scholarly journals Improving outcomes after allogeneic hematopoietic cell transplantation for Hodgkin lymphoma in the brentuximab vedotin era

2017 ◽  
Vol 52 (5) ◽  
pp. 697-703 ◽  
Author(s):  
L Hegerova ◽  
Q Cao ◽  
A Lazaryan ◽  
B L McClune ◽  
D J Weisdorf ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Brentuximab Vedotin ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation

Brentuximab Vedotin (SGN-35) Enables Successful Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 664-664 ◽  
Author(s):  
Robert W. Chen ◽  
Stephen J. Forman ◽  
Joycelynne Palmer ◽  
Ni-Chun Tsai ◽  
Leslie Popplewell ◽  
...  
Keyword(s):  
Disease Control ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Infectious Complications ◽  
Brentuximab Vedotin ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Antibody Drug Conjugate

Abstract Abstract 664 Background: The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by a lack of disease control prior to transplantation. Brentuximab vedotin (b-vedotin, SGN-35), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Chen 2011). To examine the impact of b-vedotin on RIC allo-HCT, we performed a retrospective analysis of relapsed/refractory HL patients who received b-vedotin at City of Hope National Medical Center (COH) and Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) and then went on to receive RIC allo-HCT. Methods: Between October 2008 and July 2011, 46 patients with relapsed/refractory HL received b-vedotin at COH and SCCA through Seattle Genetics trials (SGN-35-03, 06, 07, and 08). 16/46 (34.8%) patients subsequently underwent RIC allo-HCT, including 12 at COH (2/12 were transplanted at University of Utah and Wellington Hospital) and 4 at the SCCA. The baseline characteristics are listed in Table 1. All 12 COH patients received fludarabine/melphalan as the conditioning regimen, 5/12 used matched related donors and 7/12 used matched unrelated donors. 10/12 received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis and 2 patients received mycophenolate mofetil (MMF) and cyclosporine (CSP). In contrast, 3/4 patients transplanted at the SCCA received haploidentical donors transplantation using fludarabine/cytoxan/2Gy TBI conditioning and cytoxan/tacrolimus/MMF as GVHD prophylaxis while 1/4 underwent conditioning using 2Gy TBI followed by CSP/MMF prophylaxis. Patients were monitored for engraftment, aGVHD, cGVHD, chimerism, and infectious complications per institutional standards. Each institutional review board approved the retrospective analysis of individual center data and we plan to present combined analysis of COH/SCCA data at ASH. Results: At COH, the 1 year PFS was 90% (95% CI: 54.0, 98.2) and the 1 year OS was 100% with a median follow-up of 13.2 months (range: 2, 20), In addition, the 1 year relapse rate was 10% (95% CI: 1.7, 46) and the non-relapse mortality at 1 year was 0%. Likewise, all 4 of the SCCA patients are alive and progression-free with a median follow up of 7.2 months (range: 2.9, 19). For the entire cohort the rates of aGVHD and cGVHD were 25% and 63%, respectively. There was no grade III-IV aGVHD and only 1/16 (6.3%) with extensive cGVHD. There was no delay of engraftment or increased incidence of CMV/EBV infections (Table 1). The only patient who relapsed after RIC allo-HCT had progressive disease at the time of transplantation, and 276 days had elapsed between the last dose of b-vedotin to RIC allo-HCT. Conclusion: These data suggest that b-vedotin prior to RIC allo-HCT in HL can yield prolonged disease control without a delay in engraftment, increase in non-relapse mortality, aGVHD, cGVHD, and post transplant infectious complications. Such a strategy may allow more patients with relapsed or refractory HL to gain sufficient pre-transplant disease control to undergo this potentially curative procedure. Disclosures: Chen: Seattle Genetics: Consultancy, Research Funding. Off Label Use: SGN-35, a novel antibody drug conjugate, is used as salvage therapy for relapsed hodgkin lymphoma prior to allogeneic hematopoietic cell transplantation. Grove:seattle genetics: Employment. Gopal:Bio Marin: Research Funding; SBio: Research Funding; Pfizer: Research Funding; Abbott: Research Funding; Millenium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Piramal: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Spectrum: Research Funding; GSK: Research Funding; Biogen-Idec: Research Funding.

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

Brentuximab Vedotin Improves HCT-CI, CR Status, and Peri-Transplant Toxicity In Patients With Relapsed/Refractory Hodgkin Lymphoma Heading To RIC Allo-HCT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3374-3374 ◽  
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Ni-Chun Tsai ◽  
Sandra H. Thomas ◽  
Tanya Paris ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Objective Response ◽  
Case Series ◽  
Brentuximab Vedotin ◽  
Hematopoietic Cell ◽  
Consecutive Case ◽  
Antibody Drug Conjugate ◽  
Co Morbidity

Abstract Background The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by patient co-morbidities, lack of disease control prior to HCT, and transplant related morbidities/mortalities. Brentuximab vedotin (BV), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Younes 2012). We performed a retrospective analysis comparing patient characteristics prior to HCT and outcomes after HCT in relapsed/refractory HL patients who received BV and underwent RIC allo-HCT versus those who did not receive BV but underwent RIC allo-HCT. Methods Between Jan 2003 and July 2009 (Pre-BV era), we identified a consecutive case-series of 23 HL patients who underwent RIC allo-HCT with no prior BV exposure (no-BV group). From July 2009 to Dec 2012, we identified a consecutive case-series of 21 additional HL patients who received BV prior to RIC allo-HCT (BV group). Co-morbidities at the time of HCT were measured by the HCT-CI. The Bearman scale was used to capture toxicities associated with RIC allo-HCT. PFS and OS were calculated using Kaplan-Meier method. Results Baseline characteristics are listed in Table 1. All patients received fludarabine and melphalan conditioning regimens. Groups were similar in terms of age, stage, response to induction, number of prior therapies, donor type, cell source, and prior auto-HCT. Groups differed in terms of GVHD prophylaxis (institutional shift to tacro/siro from 2005), remission status, and co-morbidity index (HCT-CI) at the time of HCT. Patients in the BV group were more likely to be in complete remission (CR) at the time of transplant (p=0.04). The median HCT-CI was better in the BV group (0 vs. 2, p=0.003). Also the Bearman toxicity score during transplant showed fewer grade III-IV events in the BV patients (0 vs. 7, p=0.015). The median follow-up for living patients in the no-BV group was 70.2 month and 23.3 months for the BV group (5 year lag for BV group). The 2-yr PFS for the no-BV group was 26.1% (95% CI: 21.5, 30.9) compared to 51.8% (95% CI: 38.5, 63.6) for the BV group, p=0.099. The 2-yr cumulative incidence of relapse/progression for no-BV was 56.5% (95% CI: 33.2, 74.4) compared to 28.9% (95% CI: 9.9, 51.4) for BV, p= 0.066. The 2-yr OS was 56.5% (95% CI: 44.3, 67) for no-BV compared to 66.6% (95% CI: 47.8, 80.0) for BV. Non-relapse mortality (NRM) at day 100 was 4.3% and 17.4% at 1 yr for the no-BV group. For the BV group NRM at day 100 was 0% and 11.8% at 1 yr. The rate of aGVHD and cGVHD were 56.5% and 78.3% for no-BV, and 33.3% and 76.2% for BV groups, respectively. Conclusion BV prior to RIC allo-HCT in relapsed HL leads to improvements in 1) HCT-CI 2) CR status at time of transplant, and 3) reduced peri-transplant toxicity. Disclosures: Chen: Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Trave expenses Other. Siddiqi:Seattle Genetics: Speakers Bureau.

scholarly journals Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2744-2748 ◽  
Author(s):  
Christoph Kahl ◽  
Barry E. Storer ◽  
Brenda M. Sandmaier ◽  
Marco Mielcarek ◽  
Michael B. Maris ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Low Grade ◽  
High Grade ◽  
Lymphoid Malignancies ◽  
Relapse Rates

Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

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