0
selected
-
1.
Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma
Moskowitz, A. J., Shah, G., Schöder, H., Ganesan, N., Drill, E., Hancock, H., Davey, T., Perez, L., Ryu, S., Sohail, S., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;39(28):3109-3117
-
-
Free full text
-
Abstract
PURPOSE We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550). METHODS Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m(2) IV, days 1 and 8), vinorelbine (20 mg/m(2) IV, days 1 and 8), and liposomal doxorubicin (15 mg/m(2), days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.
-
2.
Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD
Arnold, D. E., Nofal, R., Wakefield, C., Lehmberg, K., Wustrau, K., Albert, M. H., Morris, E. C., Heimall, J. R., Bunin, N. J., Kumar, A., et al
Journal of clinical immunology. 2021;:1-10
Abstract
X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n?=?30, 75%) and HLA-mismatched (n?=?10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p?=?0.01) and 8.2 (CI 2.1-32.7, p?0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT.
-
3.
Reduced intensity is preferred over myeloablative conditioning allogeneic HCT in chronic lymphocytic leukemia whenever indicated: A systematic review/meta-analysis
Kharfan-Dabaja, M. A., Moukalled, N., Reljic, T., El-Asmar, J., Kumar, A.
Hematology/Oncology & Stem Cell Therapy. 2017
Abstract
Despite availability of new and more effective therapies for chronic lymphocytic leukemia, presently this disease remains incurable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Recent published clinical practice recommendations on behalf of the American Society for Blood and Marrow Transplantation relegated the role of for allogeneic hematopoietic cell transplantation to later stages of the disease. To our knowledge, no randomized controlled trial has been performed to date comparing myeloablative versus reduced intensity conditioning regimens in chronic lymphocytic leukemia patients eligible for the procedure. We performed a systematic review/meta-analysis to assess the efficacy of allogeneic hematopoietic cell transplantation when using myeloablative or reduced intensity conditioning regimens. We report the results in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Based on lower non-relapse mortality and slightly better overall survival rates, reduced intensity conditioning regimens appear to be the most desirable choice whenever the procedure is indicated for this disease. It appears highly unlikely that a RCT will be ever performed comparing reduced intensity vs. myeloablative allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia. In the absence of such a study, results of this systematic review/meta-analysis represent the best available evidence supporting this recommendation whenever indicated in patients with chronic lymphocytic leukemia.
-
4.
Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Gray Zone Lymphoma: a US Multicenter Collaborative Study
Kharfan-Dabaja, M. A., Raj, R., Nikolaenko, L., Ahmed, S., Reddy, N., Nathan, S., Cherry, M., El-Jurdi, N., Obiozor, C., Fenske, T. S., et al
Biology of Blood & Marrow Transplantation. 2017
Abstract
High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) has been anecdotally prescribed in gray zone lymphoma (GZL), showing encouraging efficacy. We conducted a multicenter retrospective study aimed to assess outcomes after auto-HCT in 32 patients with GZL treated at 9 transplant centers in the United States. Median age of patients at transplantation was 38 (18-70) years and the majority were male (n=21, 66%). Median number of lines of therapy prior to transplantation was 2 (1-4). BEAM was the most commonly prescribed regimen (n=23, 72%). Median follow up for surviving patients was 34 (1-106) months. Median OS was not reached. The 3-year PFS and OS for all patients were 69% and 78%, respectively. Three-year PFS and OS was 100% for patients who received only 1 line of therapy prior to auto-HCT vs. 65% (PFS, p=0.25) and 75% (OS, p=0.39) for those receiving >1 line. Cumulative incidence of relapse/progression at 1-year and 3-year post-transplantation were 4% and 31%, respectively. The 3-year NRM was 0. These findings suggest that HDT and auto-HCT is an effective treatment in patients with GZL. Our findings would ideally require confirmation in a larger cohort of patients, preferably in the setting of large prospective multicenter RCTs. However, we acknowledge that such studies could be hard and improbable to conduct in GZL owing to its rarity. Alternatively, a multicenter prospective study, which includes tissue banking and a data registry, to help better understand the biology and natural history of the disease is warranted.
-
5.
Reduced-intensity or myeloablative allogeneic hematopoietic cell transplantation for mantle cell lymphoma: a systematic review. [Review]
Kharfan-Dabaja, M. A., Reljic, T., El-Asmar, J., Nishihori, T., Ayala, E., Hamadani, M., Kumar, A.
Future Oncology. 2016;12(22):2631-2642
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is the only known treatment that can offer a cure in mantle cell lymphoma, but it is unclear if regimen dose-intensity offers any advantage. We performed a systematic review/meta-analysis to assess efficacy of allo-HCT using myeloablative or reduced-intensity conditioning. We report results according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. On the basis of a relatively lower nonrelapse mortality and a slightly better progression-free survival/event-free survival and overall survival rates, reduced-intensity allo-HCT regimens appear to be the preferred choice when an allo-HCT is being considered for mantle cell lymphoma. The higher rate of relapse when offering reduced-intensity regimens cannot be ignored but certainly highlights opportunities to incorporate post-transplant strategies to mitigate this risk. A prospective comparative study is ultimately needed to generate more conclusive evidence.