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KRD vs. VRD as induction before autologous hematopoietic progenitor cell transplantation for high-risk multiple myeloma
Gaballa, M. R., Ma, J., Rauf, M., Bassett, R., Pasvolsky, O., Tanner, M. R., Bashir, Q., Srour, S. A., Saini, N., Ramdial, J., et al
Bone marrow transplantation. 2022
Abstract
Bortezomib, lenalidomide, and dexamethasone (VRD) induction is standard prior to autologous hematopoietic cell transplantation (auto-HCT) in newly diagnosed, high-risk multiple myeloma (ND-HRMM). Carfilzomib (K) is another proteasome inhibitor approved for MM. In this single-center, retrospective analysis, we compared outcomes in ND-HRMM with pre-transplant KRD or VRD induction. High-risk was defined by t(4:14), t(14:16), 1q21 gain/amplification, or del(17p). Primary endpoints were progression-free (PFS) and overall survival (OS). Of 121 ND-HRMM patients, 63 received KRD, and 58 received VRD. Post-induction, complete (CR), very good partial (VGPR), partial response (PR), and overall response (ORR) rates were 23.8%/49.2%/25.4%/98.4% with KRD, and 19%/46.6%/27.6%/93.1% with VRD. At day 100 post-auto-HCT, these were 38.1%/42.9%/19%/100% with KRD, versus 35.1%/49.1%/12.3%/94.8% with VRD. Pre-auto-HCT, 11 (18.3%) KRD and 7 (12.5%) VRD patients had minimal residual disease (MRD)-negative CR (p = 0.45). Post-auto-HCT, 14 (41.2%) and 13 (43.3%) patients had MRD-negative CR (p = 1.000). Median PFS was 38.2 (95%CI 28.7-NA) and 45.9 months (95%CI 43.2-NA) for KRD and VRD, respectively (p = 0.25). Respective 3-year PFS and OS were 53.5% (95%CI 41.1-69.6) and 95.2% (95%CI 90-100) for KRD and 64% (95%CI 51.6-79.5) and 84.2% (95%CI 73.5-96.3, p = 0.30) for VRD. Overall, KRD induction pre-auto-HCT does not improve outcomes. Prospective, randomized studies are needed to confirm these findings.
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Real-world long-term outcomes in multiple myeloma with VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance
Gaballa, M. R., Ma, J., Tanner, M. R., Al-Juhaishi, T., Bashir, Q., Srour, S. A., Saini, N. Y., Ramdial, J. L., Nieto, Y., Murphy, R., et al
Leukemia & lymphoma. 2022;63(3):710-721
Abstract
Standard-of-care for newly-diagnosed, autologous hematopoietic stem cell transplantation (auto-HCT)-eligible, multiple myeloma (MM) patients includes bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by melphalan 200 mg/m(2) (Mel200)-conditioned auto-HCT and lenalidomide maintenance. We completed a retrospective case series assessing outcomes of 187 MM patients who received this regimen at our institution. The 100-day non-relapse mortality incidence was zero. Before auto-HCT, 9.6 and 52.9% of patients achieved a complete response (CR) or ≥ very good partial response (VGPR), respectively. At day-100 post-transplant, 29.4 and 74.9% had achieved a CR/stringent-CR (sCR) or ≥ VGPR, respectively. At the last evaluation, 57.2% of patients had CR/sCR and 87.1% had ≥ VGPR. Median follow-up, progression-free survival (PFS), and overall survival (OS) were 63.2, 50, and 101.7 months, respectively. The 5-year PFS and OS were 43.1 and 79%. High-risk cytogenetics was associated with worse outcomes. This study illustrates that VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance are associated with good outcomes in MM.
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Melphalan dose intensity for autologous stem cell transplantation in multiple myeloma
Srour, S. A., Milton, D. R., Bashir, Q., Nieto, Y., Saini, N., Daher, M., Ramdial, J., Im, J., Hosing, C., Delgado, R., et al
Haematologica. 2021
Abstract
Not available.
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4.
Comparison of Outcomes of Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Three Different Conditioning Regimens
Maymani, H., Lin, P., Saliba, R. M., Popat, U., Bashir, Q., Shah, N., Patel, K., Parmar, S., Kebriaei, P., Hosing, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
BACKGROUND Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative therapy for patients with multiple myeloma as it provides graft-versus-myeloma effect alongside a myeloma-free graft. Although reduced-intensity conditioning regimens decrease non-relapse mortality (NRM), there is a paucity of data with regard to the ideal conditioning regimen in myeloma. METHODS We conducted a retrospective comparison of three different preparative regimens used for allo-HCT for multiple myeloma at our institution in recent clinical trials: Busulfan/Fludarabine (BuFlu), Fludarabine /Melphalan 100mg/m2 (FM100), and Fludarabine/Melphalan 140mg/m2 (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 grade II-IV acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD). RESULTS 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 BuFlu, FM100 and FM140, respectively. Three-year PFS in the BuFlu, FM100 and FM140 groups was 16% (HR 1.2; 95% CI 0.6-2.1), 26% (HR 0.6; 95% CI 0.3-1.2), and 11% (ref), respectively. Three-year OS in the BuFlu, FM100 and FM140 groups was 39% (HR 1.1; 95% CI 0.5-2.2), 43% (HR 0.7; 95% CI 0.3-1.4), and 32% (ref), respectively. High-risk cytogenetics and relapsed disease prior to allo-HCT were found to be independent predictors of inferior OS on multivariate analysis, with HR of 2.1 (P=0.02) and 2.6 (P=0.004), respectively. In contrast, the preparative regimen did not emerge as a predictor of PFS or OS. CONCLUSIONS Durable clinical remission can be achieved in 11-25% of patients 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.