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Autologous Stem Cell Transplantation for Large B-cell Lymphoma with Secondary Central Nervous System Involvement
Akin, S., Hosing, C., Khouri, I. F., Ahmed, S., Alousi, A., Fowler, N. H., Joseph, J., Truxillo, J., Ramdial, J., Maadani, F., et al
Blood advances. 2022
Abstract
Secondary central nervous system large B-cell lymphoma (SCNSL) is rare with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal LDH, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (HR 0.278, 95% CI: 0.153-0.506; p=<0.0001) and ≤ 2 prior lines of therapy (HR 0.485, 95% CI: 0.274-0.859; p=0.0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR 0.352, 95% CI: 0.186-0.663; p=0.0013) and ≤ 2 prior lines of therapy (HR 0.476, 95% CI: 0.257-0.882; p=0.0183) were associated with improved survival. In the largest single center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those received less than two lines of therapy have particularly excellent outcomes.
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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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5.
Impact of renal impairment on light chain amyloidosis outcomes after autologous hematopoietic stem cell transplantation
Srour, S. A., Qazilbash, M. H.
Annals of translational medicine. 2020;8(7):509
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A randomized phase II study of standard-dose versus high-dose rituximab with BEAM in autologous stem cell transplantation for relapsed aggressive B-cell non-hodgkin lymphomas: long term results
Srour, S. A., Li, S., Popat, U. R., Qazilbash, M. H., Lozano-Cerrada, S., Maadani, F., Alousi, A., Kebriaei, P., Anderlini, P., Nieto, Y., et al
British Journal of Haematology. 2017;178(4):561-570
Abstract
High-dose rituximab (HD-R) combined with carmustine, cytarabine, etoposide and melphalan (BEAM) and autologous stem cell transplant (ASCT) was effective and tolerable in a single-arm prospective study of relapsed aggressive B-cell non-Hodgkin lymphoma (R-NHL). We performed a randomized phase 2 study comparing HD-R versus standard-dose rituximab (SD-R) in R-NHL. Ninety-three patients were randomized to HD-R (1000 mg/m2 ) (n = 42) or SD-R (375 mg/m2 ) (n = 51) administered on post-transplant days +1 and +8, using a Bayesian adaptive algorithm. The 2 treatment arms were balanced in regards to patient demographic and clinical characteristics. At a median follow-up of 7.92 years, the 5-year disease-free survival (DFS) and overall survival (OS) were 40% and 48%, respectively. We found no statistically significant differences between HD-R and SD-R in 5-year DFS (36% vs. 43%; P = 0.205) and OS (43% vs. 52%; P = 0.392). In multivariate analyses, only disease status before ASCT [residual disease versus complete remission (CR)] (hazard ratio [HR] 1.79, 95% confidence interval [CI]: 1.08-2.95) and number of prior treatments received (>2 vs. <=2 lines of treatment) (HR 1.89, 95% CI: 1.13-3.18) were associated with worse DFS and OS. Patients who had SCT while in CR or who received <=2 lines of treatment prior to SCT had better 5-year OS (57% vs. 35%; P = 0.02 and 54% vs. 30%, P = 0.001, respectively) in both arms. No differences in engraftments or adverse events were noted in the 2 arms. When combined with BEAM and ASCT in relapsed aggressive B-cell NHL, HD-R provided no DFS or OS advantage over SD-R. In patients who have been exposed to rituximab in the frontline or salvage setting, the addition of rituximab in the peri-transplant setting remains controversial.