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

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.

Download Full-text

Single UM171 Expanded Cord Blood Permits Transplantation of Better HLA Matched Cords with Excellent Gvhd Relapse Free Survival

Blood ◽

10.1182/blood-2018-99-110188 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4658-4658 ◽

Cited By ~ 2

Author(s):

Sandra Cohen ◽

Jean Roy ◽

Silvy Lachance ◽

Anne Marinier ◽

Jean-Sébastien Delisle ◽

...

Keyword(s):

Board Of Directors ◽

Culture System ◽

Research Funding ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Cell Dose ◽

Equity Ownership

Abstract Cord blood (CB) transplants have fallen into disfavor in large part due to low cell dose leading to prolonged hospitalizations and high transplant related mortality (TRM). UM171, a novel and potent agonist of hematopoietic stem cell (HSC) self-renewal could solve this major limitation, allowing for CB's important qualities of lower risk of chronic GVHD and relapse to prevail. In addition, UM171 could permit transplantation of smaller, better HLA matched cords, associated with lower TRM. Hence, we initiated a clinical trial to test the safety and efficacy of UM171 expanded CB (eCB). Our goal was to design a clinically viable eCB transplant with a TRM as low or lower than other HSC sources all the while maintaining CB's low relapse rate. Patients (pts) received a myeloablative conditioning regimen. On day (D)-7 of transplant, CB was thawed and CD34+ selected. The CD34- lymphocyte containing fraction was cryopreserved and infused on D+1. The CD34+ component was placed in a closed culture system with UM171 and media was injected once a day until D0, when cells were washed and infused. This fed-batch culture system allowed for small culture volumes, saving cost and labor. Between 7/16-6/18, 21 adult pts (median age 44 years) were transplanted with an eCB. Median final culture volume and net viable CD34 fold expansion were 670 mL and 35, respectively. Median 1st day of 100 and 500 neutrophils were D+10 and D+18, respectively. Achieving 100 neutrophils was 5 days faster than seen with our pts receiving peripheral blood (PB) or marrow (BM) and appeared cell dose independent, suggesting that clinically meaningful expansion of an early repopulating myeloid progenitor is at saturation even with smaller CBs. In contrast, attaining 500 neutrophils was accelerated but dependent on cell dose. More importantly, pts appeared to derive clinical benefit beyond neutrophil engraftment (defined as 500 neutrophils). Pts' median last day of fever prior to 500 neutrophils was D+8, much earlier than engraftment and 4 days earlier than seen with our PB-BM pts. We offer 2 hypotheses as explanation: i) 100 neutrophils, which are attained early, provide significant defense against infection, ii) the graft contains a significant proportion of dendritic cell precursors (30-40%) which offer mucosal protection during severe neutropenia. Duration of hospitalization was shorter by 12 days and longer by 2 days compared to our non eCB and PB-BM transplants, respectively. In addition, because cell dose requirements were lower, 12/21 pts received a better HLA matched CB, thus >80% of patients were transplanted with a ≥6/8 HLA matched eCB. As a result of lower minimal cell dose criteria, we can now use ∼half the CBs in the banks instead of only 5% for a 70 kg patient. Platelet engraftment occurred at a median of 42 days. With a median follow up of 14 months, there has been no CMV disease, no PTLD, 2 adenovirus cystitis, 2 (10%) grade 3-4 acute GVHD, no moderate/severe chronic GVHD and 1 TRM (5%) despite a median comorbidity index of 2 (0-5). Full donor chimerism was achieved in all cell subsets. Immune recovery was faster than seen in our unrelated donor transplants who routinely receive ATG prophylaxis with 196, 300 and 413 CD4+/µL at 3, 6 and 12 months, respectively. Interestingly, transcriptome analysis of UM171-eCB cells shows an enhanced lymphoid progenitor-associated gene signature when compared to DMSO exposed cells. Animals transplanted with UM171-eCB cells showed a 20 to 35-fold increase in thymic cellularity at 8 weeks post-transplant. Despite some very high risk pts in our trial, only 3 relapsed. Overall, progression free, and GVHD/relapse free survival (GRFS) are excellent at 95, 77 and 67%, respectively, at 12 months. A 7 day UM171 single eCB protocol is feasible and provides clinical benefits beyond faster engraftment with fewer infectious complications, better HLA matching and very low TRM, all the while saving production and hospitalization costs. Nevertheless, longer follow up will be required to better assess relapse howbeit encouraging preliminary results. Furthermore, patients' quality of life is paramount and best evaluated by GRFS which is excellent thanks to a very low rate of significant chronic GVHD all the while maintaining a low risk of relapse. In conclusion, this 1st trial documents the potency of UM171 and positions UM171-eCB as a promising HSC source which could compete with the current standard of care. Figure. Figure. Disclosures Cohen: ExCellThera: Patents & Royalties: Royalities from sales of UM171. Roy:ExCellThera: Patents & Royalties: Royalities from sales of UM171. Lachance:ExCellThera: Patents & Royalties: Royalities from sales of UM171. Roy:Hopital Maisonneuve Rosemont: Patents & Royalties: Author on patent; Kiadis Pharma: Other: Travel support; University of Montreal: Patents & Royalties: Author on patent. Busque:BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Paladin: Consultancy. Kiss:Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Caudrelier:ExCellThera: Employment. Zandstra:ExCellThera: Equity Ownership. Sauvageau:ExCellThera: Employment, Equity Ownership.

Download Full-text

Autologous Stem Cell Transplantation (ASCT) for Patients Aged 60 Years or Older with Classical Hodgkin Lymphoma : A Retrospective Analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Blood ◽

10.1182/blood.v124.21.1188.1188 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1188-1188

Author(s):

Aspasia Stamatoullas ◽

Pauline Brice ◽

Mor Seny Gueye ◽

Patrice Chevallier ◽

Reda Bouabdallah ◽

...

Keyword(s):

Heart Failure ◽

Bone Marrow ◽

Stem Cell ◽

Research Funding ◽

Median Number ◽

Salvage Chemotherapy ◽

Classical Hodgkin Lymphoma ◽

French Society ◽

Cell Therapies

Abstract Background: Twenty percent of classical Hodgkin Lymphoma (cHL) patients are aged 60 years or older. Their survival rate is inferior to that of younger patients for several reasons including lower delivery of standard chemotherapy and toxicity excess. For relapsed or refractory (R/R) cHL young patients, autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy. However, little is known regarding the outcome of R/R cHL in elderly patients (≥60 years) receiving ASCT. Method: The current report retrospectively analyzed the outcome of all consecutive patients aged 60 years or older with the diagnosis of R/R cHL who were transplanted between 1992 and 2013 and who were reported to the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) registry. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centers. This study was approved by the scientific committee of the SFGM-TC and is in accordance with Helsinki declaration for clinical research. Of note, specific study questionnaires were sent to transplant centers to obtain comprehensive, updated data. Results: One hundred and twenty patients met these criteria. Ninety-one patients (63M/28F) with documented data from 28 transplant centers were analyzed. Median age was 63 years at transplant (range 60-75). At diagnosis, 64 patients had advanced stage cHL, 46 had B symptoms and 6 had poor performance status (ECOG 2). Thirty-four patients had primary refractory disease, and 22 patients relapsed within the first year after first CR. The median number of salvage chemotherapy regimens was 2 (range 1-4). Most of the patients showed disease sensitivity to salvage treatment with 52 patients transplanted in CR, 5 patients in CRu, 30 patients in PR and 1 patient transplanted with progressive disease. The most frequently used conditioning regimen consisted of BEAM chemotherapy (93%) (Carmustine 300 mg/m2 d-6, Etoposide 100 mg/m2 Q12H d -5 to -2, Cytarabine 200 mg/m2 IV Q12H d-5 to -2, Melphalan 140 mg/m2 d -1). The median number of CD34 peripheral blood stem cells was 4.2 106 cells/kg (range 0.9-17.8). The median duration of hospitalization was 22 days (8-49). The median time to achieve neutrophil count >1x109/L and platelet count > 20x109/L were 11 days (range 8-104) and 13 days (range 7-115), respectively. Grade 3-4 toxicities occurred in 24 patients (mucositis: 13, sepsis: 3, interstitial pneumonia: 2, diarrhea: 2, heart failure: 2, multiorgan failure (MOF): 1, unspecified case: 1. With a median follow-up of 32 months (range 1-185), the 6-year estimate of OS was 64% (95% CI 51-75). In univariate analysis, none of the usual prognostic factors (gender, age ≥ 65, disease status before transplant, CD34+ cells count, time to relapse < 1 year, disease stage at relapse, Hb level) significantly influenced OS. At last follow-up, 13 patients died: 5 from toxicity (1 MOF, 2 interstitial pneumonia, 1 heart failure and 1 invasive pulmonary aspergillosis), 4 from disease progression, and 4 from unspecified causes. Conclusion: This retrospective study with long term follow-up, despite its limitations, suggests that in selected elderly patients ASCT is a valid treatment option for chemosensitive R/R cHL patients, with an acceptable rate of toxicity warranting further investigations in the era of novel agents such as brentuximab. Disclosures Brice: Seattle Genetics, Inc.: Research Funding; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Roche: Honoraria.

Download Full-text

Low-Dose Anti-Thymocyte Globulin for Graft-Versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplant

Blood ◽

10.1182/blood.v128.22.5782.5782 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5782-5782

Author(s):

Adam Bryant ◽

Ranjeeta Mallick ◽

Lothar B. Huebsch ◽

David S. Allan ◽

Harold Atkins ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Research Funding ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Relapse Free Survival ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Free Survival ◽

Related Donor

Abstract Background Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic in-vivo T-Cell depletion with antithymocyte globulin (ATG) has recently been reported as leading to decreased GVHD rates in matched unrelated and related donor HSCT, without increases in relapse or death. Understanding that higher rates of GVHD are observed with matched unrelated versus matched related donor HSCT, we have always had a local policy to give ATG as part of GVHD prophylaxis in patients undergoing HSCT from an unrelated donor. Here we report and compare clinical outcomes of patients who did and did not receive ATG at our transplant center using a unique, substantially lower ATG dose than previously reported. Methods We conducted a retrospective single-center database study comparing outcomes in 110 matched unrelated donor (MUD; ATG-exposed) and 78 matched related donor (MRD; ATG-unexposed) HSCT patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. Patients were exposed to a rabbit ATG formulation (Thymoglobulin ®) at 0.5 mg/kg on day -2 and 2.0 mg/kg on day -1 prior to stem cell infusion, to total 2.5 mg/kg. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days post HSCT, respectively. Secondary outcomes included disease relapse and survival. Results At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen and intensity between ATG exposed (MUD) and unexposed (MRD) cohorts. The majority of patients in both cohorts had intermediate or high disease risk index. There were significant baseline differences between the ATG exposed and unexposed cohorts with respect to proportion of 7/8 mismatched unrelated donor transplants (14 v 6% respectively, p = 0.015) and median CD34+ dose (4.9 v 7.6 x 108 cells; p < 0.001). No differences were noted in platelet engraftment. ATG exposed patients had significantly shorter time to neutrophil engraftment than the unexposed cohort (16 v 19 days respectively; p=0.007). ATG exposed patients had significantly lower rates of GVHD compared to the unexposed cohort (57 v 79%; p=0.005), with differences noted predominantly in rates of chronic GVHD (18 v 44%, p= 0.009). The proportion of patients off immune suppression one year after HSCT was not significantly different between the cohorts.At median follow-up of 13 (1-73) months for the ATG exposed cohort and 20 (0-69) months for the ATG unexposed cohort, no significant differences in overall survival (median overall survival not met for either cohort), cumulative incidence of relapse (26 v 29%; p=0.73) or relapse-free survival (not met in ATG exposed; 26.2 months in ATG unexposed, p=0.22) were observed between groups (Figure 1). Significant differences were observed with respect to GVHD-Free Relapse-Free Survival (GRFS) between ATG exposed and unexposed cohorts, with a two-year GRFS of 23 v 3% respectively (p = 0.003). There were no significant differences between cohorts in proportion of patients with post HSCT infectious episodes or ICU admissions. Conclusions Here we report significantly lower rates of chronic GVHD and significant improvement in GVHD-free relapse-free survival in our ATG exposed MUD HSCT cohort compared to our ATG unexposed MRD. These findings were observed without differences in relapse or survival outcomes, infectious complications or ICU admissions. While in keeping with other recent reports on ATG use for GVHD prophylaxis, our findings indicate that a lower dose of ATG may be effective in preventing GVHD. Our study suggests that a broader exploration into the optimal dosing of this prophylactic GVHD agent is warranted. Disclosures Bence-Bruckler: Lundbeck: Membership on an entity's Board of Directors or advisory committees. Sabloff:Novartis Canada: Membership on an entity's Board of Directors or advisory committees; Lundbeck: Research Funding; Alexion: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding.

Download Full-text

Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis

Blood ◽

10.1182/blood-2021-151808 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2465-2465

Author(s):

Christopher J. Forlenza ◽

Jaclyn Rosenzweig ◽

Audrey Mauguen ◽

Ilia Buhtoiarov ◽

Branko Cuglievan ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Salvage Therapy ◽

Research Funding ◽

Pediatric Patients ◽

Median Number ◽

Brentuximab Vedotin ◽

Refractory Disease ◽

Free Survival ◽

Frontline Therapy

Abstract Background: Although the prognosis for children with Hodgkin lymphoma (HL) is excellent, up to 25% of patients experience relapse and require salvage therapy. Event-free survival (EFS) for patients with relapsed or refractory disease (R/R) who require high-dose therapy with autologous stem cell transplantation (ASCT) is between 31-67% (Daw, 2011), and efforts to improve these outcomes are an area of urgent clinical need. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate combined with monomethyl auristatin E. The phase III AETHERA study (NCT01100502) was a randomized, placebo-controlled trial that demonstrated consolidation with BV following ASCT for adults with R/R HL improved progression-free survival (PFS) in comparison to placebo (5-year PFS 59% vs. 41%) in patients identified as having a high-risk of post-ASCT progression (Moskowitz, 2015, 2018). However, there is limited data on post-ASCT BV consolidation in pediatric patients. Here, we report a retrospective multi-center study of BV as consolidation post-ASCT in pediatric patients with R/R HL. Patients and Methods: We performed a retrospective analysis of pediatric patients aged ≤ 21 years who received BV as consolidative therapy following ASCT for the treatment of relapsed/refractory HL. Data was collected on disease risk factors (refractory disease or relapse ≤ 12 months after frontline therapy, best response of partial remission or stable disease to salvage therapy, presence of extranodal involvement, presence of B symptoms, and number of systemic treatments pre-ASCT ≥ 2), treatment history, BV-related toxicity, and response to therapy. The primary endpoint was 3-year EFS. Events were defined as relapse, progression of disease, or death from any cause. Results: Seventy patients were identified from 14 academic centers. Eighteen received BV >90 days after ASCT and were excluded due to significant delay in initiation of BV. Of the remaining 52 patients, the median age at diagnosis was 15 years (range 4-21), and the median age at diagnosis of R/R disease was 16 years (range 8-22). Twenty-eight patients (54%) were male, 13 (25%) had B symptoms, 19 (37%) had extranodal disease. Six patients (12%) had primary refractory disease and 24 patients (47%) relapsed <12 months after frontline therapy. The median number of salvage regimens received pre-ASCT was 2 (range 1-7). Forty-two patients (81%) received BV as part of a pre-ASCT salvage regimen, 4 (8%) of whom did not receive BV in the regimen immediately prior to ASCT. Radiation therapy was used pre or post-ASCT in 16 patients (31%). Prior to ASCT, 40 patients (77%) were PET-negative (Deauville 1-3), 11 (21%) were PET-positive (Deauville 4-5), and response in 1 (2%) was unknown. The median time from ASCT to the start of BV consolidation was 52 days (range 30-90 days). The most frequent adverse events were peripheral neuropathy of any grade (sensory 19/52 [37%]; motor (14/52 [27%]), and cytopenias (grade 3 or 4: (25/52 [48%]), including neutropenia (13/52 [25%]), thrombocytopenia (7/52 [14%]), and anemia (5/52 [10%]). Three patients (6%) experienced infusion-related reactions. The median number of BV cycles completed post-ASCT was 12 (range 1-17), and 16 patients (31%) completed the full 16 cycles of BV. The most common reason for premature termination was adverse effects (22/36 [61%]). Additional reasons included: physician plan for shorter duration (4/36 [11%]), patient/family decision (3/36 [8%]), and progression (1/36 [3%]). Treatment was still ongoing in 3 patients and reason for premature termination was not reported for 17/36 patients (47%). With a median follow of 2.8 years (range 0.1 to 6.25 years) the three-year EFS was 92% [95%CI: 83-100]. Patients with 0-1 risk factors (15/52 [29%]) and ≥ 2 risk factors (37/52 [71%]), had a 3-year EFS of 100% and 90% [95%CI: 79-100], respectively. Fifty patients (96%) are alive with no evidence of disease, while 2 (4%) patients are alive with disease. No deaths have occurred. Conclusion: The use of post-ASCT BV consolidation for pediatric patients with R/R HL is associated with a favorable safety and tolerability profile. In this cohort, the combination of salvage therapy, HD-chemotherapy/ASCT, and BV consolidation resulted in extremely promising outcomes and warrants further investigation in a prospective pediatric trial. Figure 1 Figure 1. Disclosures Leger: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbott Diagnostics: Research Funding. Roth: Merck: Consultancy; Janssen: Consultancy.

Download Full-text

Updated 18-Month Results from Dasfree: A Study Evaluating Dasatinib Discontinuation in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) and Deep Molecular Response (DMR)

Blood ◽

10.1182/blood-2018-99-116563 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4253-4253 ◽

Cited By ~ 5

Author(s):

Neil P. Shah ◽

Jose Valentín García Gutiérrez ◽

Antonio Jiménez-Velasco ◽

Sarah Larson ◽

Susanne Saussele ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Kinase Inhibitor ◽

Safety Data ◽

Chronic Phase ◽

Molecular Response ◽

Relapse Free Survival ◽

Advisory Committees ◽

Free Survival

Abstract Introduction: Tyrosine kinase inhibitor (TKI) discontinuation is being investigated in pts with CML-CP with sustained DMR (defined here as MR4.5 or BCR-ABL1 ≤ 0.0032% on the International Scale [IS]), with the goal of treatment-free remission (TFR). Successful TFR has been reported previously for pts enrolled in DASFREE (CA180-406/NCT01850004), which showed that 48% of CML-CP pts with DMR for ≥ 1 year were able to stop dasatinib and maintain major molecular response (MMR) 12 months after discontinuation. Here we present updated results from pts followed for a minimum of 18 months, in order to understand the durability of TFR beyond 12 months. Methods: DASFREE is a phase 2, open-label, single-arm study in adult pts with CML-CP on dasatinib for ≥ 2 years as 1st-line or subsequent therapy. Eligible pts had dasatinib-induced DMR (MR4.5) confirmed at a local lab for ≥ 1 year prior to enrollment, with a 1-log reduction in BCR-ABL1 from baseline within 3-6.5 months of starting dasatinib. MR4.5 was confirmed at a central lab twice within 3 months prior to dasatinib discontinuation (screening phase). BCR-ABL1 was monitored centrally after discontinuation every month in the 1st year, then every 3 months. Pts resumed dasatinib at their previous dose if MMR was lost. The primary endpoint is the rate of MMR 12 months after dasatinib discontinuation. Secondary endpoints include BCR-ABL1 kinetics, molecular relapse-free survival (MRFS; no loss of MMR), relapse-free survival (RFS; no loss of MMR, complete cytogenetic response, or complete hematologic response, or progression to accelerated/blast phase [AP/BP] CML), rate of transformation to AP/BP, progression-free survival, and overall survival. Exploratory analyses include frequency of adverse events (AEs) after discontinuation and during dasatinib treatment, and MMR after reinitiating dasatinib. Results: In total, 84 pts enrolled between February 2014 and June 2016 discontinued dasatinib; all had ≥ 18 months of follow-up after discontinuation at the time of this analysis. Pt characteristics were previously reported (the majority [64%] had low Sokal scores; no pt had prior interferon; 37 pts were on 1st-line dasatinib, 47 on subsequent lines of dasatinib). At 18 months after discontinuation, the RFS rate was 48% (95% CI 37-58) in all pts (Figure), 54% (95% CI 38, 70) in 1st-line pts, and 42% (95% CI 28, 57) in pts who received subsequent-line therapy. With longer follow-up, 1 additional pt lost MMR at 18 months following discontinuation. Of the 45 pts who lost MMR and restarted treatment, 44 regained MMR (1 pt discontinued after only 1 molecular assessment) in a median of 2 months (range 1-4) and 42 regained MR4.5 in a median of 3 months (range 2-18). Analyses of baseline pt characteristics revealed that for the 40 pts who did not lose MMR after discontinuation, 15 (37.5%) were able to maintain MR4.5. Additionally, the median time in prior MR4.5 was 28 months (range 13-116) for all pts, and was similar for 1st-line pts who maintained (27 months [range 13-56]) or lost MMR (27 months [range 15-68]) at 12 months. With longer follow-up, AEs (any cause) identified were consistent with previous reports and were found to be similar on and off treatment: 8 (10%) pts off treatment and 8 (18%) pts on treatment experienced grade 3/4 AEs of any cause after restarting dasatinib (4.4% were drug related). No transformation events or deaths occurred. Of the 13 reported withdrawal events occurring in 8 (9.5%) pts, 10 were resolved (5 off treatment, 5 resolved after restarting treatment due to loss of MMR) after a median of 5 months (range 1-12) after onset. One pt discontinued after restarting dasatinib due to malignancy unrelated to treatment. In addition to efficacy and safety data, multivariate analyses evaluating prognostic factors for MMR will be presented. Conclusions: Additional follow-up of pts enrolled in DASFREE revealed that TFR remained durable at 18 months after discontinuing dasatinib. AEs reported here were consistent with the known safety profile of dasatinib, and withdrawal was well tolerated. Collectively, this trial, the largest dasatinib discontinuation trial to date, continues to support the feasibility and practicality of TFR in pts with CML-CP in DMR treated with dasatinib in the 1st line and beyond. Figure. Figure. Disclosures Shah: ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding. García Gutiérrez:Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Larson:Bristol-Myers Squibb: Consultancy; Takeda: Speakers Bureau. Saussele:Bristol-Myers Squibb: Honoraria, Research Funding; Incyte: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria. Rea:Incyte: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Mahon:Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Levy:Takeda (Millennium Pharmaceuticals, Inc.): Consultancy. Gómez-Casares:Novartis: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau. Pane:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy. Nicolini:Incyte: Consultancy, Honoraria, Speakers Bureau; Sun Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau. Mauro:Pfizer: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding. Sy:Bristol-Myers Squibb: Employment. Martin Regueira:Bristol-Myers Squibb: Employment, Equity Ownership. Lipton:ARIAD: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Download Full-text

Brentuximab Vedotin As Consolidation Therapy Post Hematopoietic Stem Cell Transplantation for Patients with Relapsed or Refractory Hodgkin Lymphoma: A Real World Analysis of the Colombian Experience

Blood ◽

10.1182/blood-2019-129295 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5275-5275

Author(s):

Bonell Patiño ◽

Cristina Acon-Solano ◽

Mario Pereira ◽

Leonardo Enciso-Olivera ◽

Diana Otero-de la Hoz ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Retrospective Cohort ◽

Progression Free Survival ◽

Brentuximab Vedotin ◽

Advisory Committees ◽

Free Survival

Introduction: High-dose chemotherapy followed by autologous stem-cell transplantation (auto-HCT) is standard of care for patients with relapsed or primary refractory classical Hodgkin lymphoma (cHL). Brentuximab vedotin (BV) consolidation after auto-HCT improves progression-free survival of cHL patients with primary refractory disease and high risk for relapse as seen in the AETHERA trial. There are no published reports of BV consolidation post auto-HCT in cHL patients treated in developing countries. The aim of this study is to determine the clinical outcomes and safety of BV consolidation after auto-HSCT in a cohort of Colombian patients with relapsed or refractory (R/R) cHL. Methods: A retrospective cohort study was conducted at ten tertiary referral centers in five cities in Colombia. Data from patients with R/R cHL who underwent auto-HCT followed by BV consolidation was collected and analyzed. Descriptive statistics were used to analyze patient's demographic characteristics. The Kaplan-Meier method was used to assess overall survival (OS) and progression-free survival (PFS) rates and log-rank test was used to compare survival between groups. All data were analyzed by R Studio software. Results: Fifty-three patients with a confirmed diagnosis of cHL were included, 49,1% were women. Median of age at auto-HCT was 29 years (range 17 - 66). The most frequently used frontline regimen was ABVD 90,6%. Median number of treatment lines including auto-HCT was 3 (range 2 to 7). 83% of patients had BV consolidation after 1stAUtoHCT and 17% after 2 auto-HCT. The most common high-risk feature before auto-HCT was primary refractory cHL (54,7%). Responses were determined by Lugano criteria. However, unconfirmed complete responses (uCR) per 2007 IWC criteria were used due to lack of PET-CT availability of evaluation in some centers, where CT scan were used. The overall rate (ORR) before auto-HCT was 94,4% with complete response (CR) in 28,3%, uCR 20,8% and partial response (PR) in 45,3% of patients. The ORR after auto-HCT was 90,5% with CR in 52,8%, uCR in 22,6%, and PR 15,1%. Table1. A total of 531 BV cycles were administered as post auto-HCT consolidation with a median of 11 cycles (range 1-16). A median of 23 days between each cycle was documented (range 7-210 days). The most common grade 3-4 toxicities were peripheral neuropathy (18,8%), fatigue (9,4%), weight loss (5,6%). OS at 132 months was 92,5% (CI95%: 4,9 - NR) (Figure A), and the median PFS was not reached (CI 95%: 36.5 months - Not reached) with 75,5% PFS at 132 months, with a mean of follow-up of 23,5 months (Range: 4,2 - 133,2 months) (Figure B). There was a trend towards worse PFS in patients treated with ≥ 3 regimens before auto-HCT Median: 38.7 months, (CI 95%: 36.5 - NA) Vs. 2 lines: Median: NR (CI 95%: 4,2-NR) P= 0.4.(Figure C). Also patients that required a second transplant followed by BV consolidation had a worse PFS, compared to the ones that underwent BV consolidation post first auto-HCT: median: 13.6 months (CI 95%: 6.7- NR)Vs. median: NR (CI95%: 38,7 - NR) respectively p=0,009 (Figure D). Twelve patients relapsed and 4 patients died form disease progression. Conclusions: BV consolidation after auto-HCT in high-risk R/R cHL patients treated in a developing country setting seems to be a safe and effective treatment. Although OS and PFS were slightly superior to the ones reported in the AETHERA trial, the mean of follow-up in our analysis is shorter. Another shortcoming of our analysis are the inherit limitation of a retrospective cohort. These retrospective results need to be assessed in prospective trials that specifically includes Latin-American with high-risk patients with R/R cHL. Disclosures Patiño: Amgen: Speakers Bureau. Enciso-Olivera:Takeda: Speakers Bureau. Otero-de la Hoz:Takeda: Speakers Bureau. Martínez Cordero:Takeda: Speakers Bureau. Karduss:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Abello:Takeda: Other: Participation in advisory board meeting. Sandoval-Sus:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽

10.1182/blood-2018-99-116496 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2149-2149

Author(s):

Romil Patel ◽

Neeraj Y Saini ◽

Ankur Varma ◽

Omar Hasan ◽

Qaiser Bashir ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Advisory Committees ◽

First Remission ◽

Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

Download Full-text

Outcome of Hodgkin Lymphoma after Progression Following Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.2994.2994 ◽

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.

Download Full-text

Evaluating Gvhd Outcomes Using Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil As Gvhd Prophylaxis Compared with Methotrexate/Tacrolimus in Matched-Related and Matched-Unrelated Hematopoietic Stem Cell Transplant in Relation to the Haplo-Identical Setting: A Single Center Experience

Blood ◽

10.1182/blood-2020-141659 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-6

Author(s):

Mindy Hsiao ◽

Preet M. Chaudhary ◽

George Yaghmour

Keyword(s):

Stem Cell ◽

Mycophenolate Mofetil ◽

Board Of Directors ◽

Relapse Free Survival ◽

Advisory Committees ◽

End Points ◽

Free Survival ◽

Gvhd Prophylaxis ◽

Grade 3 ◽

Haplo Group

Background: The use of post-transplant cyclophosphamide (PTCy)/tacrolimus/mycophenolate mofetil (MMF) for GVHD prophylaxis has improved outcomes in haploidentical hematopoietic cell transplantation (haplo-HCT). PTCy is now being evaluated in matched-related (MRD) and matched-unrelated (MUD) allo-HCT. Previous studies demonstrated improved GVHD-free/relapse-free survival (GRFS) when PTCy was combined with two immunosuppressive agents and PTCy has also been associated with better relapse-free survival (RFS) as demonstrated in De Jong et al 2019, though only one immunosuppressive agent was used. Currently, there is limited published data comparing outcomes using PTCy/tacrolimus/MMF to standard MRD/MUD GVHD prophylaxis of methotrexate (MTX)/tacrolimus. The importance of studying this comparison may help to improve GVHD outcomes in MRD and MUD allo-HCT. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 19) who received allo-HCT from 2018 to 2020. The primary end-points assessed were incidence and severity of 1-year aGVHD and cGVHD. Secondary end-points included day+100 mortality, 1-year overall survival (OS), 1-year RFS, 1-year transplant-related mortality (TRM), and 1-year GRFS, defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the 1-year post-HCT period. Results: A total of 65 adult MRD and MUD allo-HCT recipients and 53 haplo-HCT patients were reviewed. Of the MRD/MUD patients evaluated, approximately 51% (n = 33) were female and 49% (n = 32) were male. The age range was 20-69 years old (median = 46), and the most common diseases included ALL (46%), AML (31%), MDS (11%), and others (i.e. lymphoma, aplastic anemia (AA), myelofibrosis) (12%). 34% (n = 22) of patients received PTCy on D+3 and D+4 with tacrolimus/MMF/ on D+5 as GVHD prophylaxis and 66% (n = 43) of patients received MTX/tacrolimus on D+1, +3, +6, and +11 as GVHD prophylaxis. All haplo-HCT patients received standard PTCy/tacrolimus/MMF. Stem cell source was primarily PBSC except in HLH and AA patients. The PTCy group had more MUD allo-HCT (64%), degree of antigen mismatch (56%), and median age of 50.5 years compared with the MTX group at 44%, 47%, and 44 years respectively. 70% in the MTX group received MAC compared with 45% in the PTCy group. The haplo group had similar demographics to the MTX group. The mean CD34 cell doses in the PTCy, MTX, and haplo groups were 4.87, 5.36, and 7.24x106 cells/kg respectively. Incidences of total GVHD, aGVHD, and aGVHD grade 3 or 4 in the PTCy group were 55%, 50%, and 4.5% respectively compared with 65%, 35%, and 7% in the MTX group, though not significant. The haplo group had 68%, 55%, and 1.9% respectively. Incidence of total cGVHD and cGVHD requiring systemic therapy in the PTCy group was 4.5% and 0% respectively compared with 30% (p = .02) and 23% (p =.01). The haplo group had 13% and 1.9% respectively. Day+100 mortality, 1-year OS, 1-year RFS, 1-year TRM, and 1-year GRFS in the PTCy group were 0%, 80%, 60%, 0%, and 64% respectively compared with 7%, 88%, 90%, 7.3%, and 59%. The haplo group had 3.8%, 86%, 89%, 14%, and 66%. In a univariate analysis, factors significantly associated with GVHD were disease status (p = .0.12) and CD34 dose (p = 0.015) and antigen mismatch (p = 0.04) was associated with increased mortality. Discussion: Our results demonstrate improved overall and extensive cGVHD outcomes in the PTCy group and thus an improvement in 1-year GRFS. Furthermore, incidence and severity of 1-year cGVHD in this group are improved when compared with previously reported outcomes. 1-year GRFS reported in De Jong et al 2019 was 45% and 1-year GRFS reported for all groups in our study is higher at 66%, 64%, and 59% for the haplo, PTCy, and MTX groups respectively. Although this was not significant, it may be clinically meaningful given the significant improvement in extensive GVHD and improvement in all other secondary end-points except 1-year OS and RFS. Furthermore, the PTCy group had a higher percentage of mismatched antigens yet demonstrated superior outcomes. 1-year OS and RFS were superior in the MTX group however this is likely due to sample size differences. The improved extensive cGVHD and GRFS outcomes observed using PTCy/tacrolimus/MMF in the MRD/MUD setting should continue to be evaluated and currently there is an ongoing prospective, randomized study to further investigate. Disclosures Yaghmour: Jazz: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Download Full-text

ABVD Versus Escalated Beacopp in Advanced Stage Hodgkin's Lymphoma: Results from a Retrospective, Multicenter European Study

Blood ◽

10.1182/blood-2019-128198 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1565-1565 ◽

Cited By ~ 1

Author(s):

Patrizia Mondello ◽

Irene Dogliotti ◽

Jan-Paul Bohn ◽

Federica Cavallo ◽

Simone Ferrero ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Advanced Stage ◽

Advisory Committees ◽

Free Survival ◽

High Risk Patients ◽

Risk Patients

Purpose: Hodgkin's lymphoma (HL) is a highly curable disease even in advanced-stage, with >90% of long-term survivors. Currently, the standard of care is ABVD (doxorubicin, etoposide, vinblastine and dacarbazine), as it is less toxic and as effective as other more intensive chemotherapy regimens. Alternatively, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) has been proposed as front-line intensified regimen with a better initial disease control and prolonged time to relapse when compared to ABVD. However, this advantage is associated with higher rates of severe hematologic toxicity, treatment-related deaths, secondary neoplasms and infertility. To date, the debate regarding which regimen should be preferred as first line for advanced-stage HL is still ongoing. To shed some light on this open question we compared efficacy and safety of both regimens in clinical practice. Patients and Methods: From October 2009 to October 2018, patients with HL stage III-IV treated with either ABVD or BEACOPP escalated (BEACOPPesc) were retrospectively assessed in 7 European cancer centers. Results: A total of 372 consecutive patients were included in the study. One-hundred and ten patients were treated with BEACOPPesc and 262 with ABVD. The baseline characteristics of the two groups did not differ significantly, except for a higher rate of high-risk patients in the BEACOPPesc group in contrast to the ABVD one (47% vs 18%; p= 0.003). Complete response rate (CR) assessed by PET imaging at the end of the second cycle was 67% and 78% for the ABVD and BEACOPPesc group (p= 0.003), respectively. Thirteen patients of the ABVD group achieved stable disease (SD) and 6 had a progression disease (PD). On the other hand, 4 of the patients in the BEACOPPesc group progressed, another 2 interrupted therapy because life-threatening toxicity. At the end of the therapy, CR was 76% in the ABVD group and 85% in the BEACOPPesc group (p= 0.01). A total of 20% patients in the ABVD group and 14% patients in the BEACOPPesc group received consolidation radiotherapy on the mediastinal mass at the dose of 30Gy. After radiotherapy, the number of patients with CR increased to 79% and 87% in the two groups (p= 0.041), respectively. Thirty-nine patients (35%) in the BEACOPPesc group required dose reduction of chemotherapy due to toxicity compared to 12 patients (5%; p= <0.001) in the ABVD group. Overall, the rate of severe toxicities was higher in the BEACOPPesc group in comparison with the ABVD cohort. In particular, there was a significant increased frequency of acute grade 3-4 hematologic adverse events (neutropenia 61% vs 24%; anemia 29% vs 4%; thrombocytopenia 29% vs 3%), febrile neutropenia (29% vs 3%), severe infections (18% vs 3%). Myeloid growth factors were administered to 85% and 59% of patients in the BEACOPPesc group compared to the ABVD group. Blood transfusions were required in 51% and 6% of patients in the BEACOPPesc group compared to the ABVD cohort. Progression during or shortly after treatment occurred in 5 patients in the BEACOPPesc group (4%) and in 16 patients in the ABVD group (6%; p= 0.62). Among the 96 patients who achieved a CR after BEACOPPesc and radiotherapy, 8 relapsed (8%), compared to 29 of 208 patients in the ABVD group (14%; p= 0.04). At a median follow-up period of 5 years, no statistical difference in progression free survival (PFS; p=0.11) and event-free survival (EFS; p=0.22) was observed between the BEACOPPesc and ABVD cohorts. Similarly, overall survival (OS) did not differ between the two groups (p=0.14). The baseline international prognostic score (IPS <3 vs ≥ 3) significantly influenced the EFS with an advantage for the high-risk group treated with BEACOPPesc (Figure 1A; p=0.03), but not the PFS (Figure 1B; p=0.06) and OS (Figure 1C; p=0.14). During the follow-up period, in the BEACOPPesc group one patient developed myelodysplasia and one acute leukemia. Second solid tumors developed in one patient in the ABVD group (lung cancer) and one in BEACOPPesc group (breast cancer). Conclusion: We confirm that the ABVD regimen is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control especially in high-risk patients, the long-term outcome remains similar between the two regimens. Disclosures Ferrero: EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau. Martinelli:BMS: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy; Roche: Consultancy; Novartis: Consultancy. Willenbacher:European Commission: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Myelom- und Lymphomselbsthilfe Österreich: Consultancy, Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Science: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; IQVIA: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; oncotyrol: Employment, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujimoto: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tirol Program: Research Funding; Abbvie: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Download Full-text