Prednisone, Vinblastine, Doxorubicin and Bendamustine (PVAB) Regimen in First Line Therapy for Older Patients with Advanced-Stage Classical Hodgkin Lymphoma: Results of a Prospective Multicenter Phase II Trial of the Lymphoma Study Association (LYSA)

Introduction: Older patients with an age above 60 years with classical Hodgkin lymphoma (cHL) represent a proportion of 20% to 30% of all cHL. Older cHL patients are characterized by unfavorable prognostic factors with an aggressive disease, a poor tolerance to chemotherapy resulting to a significant reduced survival as compared to younger patients. In relapsed and refractory HL, prospective and retrospective studies showed that bendamustine in monotherapy provided interesting efficacy with 30% of complete response with an acceptable toxicity profile. We developed the PVAB (Prednisone, Vinblastine, Doxorubicin and Bendamustine) regimen in first line therapy to improve prognosis of older HL with advanced stage. Methods: In this prospective phase II, we recruited newly diagnosed classical HL patients age of 61 years or older with an advanced stage (Ann Arbor stage III, IV, IIB with risk factors). Inclusion criteria were: baseline 18-FDG PET scan performed before any treatment with at least one hypermetabolic lesion; ECOG performance status 0-2; adequate cardio-pulmonary function with LVEF ≥ 50%; adequate renal function with creatinine clearance ≥ 40 mL/min; HIV negative; For patients aged 70 years old and more, a Mini Nutritional Assessment (MNA) ≥ 17. Treatment consisted of 6 cycles of prednisone (40mg/m2 D1-5), vinblastine (6mg/m2, D1), doxorubicin (40mg/m2, D1) and bendamustine (120mg/m2, D1) every 21 days. A first evaluation was performed after 4 cycles by CT scan and a final evaluation by PET scan after 6 cycles. No radiotherapy was applied in this protocol. The primary endpoint was the complete metabolic response (CMR) rate after 6 cycles of study treatment or at premature treatment discontinuation according to Lugano Classification. The main analysis for the CMR rate was based on a Simon's phase II design. We selected P0 and P1 to be 70% and 85%, respectively for CMR rate. A total of 79 patients provided nominal power of 80% at the nominal one-sided 5% significance level. Using a drop-out rate of 10%, 90 patients should be included in this trial. Results: Between July 2015 and July 2018, 89 patients who signed the consent form and received at least one PVAB cycle corresponding to intention to treat (ITT) group were included in 34 LYSA centers. Among them, four patients did not respected major inclusion criteria (one patient had a nodular lymphocyte predominant subtype after histological review and three patients ≥ 70 years had no MNA evaluation at inclusion) corresponding to the modified ITT group (N=85). The median age of the 89 patients was 68 years (range, 61-88) with 35 patients ≥70 years old (39%) and 58 male (65%). According to the central review, the main histological subtype was nodular sclerosis cHL (66%). Ann Arbor stages were as follows: II (n=3, 3%), III (n=30, 34%), IV (n=56, 63%). B symptoms were present in 57% of patients and 70 patients (80%) had IPS≥3. 78 patients (88%) completed the 6 cycles of PVAB. In ITT, the CMR rate corresponding to the primary endpoint of the study was 77.5% (95%CI, 67-86) with 69 patients in CMR; 8 patients were in partial metabolic response; 2 and 5 patients had a stable and progressive disease, respectively and 5 were not evaluable. In the modified ITT group, the CMR rate at this end of treatment was 77.6% (95%CI, 67-86). With a median follow-up of 23 months (0.5-40.3), 25 patients relapsed or progressed (28%). The 2-year progression survival rate (PFS) rate was 61.3% (95%CI, 49-72). For the 69 patients achieving CMR, the 2-year disease free survival (DFS) rate was 73.3% (95%CI, 61-82). At the date of analysis (December 2018), 17 patients (19%) died: 7 cHL, 4 treatment toxicity, 3 second cancers, 3 other causes. The 2-year overall survival rate was 84.1% (95%CI, 73-91). For toxicity, 4 patients presented toxic death during treatment: one cardiogenic shock (71y, >cycle 1) one septic shock (70y, >cycle 1), one brain hematoma with grade 4 thrombocytopenia (76y, >cycle 1), one fungal infection (86y, >cycle 4). At least one serious adverse events (SAE) were presented by 28 patients (31.5%) mainly infections (13 patients, 15%), blood (11 patients, 12%) and cardiac disorders (4 patients, 4.5%). Conclusions: Six cycles of PVAB regimen provided high CMR (77.5%) with acceptable toxicity in older cHL patients with advanced stage. Patients with CMR at the end of treatment had a particular favorable outcome but long term follow-up is needed for a better evaluation of survival endpoints. Disclosures Morschhauser: Roche/Genentech: Consultancy; Celgene: Honoraria; Servier: Consultancy; Gilead: Consultancy; Janssen: Honoraria; BMS: Honoraria. André:Celgene: Other: Travel grants, Research Funding; Chugai: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants, Research Funding; Amgen: Other: Travel grants, Research Funding; Johnson & Johnson: Research Funding; Takeda Millenium: Research Funding. Quittet:Novartis: Honoraria, Speakers Bureau. Brice:Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. OffLabel Disclosure: Bendamustine is off-label drug use in Hodgkin lymphoma

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Adult T-Cell Leukemia/Lymphoma: A Cohort of 41 Cases Recorded in the Brazilian T-Cell Project

Blood ◽

10.1182/blood-2020-142818 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 35-36

Author(s):

Daniel Silva Nogueira ◽

Marcia Torresan Delamain ◽

Eliana Cristina Miranda ◽

Yung Bruno de Melo Gonzaga ◽

Juliana Pereira ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Board Of Directors ◽

Research Funding ◽

Advanced Stage ◽

Line Treatment ◽

Cell Leukemia ◽

Advisory Committees ◽

Stage Disease ◽

Ann Arbor

Introduction:Adult T cell Leukemia/Lymphoma (ATLL) is a mature T-Cell-neoplasm related to human T-cell lymphotropic virus type 1 (HTLV-1) infection that shows variable clinical presentation and adverse prognosis with shorter overall survival (OS) when compared to other peripheral T-cell lymphomas (PTCL). Previous epidemiological studies estimated cumulative incidence in endemic regions around the world. In Brazil, mainly due to its vast dimension, data collection has limitations and is subject to bias. In April 2015 theBrazilianT-cell longitudinal project initiative was launched. One of the primary purposes was the collection of epidemiological and clinical data from the most frequent subtypes of newly diagnosed PTCL. Among them, 41 cases of ATLL were recorded. Objectives:The aim of this study is to describe clinical features, frequency and overall survival (OS) of 41 cases of ATLL registered in the ongoingBrazilianT-Cell Project. Methods:This is an ambispective observational study design collecting baseline characteristics, clinical features including date of diagnosis, clinical subtypes, B symptoms, performance status, Ann-Arbor staging, HTLV-1 status, number of sites, nodal and extra nodal presentation and types of skin lesions, peripheral blood counts and biochemical tests, front-line treatment and best response after first-line treatment. REDcap Platform has been used to collect and store data and for descriptive analysis the IBM-SPSS version 24 was applied. Kaplan-Meier method estimated the OS, whereas Log-Rank tests to compare its curves. OS period was calculated from diagnosis date until death or last seen date, and event was death by any cause. Results:Out of 281 cases of PTCL registered so far, 41 were ATLL cases. The median age was 50 years (34-88), 25 (64%) female; a higher incidence of lymphoma subtype was observed (46%), followed by acute (29%), chronic (17%) and smoldering (8%). Most of the patients (85%) had advanced-stage disease (III-IV, Ann-Arbor) and 56% had B symptoms (Table 1); 73% received chemotherapy with anthracycline-based regimens (46.5% CHOEP; 33.5% CHOP; 20% others) whereas 17% were managed with immunotherapy and antiviral therapy. The overall response rate was 30%; no response or progression 46%; stable disease 9% and 15% no data available yet (Table 2). Median follow-up was 13 months and 25 months for 41% of alive patients. Two year OS was 39% (95%CI: 23-55%) (Figure 1). Smoldering and Chronic subtypes showed better OS when compared with acute and lymphoma (100% smoldering, 86% chronic; 30% lymphoma type and 13% acuteP=0.04) (Figure 2). The multivariate Cox Regression analysis found male gender (HR 10.9 95%CI: 3.0-39.7, P<0.0001) and albumin (HR 0.23 Beta -1.45 95%CI: 0.10-0.55, P=0.001) as significant prognostic factors for OS. Discussion:ATLL prognosis remains poor regardless of the type of treatment regimen and may be associated with the high incidence of lymphoma and acute subtypes, as well as advanced stage disease presentation. Despite the high number of cases seen in southeastern region of Brazil, it is important to emphasize there are still limited data from other regions. Albeit the sample size is small, these findings confirmed literature review data so far, with poor overall survival in a short time and gender and albumin as predictors of OS in the multivariate analysis. Conclusion:This study highlights the poor prognosis associated with ATLL. Moreover, it seems relevant to expand this study to all Brazilian regions. Hence, the need for early diagnosis and new treatment strategies, able to reduce mortality is warranted, that could possibly change the nature and spectrum of disease. Disclosures Federico: Spectrum:Consultancy, Membership on an entity's Board of Directors or advisory committees;Sandoz:Consultancy, Membership on an entity's Board of Directors or advisory committees;Cephalon/Teva:Research Funding;Mundipharma s.r.l.:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Millennium/Takeda:Research Funding;Roche:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda:Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Interim Analysis Results from an International, Multi-Centre, Non-Interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients with Classical Hodgkin Lymphoma: B-CD30+ Hodgkin Lymphoma International Multi-Centre Retrospective Study of Treatment Practices and Outcomes (B-HOLISTIC)

Blood ◽

10.1182/blood-2018-99-111146 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2917-2917

Author(s):

Burhan Ferhanoglu ◽

Tae Min Kim ◽

Gayane Tumyan ◽

Su-Peng Yeh ◽

David Brittain ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Resource Use ◽

Research Funding ◽

Chart Review ◽

Healthcare Resource ◽

Stage I ◽

Advisory Committees ◽

End Of Treatment ◽

Frontline Treatment

Abstract Background: The cure rate for advanced classical Hodgkin lymphoma (cHL) is approximately 70%, which is calculated based on data from clinical trials performed in North American and/or European countries (Canellos GP, et al. N Engl J Med. 1992;327:1478-84; Carde P, et al. J Clin Oncol. 2016;34:2028-36; Gordon LI, et al. J Clin Oncol. 2013;31:684-91). However, there are limited outcome data available in other countries, apart from some small hospital-based studies (Ramirez P, et al. Rev Bras Hematol E Hemoter. 2015;37:184-9; Law MF, et al. Arch Med Sci. 2014;10:498-504; Jaime-Pérez JC, et al. Oncologist. 2015;20:386-92; Omer Al-Sayes FM, Sawan A. J Taibah Univ Med Sci. 2006;1:48-56). The B-HOLISTIC retrospective chart review study seeks to address the paucity of data on cHL treatment patterns, clinical outcomes, and healthcare resource utilization in 13 countries across Latin America, Africa, Middle East, and the Asia-Pacific region. Methods: The study will collect data from approximately 2,600 patients aged ≥18 years and newly diagnosed with stage IIB-IV cHL or relapsed/refractory cHL (RRHL) between 01 January 2010 and 31 December 2013, and will follow them until death or chart review, whichever occurs first. The primary objective is to describe progression-free survival (PFS) in patients with RRHL. Secondary objectives include describing demographic and clinical characteristics, clinical outcomes (overall survival, best clinical response after completion of treatment, response duration), key adverse events associated with each line of therapy, and cHL-related healthcare resource use. Results: As of 14 May 2018, a total of 165 patients from 12 sites have been included in the interim analysis, predominantly from Turkey and South Korea. At this time, 150 patients had cHL and 24 patients had RRHL, including 9 patients who were enrolled in the cHL group and had a documented relapse/progression during the study period. Here, we report the results of the newly diagnosed cHL group; data from the RRHL group will be reported in subsequent publications. At diagnosis, 64.7% of the cHL group were male, with a median age of 36.5 years (range, 18-89 years); 22.7% had stage IV disease, 30% had extranodal disease, 59.3% had 'B' symptoms, and 34.9% had an International Prognostic Score (IPS) of ≥4. Patients were classified as 13.3% in stage I-IIA; 24% in stage IIB; 53.3% in stage IIIA-IVB; and 9.3% as unknown. Patients classified as stage I-IIA are a deviation from the clinical study protocol and will be removed from the final study analysis. The proportion of patients alive was 94%, with the cause of death reported as either HL-related (44.4%), due to an adverse event (11.1%), or other (44.4%). Positron emission tomography (PET) or PET-computed tomography (CT) imaging was performed in 58.5% of patients at baseline, 48% of patients at interim, and 36.6% at end-of-treatment; CT imaging was performed in 68.7% of patients at baseline, 83.6% of patients at interim, and 59.7% of patients at end-of-treatment. At frontline treatment, 95.3% of patients received chemotherapy (mostly doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], 92.3% [median number of cycles, 6; range, 2-8]), 22.7% of patients received radiotherapy, with 22% of patients receiving radiotherapy and chemotherapy (median total dose, 34.5 Gy; range, 24-45 Gy). The majority of patients received involved-field radiotherapy (53.1%), with other modalities including involved-node (21.9%), involved-site (18.8%), whole body (3.1%), or other (3.1%). The proportion of patients who achieved a complete or partial response to frontline treatment was 52.1% and 21.1%, respectively. The PFS for treatment in frontline cHL in the overall patient population at 48 months was 81% (95% CI, 73.1-86.7; Figure 1), with a median duration of follow-up of 58.9 months (range, 2.6-128.3 months). The PFS for treatment in frontline cHL excluding ineligible patients classified as stage I-IIA (13.3%) at 48 months was 78.9% (95% CI 69.7-85.6). Due to the retrospective nature of this study, adverse events were under-reported and will be presented once the data are mature. Conclusion: The B-HOLISTIC study is ongoing, with final patient enrolment anticipated in December 2018. These interim data provide real-world information on the incidence, treatment, and outcomes of cHL in countries where little is known about this patient population. Disclosures Ferhanoglu: Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Brittain:Takeda: Membership on an entity's Board of Directors or advisory committees. Karduss:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kwong:Bayer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Song:Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zerga:Bristol Myers Squibb: Other: Conference fees; Roche: Other: Conference fees; Janssen: Other: Conference fees; Takeda: Other: Conference fees. Blair:Takeda Pharmaceuticals International Co.: Employment. Dalal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Employment, Equity Ownership. Wan:Takeda Pharmaceuticals International Co.: Employment. Hertzberg:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees.

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AvR-CHOP: Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood-2019-127858 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5332-5332

Author(s):

Eliza A Hawkes ◽

Kate Manos ◽

Charmaine Smith ◽

Joanne Hawking ◽

Stephanie O'Brien ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Phase Ii ◽

Research Funding ◽

Metabolic Response ◽

B Cell Lymphoma ◽

Advisory Committees ◽

Complete Metabolic Response ◽

Pet Ct ◽

Large B Cell

Background: Whilst up to 60% of DLBCL patients (pts) are cured with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), outcomes remain poor for those with relapsed or refractory disease. 1 New strategies to improve frontline cure rates are needed. Tumour cells exploit immune checkpoint pathways, including the PD1/PDL1 axis, to evade the host immune system. PD1/PDL1 over-expression and cytogenetic 9p24 alterations in some DLBCL subtypes provide additional rationale for immune checkpoint inhibition (ICI) in this disease. Although single agent PD1 inhibition yields an overall response rate (ORR) of only 10%-30% in heavily pre-treated unselected DLBCL, many responses are durable.2 Immunosuppressive effects of prior therapy may contribute to the modest response to ICI in relapsed disease. A number of considerations influence the incorporation of ICI into upfront DLBCL treatment. Although concurrent PD1/PDL1 inhibition and R-CHOP is safe,3 corticosteroid-related immunosuppression may negate PDL1-inhibitor efficacy. Evidence supporting host immune priming with ICI prior to chemotherapy is promising,4 and maintenance ICI post chemotherapy may assist with immune reconstitution and enhance the anti-tumour immune response. Additionally, avelumab (Av, an anti-PDL1 monoclonal antibody with antibody dependent cellular cytotoxicity activity) acts synergistically with rituximab (R) in vitro (unpublished data, Pfizer 2016). Thus, we present our phase II study assessing the safety of sequential Av+R induction, R-CHOP and Av maintenance as upfront therapy for DLBCL. Methods: AvR-CHOP (NCT03244176) is a phase II multicentre single-arm trial of Av induction + maintenance with R-CHOP in newly-diagnosed adult pts with DLBCL. Pts aged >18 years, ECOG 0-2, stage II-IV and with no active autoimmune disease are eligible. Exclusion criteria include the necessity for urgent cytoreduction, grade 3B or transformed follicular lymphoma, CNS involvement, chronic steroid use, prior transplantation or pneumonitis. Treatment (Fig 1) comprises R (375mg/m2 IV) + Av (10mg/kg IV) x 2 cycles q2-weekly, followed by R-CHOP21 x 6 cycles. Maintenance Av x 6 cycles q2-weekly is given to patients achieving a complete metabolic response by PET/CT at the end of R-CHOP. PET/CT is performed after R+Av 2 cycles, cycle 2 R-CHOP, end of R-CHOP and end of Av maintenance. The primary endpoint is immune-related toxicity within 30 days post-treatment. Secondary endpoints include ORR, failure free survival (FFS), overall survival (OS) and toxicity of treatment. Complete metabolic response rates by PET-CT after R-Av induction and after C2 R-CHOP are exploratory endpoints. Biomarker sample collection is synchronised with PET response assessment. A comprehensive translational substudy will apply high throughput technologies to tissue and sequential blood samples to characterise the tumour-immune system interaction and correlate novel host, tumour and tumour microenvironment factors with treatment responses and toxicity. Planned enrolment is 28 pts across 3 sites in Australia. The study follows a Simon 1 stage design, with an 80% power and a 1-sided alpha of 0.05 to rule out an Av-related toxicity rate of 30% (p0=70%), assuming an expected immune related toxicity rate of 10% [p1=90%]. 23 pts are enrolled to date. Acknowledgements: Merck KgA (avelumab and funding) References: 1. Cunningham D et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet (London, England). 2013;381(9880):1817-26. 2. Ansell SM et al. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. J Clin Oncol. 2019;37(6):481-9. 3. Nowakowski GS et al. Safety and efficacy of PD-L1 inhibitor durvalumab with R-CHOP or R2-CHOP in subjects with previously untreated, high-risk DLBCL. Journal of Clinical Oncology. 2019;37(15_suppl):7520-. 4. Park SE et al. Increased Response Rates to Salvage Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non-Small Cell Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2018;13(1):106-11. Disclosures Hawkes: Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck KgA: Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Mundi pharma: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Takeda: Speakers Bureau; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees. Manos:NovoNordisk Pharmaceuticals: Other: Travel; Janssen: Honoraria. Renwick:Celgene: Consultancy; Roche: Honoraria. Grigg:MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel. Scott:Medimmune: Consultancy; Abbvie: Consultancy, Patents & Royalties; IBA: Consultancy; Avipep: Consultancy; Life Science Pharmaceuticals: Equity Ownership; Paracrine Therapeutics: Equity Ownership, Patents & Royalties; NHMRC: Research Funding; Cancer Australia: Research Funding; Cancer Council Victoria: Research Funding; Cure Brain Cancer: Research Funding; Humanigen: Patents & Royalties. Lee:Australian Nuclear Science and Technology Organisation: Membership on an entity's Board of Directors or advisory committees. Fong:Astellas: Consultancy; Amgen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Speakers Bureau. Rooney:GenesisCare: Employment. Wight:Janssen: Honoraria; Takeda: Honoraria; Abbvie: Honoraria; BMS: Other: Travel; Amgen: Other: Travel. Chong:BMS: Research Funding; Merck Serono: Research Funding; Bayer: Research Funding; Novartis: Research Funding; Hutchison Medipharma: Research Funding; Pharmacyclics: Research Funding. OffLabel Disclosure: Avelumab is an anti-PDL1 monoclonal antibody.

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Total Metabolic Tumor Volume and Tumor Dissemination Are Independent Prognostic Factors in Advanced Hodgkin Lymphoma

Blood ◽

10.1182/blood-2021-147177 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 880-880

Author(s):

Salim Kanoun ◽

Alina Berriolo-Riedinger ◽

Anne Ségolène Cottereau ◽

Veronique Edeline ◽

Ilan Tal ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Tumor Volume ◽

Metabolic Tumor Volume ◽

Training Set ◽

Advisory Committees ◽

Tumor Dissemination ◽

Ann Arbor ◽

Validation Set

Abstract Background: The AHL2011 study demonstrated that a PET-driven strategy allows to deescalate treatment to 4 x ABVD in PET negative patients after 2 cycles of escalated BEACOPP (BEACOPPesc) without loss of tumor control in patients with advanced Hodgkin lymphoma (HL) compared to a non PET-monitored treatment delivering 6 x BEACOPPesc (Casasnovas RO et al, Lancet Oncol 2019). The interim PET results after 2 (PET2) and 4 (PET4) cycles of chemotherapy were found to influence patients PFS and OS independently of IPS. To further refine the patients outcome prediction we evaluate the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) and tumor dissemination (SDmax) in Ann Arbor stage III-IV patients included in the AHL2011 trial. Patients and methods: 634 patients enrolled in the AHL2011 trial with stage Ann Arbor III or IV were included in the study. According to the AHL2011 trial, patients were randomized in a standard arm (6 x BEACOPPesc) or a PET-driven arm (2 x BEACOPPesc and 4 x ABVD in negative PET2 patients or 4 x BEACOPPesc in positive PET2 patients). For each patient, a semi automatic tumor segmentation was retrospectively performed in baseline PET to calculate TMTV using the 41% of SUVmax threshold and compute the maximum distance between the delineated lesions normalized by body surface area (SDmax). Optimal thresholds for TMTV and SDmax were calculated using X-Tile and ROC curve approaches in a randomly assigned training (n=317) and validation sets (n=317). The per protocol PET2 and PET4 responses were analyzed using the modified Deauville criteria (positive if residual uptake >140% background liver). Multivariate analysis included treatment arm, TMTV, SDmax, international prognosis score (IPS), PET2, and PET4 as covariates. The median follow-up was 5.6y. Results : Median TMTV and SDmax were 215 ml and 0.221 m-1 in the whole population and similar in both randomized arms and in the training and validation sets. Optimal cutoffs were 220ml for TMTV (312 patients [49%] had High TMTV) and 0.330 m-1 for SDmax (149 patients [24%] had High SDmax) and similar in the training and validation sets. 5-year PFS for patients with TMTV>220ml was 84.1% vs 90.2% in low TMTV patients (p=0.02) in the whole population (in the training set: 83% vs 89%, p=0.088 ; in the validation set : 86% vs 92% p=0.11). 5-year PFS was significantly lower in patients with SDmax>0.333 m-1 (78.8% vs 89.7%; HR=2.15 [95%CI: 1.38-3.35], p=0.0005) in the whole population (in the training set: 77% vs 89%; p=0.0037); in the validation set: 81% vs 91; p=0.046). The combination of TMTV and SDmax allows to identify two subgroups of patients, those having both low TMTV and low SDmax (n= 281; 44%) and those having high TMTV and/or SDmax (5-year PFS: 92% vs 83.4%; HR=2.24 [95%CI: 1.39-3.62], p=0.0007) (figure 1). In multivariate analysis, high TMTV (p=0.034), high SDmax (p=0.0002), PET2 (p=0.02) and PET4 (p<0.001) positivity retained independent prognostic value for predicting PFS. Conclusion: Tumor burden (TMTV) and dissemination (SDmax) assessed on baseline 18FDG PET allow to predict, independently of early reponse to treatment, the outcome of patients with advanced HL. These two parameters overcome the prognosis value of IPS and could be included into new prognostic scores to tailor personalized therapy in advanced Hodgkin Lymphoma. Figure 1 : PFS according to TMTV and SDmax in stage III-IV HL patients enrolled in the AHL2011 study Figure 1 Figure 1. Disclosures Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria. Ghesquieres: Janssen: Honoraria; Mundipharma: Consultancy, Honoraria; Roche: Consultancy; Celgene: Consultancy, Honoraria; Gilead Science: Consultancy, Honoraria. Stamatoullas-Bastard: Takeda: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Incyte: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Celgene: Other: Travel/accomodation/expenses; Takeda: Consultancy, Research Funding. Rossi: ROCHE: Honoraria, Research Funding; Takeda: Honoraria; JANSSEN: Honoraria; ABBVIE: Honoraria. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

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Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): High Efficacy of High Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC auto-SCT). A Study of the Lymphoma Working Party (LWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v128.22.514.514 ◽

2016 ◽

Vol 128 (22) ◽

pp. 514-514 ◽

Cited By ~ 1

Author(s):

Saad Akhtar ◽

Silvia Montoto ◽

Ariane Boumendil ◽

Luca Castagna ◽

Herve Finel ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Sufficient Information ◽

Advanced Stage ◽

Advisory Committees ◽

Term Survival ◽

Frequent Relapses ◽

The Impact

Abstract Background: NLPHL is a relatively uncommon subtype of Hodgkin lymphoma (HL) accounting for about 5-6% of all HL cases. It has unique clinico-pathological, morphologic and immunohistochemical features with CD20-positive "lymphocyte predominant cells". Although long-term survival is better than in classical HL, frequent relapses are common and progression/transformation to aggressive non-Hodgkin lymphoma (NHL) may occur. Whilst HDC auto-SCT is considered as standard of care for relapsed/refractory classical HL, data on HDC auto-SCT in relapsed/refractory NLPHL is sparse. Here, we report a registry study of HDC auto-SCT for NLPHL using the EBMT database, representing the largest sample analyzed to date. Design: Eligible were patients with NLPHL18 years or older who underwent a first auto-SCT between 2003 and 2013, and were registered with the EBMT. Patients with NLPHL transformed to DLBCL were not eligible. The primary objective was 5-year progression-free survival (PFS). Baseline patient, disease and transplant data were collected from EBMT MED-A standard forms. Centers with potentially eligible patients were contacted to provide additional treatment and follow-up details with a copy of written diagnostic report for central review. Statistical analysis was descriptive and employed log rank comparisons for univariate assessment of the impact of baseline characteristics on survival endpoints. Results: We identified 92 patients who met the inclusion criteria with full data including a written diagnostic pathology report available. Of these, 36 patients were excluded after histopathology report review (17 classical HL, 2 NHL, 17 no sufficient information). The final sample comprised 56 patients. There was a predominance of male patients with a male:female ratio of 88%:12%. Median age was 36 (interquartile range (IQR) 29-50) years. Most patients (65%) had advanced stage (III-IV) at diagnosis and one third had B-symptoms. Prior to HDC auto-SCT, 71% patients had 2, 20% had 3, and the remainder had more than 3 lines of treatment (median: 2 lines). Rituximab was used in 62% of patients. The median time from diagnosis to HDC auto-SCT was 21 (IQR 14-51) months. Disease status prior to HDC auto-SCT was complete remission (CR) in 54% and partial remission (PR) in 43%. Most commonly used HDC was BEAM (84% patients), with additional rituximab in 13%. With a median follow-up of survivors of 5 (IQR 3.6-6.6) years, 5-year PFS and overall survival were 67% (95%CI 55-82) and 86% (95%CI 77%-96%), respectively. The 5-year incidence of relapse was 32% (95%CI 20-46). There were no transplant-related deaths. Univariate comparisons considering age, time from diagnosis to transplant, number of pre-treatment lines and rituximab use during induction, salvage and/or HDT failed to identify significant predictors of PFS or OS endpoints. Conclusions: This study, the largest reported thus far on HDC auto-SCT in NLPHL, shows that two thirds of patients remain free of disease 5 years after HDC auto-SCT. In contrast with the usual characteristics of patients with NLPHL, those included in this series had high-risk disease with B-symptoms and advanced stage at diagnosis, and half the patients had HDC auto-SCT less than 2 years after diagnosis. This study demonstrates that patients with NLPHL and adverse features can benefit from HDC auto SCT at relapse. Figure. Figure. Disclosures Montoto: Roche: Honoraria; Gilead: Research Funding. Masszi:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Moraleda:Pfizer: Research Funding. Bloor:Janssen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. Meissner:Amgen: Other: Travel Support; Takeda: Other: Travel Support; Celgene: Other: Travel Support; Teva: Other: Travel Support. Dreger:Novartis: Speakers Bureau; Gilead: Consultancy; Gilead: Speakers Bureau; Novartis: Consultancy; Janssen: Consultancy; Roche: Consultancy.

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A Phase II Single Arm Study of Nivolumab As Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression

Blood ◽

10.1182/blood-2021-148139 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2455-2455

Author(s):

Carlos Bachier ◽

Henning Schade ◽

Behyar Zoghi ◽

Aravind Ramakrishnan ◽

Nirav N. Shah

Keyword(s):

Stem Cell ◽

High Risk ◽

Maintenance Therapy ◽

Board Of Directors ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Residual Disease ◽

Refractory Disease ◽

Advisory Committees ◽

Extranodal Disease

Abstract Introduction: Autologous stem cell transplants (ASCT) are standard of care for patients with primary refractory or recurrent Hodgkin lymphoma (HL). While transplant results in cure for some patients, others relapse and succumb from their disease. Studies have found high expression of programmed death ligand 1 (PD-L1) in HL cells. The anti-PD-1 monoclonal antibody, nivolumab, has been safe and efficacious in the treatment of relapsed, refractory HL (Ansell et al. 2015). We evaluated the safety and efficacy of nivolumab maintenance therapy post-ASCT in high risk for relapse Hodgkin disease. Methods: Patients with HL with high risk of residual disease following ASCT ( high risk defined as refractory disease, relapse <12 months, or relapse ≥12 months with extranodal disease after frontline therapy) received nivolumab (240 mg IV every 2 weeks) starting 45-180 days post-transplant for a maximum of 6 months of treatment. Patients were followed for AEs through 100 days after the last dose of drug. PET-CT response assessments were performed 1-3 month, 6 month, and 12 month post-ASCT. The primary objective was to evaluate the safety and tolerability of nivolumab as maintenance therapy early after ASCT. The secondary objective was to evaluate progression-free survival (PFS) at 12 months post-transplant. Results: To date, 37 patients were enrolled; median age 36 years; 25 patients (68%) male. The median number of prior systemic regimens was 2 (range 2-4). 25 patients (68%) had relapsed disease, and 12 patients (32%) had primary refractory disease. 18 patients (49%) had extranodal disease at relapse, 6 patients (16%) had B-symptoms at relapse, and 11 patients (30%) had residual disease after salvage, including 10 patients (27%) of whom had 2-3 prior salvage therapies. 22 patients (60%) had received prior brentuximab, and 3 patients (8%) had received prior nivolumab or pembrolizumab. 36 patients received ASCT and 1 patient received tandem ASCT. At the time of data cutoff, 28 patients (76%) had discontinued nivolumab treatment, 22 patients (60%) because they had completed the 6-month treatment course, 4 patients (11%) due to an adverse event (AE) (1 patient each with pain, pneumonitis, rhabdomyolysis, or hypothyroidism), and 2 patients (5%) due to disease progression. The median duration of treatment was 22.1 weeks. 17 patients (46%) experienced a treatment-related AE (TRAE), of which 5 patients (14%) experienced a ≥Grade 3 TRAE. The most common (≥5%) TRAEs were diarrhea, fatigue, bone pain, neutrophil count decreased, pruritus, rash, and vomiting. 2 patients experienced a treatment-related serious AE (pneumonitis, rhabdomyolysis). There were no treatment-related deaths. With a median follow up of 9.2 months, the median PFS and overall survival (OS) have not been reached. The 6 month PFS is 92.1% and the 12-month OS is 100%. There were no differences in OS when stratified based on prior treatment. Conclusions: The use of nivolumab maintenance early after ASCT is safe and tolerable in this high risk patient population. Early efficacy data is promising, but data need to mature to determine the 12 month PFS. Figure 1 Figure 1. Disclosures Bachier: CRISPR: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Shah: Umoja: Consultancy; Incyte: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy.

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Subcutaneous Alemtuzumab Has Activity in Treatment-Naïve Patients with Acquired Aplastic Anemia

Blood ◽

10.1182/blood-2019-130719 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2503-2503 ◽

Cited By ~ 1

Author(s):

Ana Rita Da Fonseca ◽

Anita Hill ◽

Patricia Eiko Yamakawa ◽

Iara Baldim Rabelo ◽

Andre Domingues Pereira ◽

...

Keyword(s):

Total Dose ◽

Aplastic Anemia ◽

Board Of Directors ◽

Research Funding ◽

Overall Response Rate ◽

Sao Paulo ◽

São Paulo ◽

Advisory Committees ◽

First Line Therapy ◽

Treatment Naïve

Introduction: Hematopoiesis is severely reduced in severe aplastic anemia (SAA) probably due to immunological destruction of hematopoietic stem and progenitor cells. Bone marrow transplantation is preferred as first-line therapy in patients younger than 40 years with a matched related sibling donor. For those who are not candidate for transplant, immunosuppressive therapy with horse antithymocyte globulin (hATG) plus cyclosporine (CsA) remains the standard of care. However, hATG was discontinued in most Asian, South American, and European countries with only rabbit ATG (rATG) available. rATG is a more potent immunosuppressant which has associated with a worst hematological response and survival at 6 months in prospective studies. Using rATG in first-line therapy appears to add little to what has been observed with CSA alone. Alemtuzumab (ALZ), a humanized anti-CD52 monoclonal antibody is also active in AA due to its lymphocytotoxic properties. The use of ALZ in monotherapy has shown an overall response rate (ORR) comparable to that of r-ATG (37% and 33%, respectively) when applied as salvage (following hATG failure) in a randomized study. Other experiences which combined ALZ and CsA led to a 58% ORR in SAA patients after a cumulative dose of 103 mg of subcutaneous (SC) ALZ. Here we describe a multicenter retrospective analysis of SC ALZ in association with CsA for patients with AA. Methods: We retrospectively analyzed all patients who received outpatient SC ALZ for the treatment of aplastic anemia in 2 centers: Universidade Federal de Sao Paulo (Sao Paulo-BRAZIL) and Leeds Teaching Hospitals, UK from March 2009 until March 2019. In Sao Paulo, alemtuzumab total dose was 103 mg in an escalating dose of 3-10-30-30-30 mg, except for three elderly patients who received a total dose of 73. In Leeds-UK, total dose varied from 120 mg to 150 mg. The primary outcome was overall response rate (ORR) at six months. Median follow up was 31 months (range 4-110 months). Results: We identified 35 treatments with SC ALZ in 32 AA patients of which 78% had SAA or very severe aplastic anemia. Calcineurin inhibitors were used in association with ALZ in 80% of cases (cyclosporine in 26 cases, tacrolimus in 2 cases). Median age was 44 years (range: 18-79), and nineteen patients (59%) were male. Seventeen patients (53%) were treatment-naïve, and six patients (19%) had one prior line of therapy. Nine patients (28%) were relapsed/refractory, and received ALZ after at least two lines of prior therapy. Seventeen patients (53%) presented a PNH clone at diagnosis. Median time between diagnosis and ALZ treatment was 6 months (range 1-293). No treatment-related serious adverse events were observed. Infectious complications were infrequent: there was only one case of successfully treated CMV reactivation and one case of fatal EBV-related infection. ORR at 6 months was 57% (complete response: 11%, partial response: 46%), with corresponding cumulative incidence of response of 47% at 6 months and 62% at 1 year (figure 1). ORR was 69% in treatment-naïve patients younger than 60 years. Overall survival was 72% at 2 years. Adverse events were of low grade and infectious events were infrequent. Conclusion: Subcutaneous alemtuzumab appears to be a feasible, effective and safe alternative to hATG in patients with AA requiring immunosuppressive treatment, especially in centers with limited access to hATG. Disclosures Hill: Apellis: Honoraria; Roche: Honoraria; Akari: Honoraria; Alexion: Honoraria; Bioverativ: Honoraria; Novartis: Honoraria; Regeneron: Honoraria; Ra Pharma: Honoraria. Munir:AbbVie: Honoraria; Alexion: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sunesis: Consultancy; Pharmacyclics: Other: TBC; Acerta: Membership on an entity's Board of Directors or advisory committees. Hillmen:Roche: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Apellis: Research Funding; Gilead: Research Funding. Risitano:Achillion: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Biocryst: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; Ra Pharma: Research Funding; Alnylam: Research Funding; Achillion: Research Funding; Alexion: Honoraria, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; Ra Pharma: Research Funding; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Research Funding, Speakers Bureau. Scheinberg:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer,: Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau.

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Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Blood ◽

10.1182/blood-2019-122393 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2898-2898

Author(s):

Vania Phuoc ◽

Leidy Isenalumhe ◽

Hayder Saeed ◽

Celeste Bello ◽

Bijal Shah ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Fdg Pet ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Advisory Committees ◽

End Of Treatment

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p<0.0001), IHP (Χ2=49.078, p<0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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Carfilzomib Thalidomide and Dexamethasone Is Safe and Effective in the Treatment of Relapsed/Refractory Multiple Myeloma: An Open Label Phase II Australasian Leukaemia and Lymphoma Group (ALLG) MM 018/ Asian Myeloma Network (AMN) 002 Study

Blood ◽

10.1182/blood-2020-139174 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Hang Quach ◽

Simon J Harrison ◽

Je-Jung Lee ◽

Nichloas Murphy ◽

Jae Hoon Lee ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Board Of Directors ◽

Phase Ii ◽

Primary Endpoint ◽

Research Funding ◽

Open Label ◽

Advisory Committees ◽

Open Label Phase ◽

Grade 3

Background: The combination of carfilzomib with immunomodulatory drugs (IMiDs) and dexamethasone is active in multiple myeloma (MM). Carfilzomib, thalidomide, and dexamethasone (KTd) has been studied in upfront MM treatment but has not been studied in the setting of relapsed/refractory myeloma (RRMM). The ALLG MM018/ AMN002 is an open-label phase II study of KTd in patients with RRMM. This study was conducted across 16 sites across Australia, New-Zealand, Singapore, South Korea and Taiwan. Method: Patients with RRMM with 1-3 prior lines of treatment were given carfilzomib [K: 20mg/m2 IV cycle 1 days 1 and 2, 56mg/m2 (36mg/m2 for patients age ≥75 years) from cycle 1 day 8 onwards], thalidomide (T: 100mg po nocte) and dexamethasone [dex: 40mg (20mg for patients age ≥75 years) po weekly], in a 28-day cycle. After 12 cycles, T was omitted, and K was given on days 1,2,15,16 and dex days 1,15 every 28-day cycles for a further six cycles. The primary endpoint was PFS. Secondary endpoints were ORR, overall survival, adverse events, and quality of life (QoL). The study had an 80% power to detect a ≥70% PFS at 6.5 months compared to historical ≤50% PFS at 6.5 months expected with Td (Kropff, M. et al. Haematologica 2012), at a significance level of 0.05. Results: This study has completed accrual. Eighty-three patients [median age of 66 years (42-85)] were enrolled with a median follow up of 15.9 (0.9-26) months. ORR rates were 86.4% (≥VGPR 70.2%). Median PFS was 20m (95% CI 15.9-26m). PFS at 6.5 months was 76.2% (95% CI 73.6-84.9%). Median OS has not been reached, and was 75% at 20 months. The most common grade ≥3/4 AEs were peripheral neuropathy (16%), upper respiratory tract infections (12%), dyspnoea (14%), and hypertension (10%). Grade ≥3/4 cardiac AEs occurred in 6%. The median carfilzomib dose that was delivered was 70.7% (32.8-92.6%) of the target dose. Thus far, 41% of patients have completed the intended 18 cycles of treatment. 21% of patients ceased therapy early. The most common reason for early treatment cessation was disease progression (30%) and adverse events (15%). Fifteen patients (18%) have died, 11 were due to MM, two from infection, one from an ischaemic cardiac event, and one from a traffic accident. QoL, as measured by the EQ-5D-5L instrument, remained stable throughout treatment. Conclusion: The ALLG MM018/AMN 002 study has met its primary endpoint. The KTd schedule as outlined in this study is efficacious in patients with RRMM, resulting in a prolonged PFS and a safety profile in line with previous reports for each of carfilzomib and thalidomide. KTd is an active option in jurisdictions where the cost of other IMiDs prohibits regulatory funding. Comparisons of efficacy and adverse events between the Caucasian and Asian populations will be presented at the meeting. Disclosures Quach: Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Sanofi: Consultancy, Research Funding. Harrison:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; Haemalogix: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Campbell:Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding; AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Soo:Hanmi: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

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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.

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