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1.
Eltrombopag improves platelet engraftment after haploidentical bone marrow transplantation: Results of a Phase II study
Ahmed, S., Bashir, Q., Bassett, R. L., Jr., Ullah, F., Aung, F., Valdez, B. C., Alousi, A. M., Hosing, C., Kebriaei, P., Khouri, I., et al
American journal of hematology. 2024
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Editor's Choice
Abstract
Slow platelet recovery frequently occurs after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with bone marrow graft and post-transplant cyclophosphamide (PCy)-based graft-versus-host disease (GVHD) prophylaxis. Improved platelet recovery may reduce the need for transfusions and improve outcomes. We investigated the safety and efficacy of eltrombopag, a thrombopoietin receptor agonist, at enhancing platelet recovery post-haplo-HSCT. The prospective study included patients ≥18 years of age who received haplo-HSCT with bone marrow graft and PCy. Patients received eltrombopag 300 mg/day starting on Day +5. The primary objective was to estimate platelet engraftment (>50 000/μL by Day 60). In a post hoc analysis, they were compared to a contemporary matched control group who did not receive eltrombopag. One hundred ten patients were included in the analysis (30 eltrombopag and 80 control). Seventy-three percent and 50% of patients in the eltrombopag group and control group, respectively, attained >50 000/μL platelet count by Day 60 (p = .043). No eltrombopag-related grade ≥4 adverse events were observed. Median time to platelet recovery (>20 000/μL) was 29 days with eltrombopag and 31 days for controls (p = .022), while its cumulative incidence was 90% (95% confidence interval [CI]: 78%-100%) with eltrombopag versus 67.5% (95% CI: 57%-78%) for controls (p = .014). Number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and non-relapse mortality were similar between groups. Overall, eltrombopag is safe and improves platelet recovery in patients undergoing haplo-HSCT with bone marrow graft and PCy.
PICO Summary
Population
Adults underoing haploidentical transplant with bone marrow graft and post-transplant cyclophosphamide from a single centre in USA (n=110)
Intervention
Eltrombopag 300 mg/day starting on Day +5 (n=30)
Comparison
contemporary matched control group who did not receive eltrombopag (n=80)
Outcome
Seventy-three percent and 50% of patients in the eltrombopag group and control group, respectively, attained >50 000/μL platelet count by Day 60. No eltrombopag-related grade ≥4 adverse events were observed. Median time to platelet recovery (>20 000/μL) was 29 days with eltrombopag and 31 days for controls, while its cumulative incidence was 90% (95% confidence interval [CI]: 78%-100%) with eltrombopag versus 67.5% (95% CI: 57%-78%) for controls. Number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and non-relapse mortality were similar between groups.
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Single-agent lenalidomide maintenance after upfront autologous stem cell transplant for newly diagnosed multiple myeloma: The MD Anderson experience
Pasvolsky, O., Milton, D. R., Masood, A., Sami, S. S., Tanner, M. R., Bashir, Q., Srour, S., Saini, N., Lin, P., Ramdial, J., et al
American journal of hematology. 2023
Abstract
The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single-center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single-agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4-82.3) years, and high-risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03-139.6) months. After a median follow-up of 47.9 (range 2.9-171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2-61.4) months and 111.3 (95% CI 101.7-121.5) months, respectively. In MVA, high-risk cytogenetics was associated with a worse PFS (HR 1.91) and OS (HR 1.73) (p < .001 for both). Use of KRD induction and achievement of MRD-negative ≥ VGPR before autoHCT were associated with an improved PFS (HR 0.53 and HR 0.57, respectively; p < .001 for both). Longer maintenance duration, even with a 5-year cutoff, was associated with superior PFS and OS (HR 0.17 and 0.12, respectively; p < .001 for both). A total of 106 patients (9%) developed a second primary malignancy (SPM), mostly solid tumors (39%) and myeloid malignancies (30%). Longer maintenance duration was associated with a higher risk of SPM, reaching statistical significance after >2 years (odds ratio 2.25; p < .001). In conclusion, outcomes with Len maintenance were comparable to those reported in large clinical trials. Longer duration of maintenance, even beyond 5 years, was associated with improved survival.
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3.
Lenalidomide-Based Maintenance After Autologous Hematopoietic Stem Cell Transplant for Patients with High-Risk Multiple Myeloma
Pasvolsky, O., Milton, D. R., Rauf, M., Tanner, M. R., Bashir, Q., Srour, S., Tang, G., Saini, N., Ramdial, J., Masood, A., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Maintenance therapy with single-agent lenalidomide (Len) after autologous hematopoietic stem cell transplantation (autoHCT) for multiple myeloma (MM) is associated with improved progression-free survival (PFS). However, MM patients with high-risk chromosomal abnormalities (HRMM) may need a more intense regimen. OBJECTIVE We hypothesized that adding another anti-myeloma drug to Len maintenance would lead to improved outcomes. STUDY DESIGN We conducted a retrospective single-center chart review analysis of adult HRMM patients who received autoHCT between 2008-2018, followed by Len-based maintenance therapy. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization (FISH). We divided patients into those who received either single-agent Len maintenance (Len-only) or Len-based combinations (Len-combo). We compared non-relapse mortality (NRM), day 100 and best post-transplant responses, minimal residual disease (MRD) status, PFS, and overall survival (OS) between the two groups. We also performed sensitivity analyses using inverse probability weights to correct for potential bias due to nonrandomization of the two groups. RESULTS A total of 231 patients with HRMM were included in our analysis, with a median age of 62.4 (range 33.5-79.9) years, and 55% were male. There were 153 patients in the Len-only group and 78 in the Len-combo group. Len-combo regimens were either doublets (Len with dexamethasone [dex: n=10], elotuzumab [n=28] or ixazomib [n=14]) or triplets (Len with bortezomib/dex [n=10], ixazomib/dex [n=10] or carfilzomib/dex [n=6]). More patients in the Len-combo group had ≥2 high-risk cytogenetic abnormalities compared to the Len-only group (32% vs. 12%: p<0.001). Median follow-up was 40.7 and 37.0 months in the Len-only and Len-combo groups, respectively. Median PFS and OS for all patients were 25.5 and 82.6 months, respectively. There was no significant difference in PFS (hazard ratio [95% CI]: 1.01 [0.71-1.44], p=0.94) or OS (0.84 [0.49-1.43], p=0.52) between the Len-only and the Len-combo groups, respectively. However, for patients with high-risk cytogenetic abnormalities other than 1q+, there was a trend towards better PFS in the Len-combo group (0.59 [0.32-1.09], p=0.09), but no difference in OS (0.79 [0.37-1.65], p=0.53). CONCLUSIONS In this single center retrospective analysis, use of Len-based combinations for post-transplant maintenance did not show improvements in HRMM patient outcomes. However, there was a trend towards improved PFS in patients with high-risk abnormalities other than 1q+.
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Eltrombopag for Post-Transplantation Thrombocytopenia: Results of Phase II Randomized, Double-Blind, Placebo-Controlled Trial
Ahmed, S., Bashir, Q., Bassett, R., Poon, M. C., Valdez, B., Konoplev, S., Alousi, A. M., Andersson, B. S., Ciurea, S., Hosing, C., et al
Transplantation and cellular therapy. 2021;27(5):430.e1-430.e7
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Free full text
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Editor's Choice
Abstract
Prolonged thrombocytopenia occurs in up to 37% of patients after hematopoietic stem cell transplantation (HSCT) and is associated with adverse prognosis and increased risk of bleeding. Eltrombopag, a thrombopoietin receptor agonist, can increase platelet counts in thrombocytopenic patients. We conducted a phase II study, adaptively randomizing patients at =35 days post-HSCT to receive placebo or eltrombopag at a platelet count =20,000/µL for 7 days or platelet transfusion-dependent and a neutrophil count =1500/µL. Sixty patients were randomized to eltrombopag (n = 42) or placebo (n = 18) and received at least 1 dose. Fifteen patients (36%) in the eltrombopag arm achieved a platelet count of =30,000/µL, compared with 5 patients (28%) in the placebo arm, with a posterior probability of 0.75. (The protocol required this probability to be >0.975 to declare a winner; thus, the results are inconclusive.) However, 9 patients (21%) in the eltrombopag arm achieved a platelet count of =50,000/µL, compared with no patients in the placebo arm (P = .046). The overall survival, progression-free survival, relapse rate, and nonrelapse mortality were similar in the 2 arms. In conclusion, compared with placebo, treatment with eltrombopag led to a higher percentage of patients achieving a platelet count of =50,000/µL in patients with persistent thrombocytopenia after HSCT.
PICO Summary
Population
Patients with a platelet count =20,000/µL for 7 days or platelet transfusion-dependent and a neutrophil count =1500/µL (n=60)
Intervention
Eltrombopag (n=42)
Comparison
Placebo (n=18)
Outcome
Fifteen patients (36%) in the eltrombopag arm achieved a platelet count of =30,000/µL, compared with 5 patients (28%) in the placebo arm, with a posterior probability of 0.75. 9 patients (21%) in the eltrombopag arm achieved a platelet count of =50,000/µL, compared with no patients in the placebo arm. The overall survival, progression-free survival, relapse rate, and nonrelapse mortality were similar in the 2 arms.
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Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation for B-lineage Acute Lymphoblastic Leukemia
Gaballa, M. R., Banerjee, P. P., Milton, D. R., Jiang, X., Ganesh, C., Khazal, S. J., Nandivada, V., Islam, S., Kaplan, M., Daher, M., et al
Blood. 2021
Abstract
Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single center phase II study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least one cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44-105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute GVHD grades 2-4 and 3-4 were 33% and 5%, respectively; two cases of mild (10%) and one case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival, progression-free survival, and non-relapse mortality rates were 85%, 71%, and 0%, respectively. In a matched-analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and post-treatment samples identified patients with specific T-cell profiles as "responders" or "non-responders" to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Non-responders were T-cell deficient and expressed more inhibitory checkpoint molecules, including TIM3. We found that blinatumomab post-allogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment.
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Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma
Mian, I., Milton, D. R., Shah, N., Nieto, Y., Popat, U. R., Kebriaei, P., Parmar, S., Oran, B., Shah, J. J., Manasanch, E. E., et al
Cancer. 2016;122(24):3831-3837
Abstract
BACKGROUND Although lenalidomide maintenance therapy has demonstrated improved outcomes after autologous hematopoietic stem cell transplantation (auto-HCT) for patients with multiple myeloma (MM), the impact of the duration of this therapy is not clearly known. METHODS This study retrospectively analyzed all MM patients who were placed on maintenance lenalidomide after auto-HCT between January 2007 and December 2013. Progression-free survival (PFS) and overall survival (OS) were analyzed in multivariate Cox proportional hazards regression models that included the duration of maintenance as a time-dependent covariate. RESULTS Of the 464 patients identified, 46% initiated therapy early (<4 months after auto-HCT). The median PFS and OS were 38 and 78 months, respectively. Improvements in PFS (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04-0.38; P<.001) and OS (HR, 0.09; 95% CI, 0.03-0.26; P<.001) were seen for those on maintenance for >2 years versus those on maintenance for <2 years. For those on maintenance for >3 versus those on maintenance for <3 years, this trend continued with improvements seen in PFS (HR, 0.02; 95% CI, 0.00-0.44; P=.012) and OS (HR, 0.05; 95% CI, 0.00-0.83; P=.037). The incidence of second primary malignancies (SPMs) in the entire cohort was 3%. No differences were seen in survival between early and late initiators of maintenance lenalidomide. CONCLUSIONS A longer duration of maintenance therapy was associated with longer survival. The incidence of SPMs was low, and they were not associated with the duration of maintenance. The timing of the initiation of maintenance had no effect on survival. Cancer 2016;122:3831-3837. © 2016 American Cancer Society. Copyright © 2016 American Cancer Society.