1.
Lenalidomide and dexamethasone with or without ixazomib maintenance tailored by residual disease status in myeloma
Rosiñol, L., Oriol, A., Ríos-Tamayo, R., Blanchard, M. J., Jarque, I., Bargay, J., Hernandez Garcia, M. T., Cabañas, V., Carrillo-Cruz, E., Sureda, A., et al
Blood. 2023
Abstract
From November 2014 to May 2017, 332 patients homogeneously treated with VRD induction, ASCT and VRD consolidation were randomized to receive maintenance therapy with RD (161 patients) vs IRD (171 patients). RD consisted of lenalidomide 15 mg/d from days 1-21 plus dexamethasone 20 mg/d on days 1-4 and 9-12 at 4-weeks intervals while in the IRD arm oral ixazomib at a dose of 4 mg on days 1,8, and 15 was added. MRD negative patients after 24 cycles were discontinued while those who were MRD positive remained on maintenance with RD for 36 more cycles. The MRD negativity from baseline increased from 50.9% to 71.8% with RD and from 59.6% to 72.4% with IRD at 2 years. After a median follow-up of 69 months from the initiation of maintenance, the PFS was similar in both arms, median not reached in either arm with a 6-years PFS rate of 61.3% and 55.6% for RD and IRD, respectively (HR 1.136 [95% CI 0.809 - 1.603]). No significant differences in PFS between RD and IRD were observed in any prognostic subgroup. After 2 years of maintenance, treatment was discontinued in 163 patients who were MRD negative while 63 MRD positive patients were continued on RD therapy. Maintenance discontinuation in MRD negative patients resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance discontinuation in MRD negative patients at 2 years. This trial is registered at ClinicalTrials.gov (NCT02406144) and EudraCT (2014-00055410).
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.
3.
Provisional Title: Safety Analysis of Brentuximab Vedotin From the Phase 3 AETHERA Trial in Hodgkin Lymphoma in the Posttransplant Consolidation Setting
Nademanee, A., Sureda, A., Stiff, P., Holowiecki, J., Abidi, M., Hunder, N. N., Pecsok, M., Uttarwar, M., Purevjal, I., Sweetenham, J.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The phase 3 AETHERA trial demonstrated brentuximab vedotin's (BV) efficacy as consolidation therapy in patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT; hazard ratio [HR]=0.57; P<0.001). The objective of this analysis is to provide further detail on the most common and clinically important treatment-emergent adverse events (TEAEs) in the AETHERA BV arm including their occurrence and management. AEs of clinical importance occurring in patients who participated in AETHERA (BV + best supportive care [BSC], n=165; placebo + BSC, n=164) were evaluated for time to onset, manageability through dose modification, and resolution. As previously reported, peripheral neuropathy (PN; 67%), infections (60%), and neutropenia (35%) were the most common BV-associated TEAEs. Neutropenia was managed with dose delays and granulocyte colony-stimulating factor; no dose reductions or discontinuations were required. The majority (57%) of PN cases were managed with dose delays and reductions. The median time to PN onset was 13.7 (range, 0.1-47.4) weeks. After end of treatment, PN continued to resolve; symptom resolution was similar to that in the placebo arm at 3 years, demonstrating reversibility. BV had no significant impact on preexisting PN. Patients with PN-related dose modifications had progression-free survival (PFS) comparable to patients without. Other less common but serious AEs, including pulmonary toxicities, hepatotoxicity, and cardiotoxicity, were rare in both arms and managed with BV dose modifications or discontinuations. Secondary malignancies were rare and reported in patients with comorbidities or other risk factors. Consolidation therapy with BV for patients with HL at high risk of relapse after auto-HSCT is associated with sustained PFS. The most common AEs in the BV arm were manageable and reversible. Awareness of these AEs and management approaches will enable healthcare providers and patients to plan the safest and most effective treatment plan.
4.
Panobinostat consolidation in patients with Hodgkin lymphoma at risk for relapse after high dose chemotherapy and autologous stem cell transplant: final results after early trial discontinuation
von Tresckow, B., Morschhauser, F., Szer, J., Eichenauer, D. A., Abramson, J. S., Sureda, A., Engert, A.
Leukemia & Lymphoma. 2017;58(1):222-225