Bendamustine, Etoposide, Cytarabine and Melphalan (BeEAM) Followed By Autologous Stem Cell Transplantation Produce a 3-Year Progression-Free Survival Of 75% In Heavily Pre-Treated Hodgkin and Non-Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2134-2134
Author(s):  
Giuseppe Visani ◽  
Pietro Maria Stefani ◽  
Saveria Capria ◽  
Lara Malerba ◽  
Piero Galieni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Disease Type ◽  
Cell Transplant ◽  
Free Survival ◽  
End Point

Abstract Background We previously demonstrated (Visani et al, Blood 2011) the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to autologous stem cell transplant (ASCT) in resistant/relapsed lymphoma patients (EUDRACTnumber2008-002736-15). Furthermore, this regimen showed significant anti-lymphoma activity (80% CR). At the time of publication (2011), disease type (NHL versus HL) and disease status at transplant (chemosensitive versus chemoresistant) were the only statistically significant variables influencing PFS (p=0.01; p=0.007). However, median follow-up for surviving patients was short (18 months), therefore, it was not possible to draw final conclusions on the efficacy. Aims We evaluated the efficacy of the BeEAM regimen in terms of disease-free (DFS) and overall survival (OS) after a median follow-up of 41 months. Methods Forty-three patients (median age 47 years, range 18-70) with resistant/relapsed NHL (28) or Hodgkin lymphoma (HL, 15) were consecutively enrolled in the study. Twenty-one patients had primary refractory disease, whereas 22 had relapsed disease, 5 of whom where in second or subsequent relapse, at the time of enrolment. The study was designed according to Fleming’s method. The primary objective of the study was to determine the 36-months event free survival rate. We fixed the lowest acceptable rate as 40% and the successful rate as 60%, with a significance level a=0.05 and a power 1-b =0.80. At the time of publication, the median follow-up was 18 months, and therefore it was not possible to establish if we had met the primary end-point of the study. Results we updated the follow-up at 41 months after transplant. Thirty-one out of 43 patients are still in CR (72%), as documented by both PET and CT scan. Two patients with HL were refractory and rapidly died, whereas 10/43 patients (23%) relapsed after a median time of 7.5 months (range:3-23) from transplant. Five patients died (3 NHL, 2 HL), whereas 5 patients are still alive after relapse. Median PFS and OS were still not reached. Conversely, 3-year PFS was 75%, allowing our study to met its primary end-point. Interestingly, disease type (HL versus NHL) at transplant is no longer influencing PFS (p=0.7), and still does not influence OS (p=0.1). On the other hand, disease status at transplant (chemosensitive vs chemoresistant) is still a strong predictor of both PFS and OS (p=0.03 and p=0.009, respectively). At present, one patient developed myelodisplasia after transplant. No other late effects were observed up to now. Conclusions The new BeEAM regimen met the primary end-point of the study and confirms its safety, after 41 months of follow-up. Interestingly, NHL and HL were not statistically different in terms of both PFS and OS at 41 months of observation. These data confirm the high efficacy of this regimen in heavily pretreated non-Hodgkin, as well as Hodgkin lymphoma. Acknowledgments supported in part by AIL Pesaro Onlus. Disclosures: Ocio: Onyx: Consultancy, Research Funding; Novartis: Consultancy; Array Biopharma: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding.

scholarly journals Outcome of Hodgkin Lymphoma after Progression Following Autologous Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2994-2994
Author(s):  
Joseph M. Connors ◽  
Alina S Gerrie ◽  
Maryse M Power ◽  
Kerry J Savage
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Single Agent ◽  
Progression Free Survival ◽  
Brentuximab Vedotin ◽  
Primary Objective ◽  
Initial Diagnosis ◽  
Cell Transplant ◽  
Free Survival

Abstract Background Clinical trials have demonstrated a high level of effectiveness for brentuximab vedotin (BV) for patients with relapsed or refractory classical Hodgkin lymphoma (HL); however, how patients fare in routine clinical practice if their HL recurs after autologous stem cell transplant (ASCT) is less clear. Our primary objective was to characterize overall survival (OS) and progression-free survival (PFS) among a cohort of real-world patients treated with BV after ASCT. The secondary objective was to characterize the outcome of treatment after failure of ASCT or ASCT and BV. Methods We screened the population-based British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database to identify patients with classical HL (excluding lymphocyte predominant HL) who were aged >16 years at initial diagnosis, staged and treated in BC, had primary treatment with ABVD or equivalent chemotherapy, underwent ASCT as part of first treatment for refractory or relapsed disease and relapsed again after ASCT. We excluded patients who have been treated at any time with a checkpoint inhibitor. We determined Kaplan-Meier estimates of overall (OS) and progression free survival (PFS) from the date of the progression that occurred after ASCT and, for those treated with the agent, after subsequent BV. Therapies given in sequence without a pause between therapies were considered part of the same line of therapy. Results Between 1986 and 2015 93 patients experienced recurrence of HL after ASCT. Their median age at initial diagnosis was 30 years and 51% were male. After failure of ASCT 23 (25%) received radiation monotherapy and 61 received chemotherapy (66%), either as a single agent or in various combinations and of these 9 (10%) also received radiation; 6 (6%) received a second transplant (5 allogeneic and 1 repeat ASCT); and 5 refused or were too frail for treatment other than with corticosteroids. The median PFS and OS from the time of relapse after ASCT for these 93 patients were 7.1 (range 0.2-352) and 16.2 months (range 0.2-352), respectively. Of those 93, 17 patients received BV alone or BV+bendamustine at some point following ASCT. The median age of BV-treated patients was 33 years at the time of their original diagnosis and 29% were male. Among those 17 patients, 9 received single agent BV and 8, BV+bendamustine as part of a clinical trial. The median time from ASCT to the start of BV was 27.5 months. Counting ASCT as 2nd line treatment, 10 individuals received BV as 3rd line, 6 as 4th line and 1 as 5th line therapy. For all 17 patients the subsequent median PFS and OS from the time of BV initiation were 5.1 (range 1.5-34.6) and 18.8 months (range 2.4-40.5), respectively. 12 of these patients relapsed again and their subsequent median PFS and OS were 0.6 (range 0.5-29) and 3 (range 0.5-30) months, respectively. All 9 patients who received single agent BV relapsed again at a median of 2 months (range 1.2-9.7); 5 of the 8 patients treated with BV+bendamustine remain in remission 6 to 36 months later. Conclusions These data highlight the poor prognosis for patients with relapsed or refractory cHL, particularly for those whose lymphoma recurs after brentuximab vedotin as well as the highly individualized management of patients whose lymphoma has recurred after ASCT. Future therapies that prevent or significantly delay relapse will help in alleviate the substantial clinical burden due to relapsed and refractory Hodgkin lymphoma. Disclosures Connors: Millennium Takeda: Research Funding; Seattle Genetics: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding.

Analysis of Beam (Carmustine, Etoposide, Cytosine Arabinoside, Melphalan) Versus High Dose Melphalan (HDM) with Autologous Rescue in Multiple Myeloma(MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5227-5227 ◽  
Author(s):  
Karthikeyan A. Ramasamy ◽  
Ruth Branford ◽  
Radha Selvaratnam ◽  
Aloysius Y.L. Ho ◽  
Rafael Duarte ◽  
...  
Keyword(s):  
Stem Cell ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Significant Prolongation ◽  
Disease Free

Abstract Autologous stem cell transplantation is an established treatment that leads to prolongation in overall and disease free survival in MM. BEAM and M have been widely used as conditioning regimen for autologous stem cell transplant (ASCT) in patients with MM. At our centre MM patients with low creatinine clearance (Crcl) and a low performance status were offered Melphalan only as conditioning regime for ASCT. We report on our experience of HDM in comparison with standard BEAM. Records of 53 consecutive patients who had ASCT for myeloma at our centre between 2000 and 2003 were examined. Patients were staged as per Salmon and Durie (SD) criteria and EBMT response criteria were used for assessment post transplant .35 patients had BEAM conditioning (SD criteria 31-IIIA, 3-IA, 1-IIA) and 18(SD criteria 14- IIIA, 4-IIIB) had M.).Patients who received BEAM had a median age of 55 (range 38–66), median follow up of 19 months and those who received HDM had a median age of 60 (range 45 –69), follow up of 20.5 months. Stem cell source was peripheral blood (PBSC) in 50 patients, 1 Bone marrow (BM), and 2 BM and PBSC. HDM at a Dosage of 140 –200 mg/m2was administered in all HDM cases except for 1 patient who had 70mg/m2 because of Crcl of 17.4 ml/min. BEAM group had Carmustine 300mg/m2 (−6), Ara- C 800mg/m2 (−5 to −2), Etoposide 800mg/m2 (−5 to −2), M 140mg/m2 (−1). Patients in the M group had significantly lower haemoglobin and higher serum creatinine levels in comparison with the BEAM group. The 100-day treatment related mortality (TRM) was 5.5 % in HDM group, which was comparable to 2.2 % in the BEAM group. 9 out of 18 patients who had HDM relapsed and 9 out of 35 patients who had BEAM relapsed at follow up with Median relapse free survival (RFS) being 575 days in HDM group and has not achieved yet in BEAM group (p= .017). This data confirm that BEAM ASCT lead to significant prolongation of disease free survival with low TRM.Our data also suggest the effectiveness of HDM in patients who because of poor performance status and/or abnormal renal function may not tolerate BEAM ASCT

Clinical Outcome of a Second Autologous Hematopoietic Stem Cell Transplant (HCT) for Non-Hodgkin (NHL) and Hodgkin Lymphoma (HL) Relapsing after a First Autotransplant.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3048-3048
Author(s):  
Sonali M. Smith ◽  
Koen van Besien ◽  
Jeanette Carreras ◽  
Julie M. Vose ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Disease Status ◽  
Large Cell ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Free Survival

Abstract Autologous HCT (autoHCT) salvages many patients (pts) with relapsed lymphomas but few relapsing after an autoHCT are cured. We determined feasibility of stem cell collection, engraftment kinetics, treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) for a second autoHCT (HCT2) for lymphoma relapsing after prior HCT (HCT1). We studied 35 pts, 20 with HL and 15 with diffuse or follicular large cell and immunoblastic NHL, receiving a HCT2 for relapse between 1986 and 2003 and reported to the CIBMTR. Median (range) age at HCT2 was 36 yrs (16–61); 61% had a performance score less than 90. HCT2 was performed >1 year after HCT1 in 80%. Median (range) time from diagnosis to HCT1 was 20 mo (4–162 mo), from HCT1 to relapse, 17 mo (3–68 mo), and from relapse to HCT2, 5 mo (1–40 mo). 83% underwent a 2nd stem cell / marrow harvest prior to HCT2. Median time to ANC >0.5 x 109/L was 11d. CBV or BEAM were the conditioning regimens for HCT1 in 80% and for HCT2 in 60%. The best response to HCT2 was complete remission in 22 pts and partial remission in 5; 8 pts had either no response or progressive disease. At a median follow up of 92 mo (32–124 mo) after HCT2, 26 pts (74%) have died with 17 (65%) dying of relapsed lymphoma. Two (6%) patients developed therapy-related MDS. The probability of TRM at day 100 was 12% (95% CI, 3–25%). The 1, 3 and 5 yr probability of PFS were 45% (95% CI, 29–62%), 33% (95% CI, 18–50%) and 30% (95% CI, 15–46%), respectively. The 1, 3 and 5 yr probability of OS were 63% (95% CI, 46–78%), 34% (95% CI, 19–50%) and 31% (95% CI, 17–47%), respectively. There were no differences in outcomes between HL or NHL. Pts relapsing >6mo after HCT1 appeared to have better OS (fig 1 and 2). In summary, HCT2 is feasible in pts with lymphoma after relapsing an HCT1. Stem cells harvested prior to HCT2 resulted in rapid engraftment with a day 100 TRM (12%) lower than that reported for alloHCT in this setting. Relapse is the primary reason for failure, but approximately one-third of pts enjoy long-term disease free survival. HCT2 should be considered for young pts with relapsed HL or NHL post-HCT1 without alternative transplant options. HCT1 (%) HCT2 (%) Sensitive disease status pre-HCT 26 (79) 24 (75) Stem cell source BM 15 (43) 10 (29) PBSC 13 (37) 21 (60) Both 7 (20) 4 (11) Median days to platelet recovery ≥ 20 x 109 /L 17 (7–376) 20 (1–101) Stem cell harvest between HCT1 and HCT2 29 (83) Different conditioning regimen for HCT2 25 (74) Outcomes TRM @ 1 yr 21 (9–37) PFS @ 5yrs 30 (15–46) OS @ 5 yrs 31 (17–47) Figure 1 Figure 1. Figure 2 Figure 2.

Prediction of Progression-Free Survival with Brentuximab Vedotin Therapy for Relapsed Hodgkin Lymphoma: A Retrospective Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3086-3086
Author(s):  
Anna Houk ◽  
Ajay K. Gopal ◽  
Edward N. Libby ◽  
Andrei R. Shustov ◽  
Damian J. Green ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Confidence Intervals ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Free Survival

Abstract Introduction: The role of brentuximab vedotin (BV) in Hodgkin Lymphoma (HL) is expanding, but factors predicting progression-free survival (PFS) after BV therapy are poorly defined. Age, tumor bulk, presence of extranodal disease, neutrophil:lymphocyte ratio (ANC/ALC), and lymphocyte:monocyte ratio (ALC/AMC) predict outcome in HL patients (pts) treated with chemotherapy, but their impact on PFS after BV has not been well-studied. Also, among pts with relapsed/refractory HL (rel/ref HL) who progress after BV, efficacy of additional chemotherapy is undefined. To inform patient selection and future clinical trial design with BV, we undertook a retrospective study to identify factors predicting PFS with BV therapy in rel/ref HL, and explore chemotherapy efficacy as salvage after BV failure. Methods: Pts receiving BV since 2009 were identified through pharmacy and research records and studied with IRB approval. Those with rel/ref HL receiving BV before or after transplant without intervening therapy were excluded. Age ≥40 at time, sex, pre-BV PET findings (SUV max, extranodal [EN] involvement, bulk > 5cm), prior therapy (# lines of therapy> median; prior transplant, platinum-containing, radiotherapy), and lab findings (AMC/ALC³4.3, ALC/AMC ratio³1) at time of start of BV were examined for an impact on PFS and OS via log-rank testing of Kaplan-meier projections(JMP 11.0 software). PFS was defined as time from first BV dose to radiographic or clinical progression, initiation of post-BV salvage, or death from any cause. OS was measured from date of first BV dose to death from any cause. Efficacy of salvage therapy for those failing BV was recorded. Results: Of 90 patient receiving BV, 43 met above criteria. Median age was 34 yrs (range 17-80), median # of pre-BV therapies was 3 (range 1-7). 31 (73%) had failed autologous transplant, 10 (23%) had undergone allogeneic transplant, and 20 (46%) received radiotherapy prior to BV. Pre-BV PET staging data was available in 26 pts; post-BV PET was not analyzed in this dataset as response criteria were nonstandardized. BV was administered for a median 6 cycles (range 2-20). Median PFS after BV was 6 mo. (Figure 1) with 4 pts having PFS >4 yrs. At 31 mo. median follow-up, 71% of pts were alive with no plateau in the survival curve. On univariate analysis, age 40 or older at time of BV predicted inferior PFS (p=.03) and inferior OS though 95% confidence intervals were wide (OS by age: Figure 2, p=.02). HR for death for pts age 40 or older was 4 (98% CI .03-2.3, p=.05). No other factor predicted PFS or OS. Among 29 pts who failed BV, OS was 3.4 yrs. 40 chemotherapy regimens were given with 11 responses. Five of 11 pts responded to bendamustine, but median time to progression was 4 mo. Two of 4 responded to gemcitabine as did 3/8 receiving platinum chemotherapy. Conclusions: In this cohort of rel/ref HL pts treated with BV, PFS was 6 mo. overall and inferior among pts 40 yrs or older. OS was also worse in this group, although confidence intervals were wide in both univariate analyses. We confirm and expand upon prior data showing features predicting outcomes in HL after chemotherapy do not clearly apply after BV; and that most pts progress <1 year after single-agent BV with a few durable remissions. Salvage chemotherapy after BV has transient efficacy. Larger studies defining clinical, biologic, and PET-based markers of outcome after BV are needed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Off Label Use: Brentuximab is approved in HL after failure of autologous stem cell transplant; in this series, some patients received Brentuximab before or when ineligible for an autologous stem cell transplant.. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Gilead: Research Funding; Spectrum: Research Funding; Teva: Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding.

scholarly journals Cord Blood Transplantation in Adolescents and Young Adults with Acute Leukemia: On Behalf of Eurocord, Ctiwp and PDWP of EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3369-3369
Author(s):  
Hiromi Hayashi ◽  
Fernanda Volt ◽  
Jaime Sanz ◽  
Eefke J. Petersen ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Advanced Disease ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Advisory Board ◽  
P Value ◽  
Free Survival ◽  
Disease Remission ◽  
Grade Ii

Abstract Outcomes for adolescents and young adults (AYA) might be considerably different from children and older adults with acute leukemia (AL). Patients in this transitory period tend to be considered at higher risk for poorer outcomes. However, AYA is still underrepresented in most hematopoietic stem cell transplant (HSCT) studies. Recent evidence shows superior outcomes for AYA with acute lymphoblastic leukemia (ALL) using pediatric rather than adult first line chemotherapy regimens. The aim of this study is to analyze outcomes of umbilical cord blood transplant (UCBT) in AYA patients with ALL or acute myeloid leukemia (AML) after myeloablative conditioning regimen (MAC). Eligibility criteria included patients with AL aged 15-25 (median 19) years, transplanted between 2004 and 2016 in EBMT centers, with single or double UCBT as first allogenic transplantation after MAC regimen and reported to Eurocord. A total of 504 patients were included. Primary endpoint was overall survival (OS). Median follow-up for survivors was 38 months (1 month-11 years). Median time from diagnosis to UCBT was 11 months (1 month-17 years) (interquartile range 5-29 months). Diagnosis was ALL in 59% (n=297) and AML in 41% (n=207); 64% of patients were male. Disease status at UCBT were 42% in 1st complete remission (CR) (n=203), 2nd CR in 38% (n=183), and advanced disease in 20% (n=96). Fifty eight percent of patients (n=293) received single and 42% (n=211) double UCBT. Cyclophosphamide + TBI ± fludarabine (45%) was the most frequently used conditioning regimen. Anti-thymoglobulin (ATG) was used in 54% and GVHD prophylaxis was cyclosporine A + mycophenolate mofetil in 44% of patients. Median nucleated cell dose at collection was 3.63 (range 0.9-9.0) X107/Kg for single and 5.25 (range 2.3-10.6) X107/Kg for double UCBT. The 3-year OS was 45±2%; 3-year leukemia free survival (LFS) was 41±2% and refined GVHD free/relapse free survival (rGRFS) was 32±2%. OS was similar in ALL and AML (45±3% vs 45±4%, p-value=0.69). According to disease status at UCBT, 3-year OS was 54±4% for patients in CR1, 48±4% for CR2 and 20±4% for advanced disease (p-value<0.001). Cumulative incidence function (CIF) for neutrophil engraftment at day-60 was 88% [95% confidential interval (CI) 85-90] in a median time of 24 days. CIF of acute GVHD grade II-IV at day-100 was 28% (95%CI 24-32) and out of the 233 patients with aGVHD, 73 (21%) had grade III-IV. The 1-year CIF of chronic GVHD was also 28% (95%CI 24-33) and out of the 124 patients with cGVHD, 52 (42%) had the extensive form. The 3-year CIF of transplant related mortality (TRM) was 31% (95%CI 24-33). The 3-year CIF of relapse was 28% (95%CI 24-32), and according to disease status at UCBT, relapse was 28% (95%CI 21-34) for patients in CR1, 24% (95%CI 18-31) for those in CR2 and 37% (95%CI 27-47) for advanced disease. Main causes of death were relapse (41%) and TRM (57%, mainly infections and GVHD). In multivariate analysis, disease remission at UCBT (HR 0.46, 95%CI 0.32-0.66, p-value<0.001) and transplant performed in more recent years (HR 0.75, 95%CI 0.62-0.90, p-value=0.002) were independently associated with increased OS. A similar effect was observed for LFS (recent transplantation: HR 0.80, 95%CI 0.66-0.95, p-value =0.01 and disease remission: HR 0.51, 95%CI 0.36-0.72, p-value <0.001). On the other hand, negative CMV serology (HR 0.77, 95%CI 0.61-0.99, p-value =0.042), recent transplantation (HR 0.85, 95%CI 0.73-0.99, p-value=0.49) and disease remission (HR 0.61, 95%CI 0.44-0.84, p-value =0.002) were significantly associated with increased rGRFS. For grade II-VI aGVHD, ATG use (HR 0.52, 95%CI 0.32-0.82, p-value=0.005), single UCBT (HR 0.63, 95%CI 0.42-0.96, p-value=0.03), and recent transplant (HR 0.76, 95%CI 0.59-0.98, p-value=0.034) reduced the risk. However, no factor was associated to cGVHD. This large series of AYA patients with AL provides detailed information on UCBT for this particular cohort with results comparable with other sources of HSCT. Due to the lack of information on pre-transplant chemotherapy (pediatric versus adult protocols), we were unable to evaluate its effect on outcomes. Nevertheless, this study contributes to a better understanding of HSCT for an age group that is not thoroughly described in most publications. Demonstrating the feasibility of UCBT in AYA patients is important to facilitate the decision of stem cell source selection when a more standard donor is not available. Disclosures Hough: University College London Hospital's NHS Foundation Trust: Employment. Angelucci:Vertex Pharmaceuticals Incorporated (MA) and CRISPR CAS9 Therapeutics AG (CH): Other: Chair DMC; Celgene: Honoraria, Other: Chair DMC; Jazz Pharmaceuticals Italy: Other: Local ( national) advisory board; Novartis: Honoraria, Other: Chair Steering Comiittee TELESTO Protocol; Roche Italy: Other: Local (national) advisory board. Bader:Medac: Patents & Royalties, Research Funding; Neovii: Research Funding; Riemser: Research Funding; Cellgene: Consultancy; Novartis: Consultancy, Speakers Bureau.

scholarly journals Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4018-4018
Author(s):  
Nikesh Dhiraj Chavda ◽  
Stephen Robinson ◽  
Ariane Boumendil ◽  
Irma Khvedelidze ◽  
Hervé Finel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Travel Grant

Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.

scholarly journals Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center

2021 ◽  
Vol 27 ◽  
Author(s):  
A. Kopińska ◽  
A. Koclęga ◽  
A. Wieczorkiewicz-Kabut ◽  
K. Woźniczka ◽  
D. Kata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Disease Status ◽  
Term Survival ◽  
Entire Cohort

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach.Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting.Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020.Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%.Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

scholarly journals Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1772-1772
Author(s):  
Santiago Pavlovsky ◽  
Astrid Pavlovsky ◽  
Isolda Fernandez ◽  
Miguel Pavlovsky ◽  
Virginia Prates ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Cell Transplant ◽  
Advanced Stage ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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