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Efficacy of Proteasome Inhibitor-Based Maintenance following Autologous Transplantation in Multiple Myeloma: a systematic review and meta-analysis
Parrondo, R. D., Reljic, T., Iqbal, M., Ayala, E., Kharfan-Dabaja, M. A., Kumar, A., Murthy, H. S.
European journal of haematology. 2020
Abstract
INTRODUCTION Lenalidomide maintenance, commonly prescribed in the post-autologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta-analysis to assess the efficacy of PIM in MM. METHODS Performing a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion. RESULTS A total of 1,760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n=261) or thalidomide (n=358). PIM did not improve OS (HR 0.88, 95% CI 0.73-1.05, p=0.15) but improved PFS (HR 0.77, 95% CI 0.69-0.86, p= <0.00001) and DOHR (HR 0.88, 95% CI 0.79-0.98, p=0.02) compared to control. There were no significant differences between PIM and control regarding SPM (p=NS) and =grade 3 peripheral neuropathy (PN) (p=NS). CONCLUSIONS PIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared to placebo/thalidomide.
2.
Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT
Kanate, A. S., Kumar, A., Dreger, P., Dreyling, M., Le Gouill, S., Corradini, P., Bredeson, C., Fenske, T. S., Smith, S. M., Sureda, A., et al
JAMA oncology. 2019
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Abstract
Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naive high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naive FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.
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Maintenance tyrosine kinase inhibitors following allo-HCT for chronic myeloid leukemia: A CIBMTR Study
DeFilipp, Z., Ancheta, R., Liu, Y., Hu, Z. H., Gale, R. P., Snyder, D., Schouten, H. C., Kalaycio, M., Hildebrandt, G. C., Ustun, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myeloid leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML transplanted from 2007-2014 who received maintenance TKI following HCT (n=89) as compared to no TKI maintenance (n=301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy prior to HCT. The majority of patients had disease beyond CP1 at HCT (n=240, 62%). The study was conducted as a landmark analysis, excluding patients that died, relapsed, had chronic graft-versus-host disease or were censored prior to Day 100 following HCT. Of the 89 patients receiving TKI maintenance, 77 (87%) received a single TKI while 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n=50), imatinib (n=27) and nilotinib (n=27). As measured from Day 100, the adjusted estimates for 5-year relapse (maintenance, 35% vs. no maintenance, 26%; p=0.11), leukemia-free survival (LFS, maintenance, 42% vs. no maintenance, 44%; p=0.65) or overall survival (OS, maintenance, 61% vs. no maintenance, 57%; p=0.61) did not significantly differ between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by the status of disease prior to transplant. In conclusion, our data did not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes in a Day 100 landmark analysis. The optimal approach to TKI administration in the post-transplant setting in CML remains undetermined.
PICO Summary
Population
Adult patients with CML transplanted from 2007-2014 (n=390)
Intervention
Maintenance TKI following HCT (n=89)
Comparison
no TKI maintenance (n=301)
Outcome
As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; ) or overall survival (maintenance, 61% versus no maintenance, 57%; ) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation.