort. In the iMiD® and PI era, TAA-SCT following chemotherapy remains an effective salvage strategy in selected patients with R-MM, providing an immunological platform for a GvM effect with OS and PFS advantage over chemotherapy alone.
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