Efficacy of HMA +/- Venetoclax or Intensive Chemotherapy in Blast-Phase Myeloproliferative Neoplasms

Abstract Introduction Blast-phase (BP), or leukemic transformation is a rare and devastating complication of myeloproliferative neoplasms (MPNs) (primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET), and post-PV/ET myelofibrosis). Patients with BP-MPNs have a poor prognosis with a median overall survival of less than 6 months, and there is no standard treatment regimen for these aggressive diseases (Dunbar et al, Blood. 2020). The development of hypomethylating agent (HMA)/venetoclax (Ven) combination offers new hope for some with AML, but has been relatively disappointing in BP-MPN, though data are limited and retrospective (Masarova et al, Blood Adv. 2021; Gangat et al, Am J Hematol. 2021). Here, we add our experience with several common treatment regimens for BP-MPN. Methods We retrospectively analyzed data from 39 consecutive patients with BP-MPNs diagnosed from December 2008 to February 2021 who received treatment at the University of Michigan. We included all patients with a previous diagnosis of MPNs who had ≥ 20% blasts in the peripheral blood or bone marrow, and subsequently received systemic therapy. One patient with a myeloid sarcoma was included as well. Disease characteristics at time of BP-transformation were noted. Patients were divided into the following groups based on 1 st-line induction therapy: 7+3 (daunorubicin and cytarabine), FLAG (fludarabine, high-dose cytarabine and G-CSF), hypomethylating agent only (decitabine or azacitidine), and HMA/Ven. Patients were followed for 2 years post-diagnosis. Differences in induction response were assessed using the Chi-square test. Differences in overall survival were calculated using the Kaplan-Meier regression with the log-rank test. Two patients who received alternate induction therapy outside of the four groups were not included in these analyses. Results The composite BP-MPN population had a median advanced age of 69 years old and a median ECOG performance status (PS) of 1. Most (97.4%) had received systemic treatment prior to their transformation for their MPN, with 71.8% receiving hydroxyurea and 41.0% receiving ruxolitinib. The rate of response (CR, CRi, MLFS) was highest in the HMA/Ven group at 42.9%, followed by FLAG (29.4%), HMA only (11.1%), and 7+3 (0%), p = 0.033 (Table 3). Despite the higher response rate, differences in 2-year OS were not significantly different among the 4 groups: 7+3 (25.0%), FLAG (7.7%), HMA (0%), HMA/Ven (20.0%) (p=0.92, Figure 1). Median time to relapse after achieving remission ranged from 2-10 months, and did not vary significantly based on induction regimen. Patients in the HMA and HMA/Ven groups had higher incidences of death with induction at 77.8% and 28.6%, respectively (Table 3). Conclusions The highest rates of response, including complete remission, were achieved with the combination of HMA and venetoclax compared to intensive induction chemotherapy or HMA alone. However, this did not translate into significant differences in OS, which is consistent with other retrospective reports. No responses were seen with 7+3 induction, though several patients were able to go on salvaged with other therapies and subsequent allogeneic stem cell transplantation thereafter. Finally, the baseline poor ECOG PS of the HMA group and borderline ECOG PS of the HMA/Ven group also contribute to their low survival rates.Larger, prospective studies comparing currently available treatment regimens in BP-MPN would be helpful, but ultimately new therapies are desperately needed for this high-risk disease. Figure 1 Figure 1. Disclosures Bixby: Takeda: Consultancy. Talpaz: Constellation: 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; Takeda: Other: Grant/research support ; Celgene: Consultancy; Imago: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Different Treatment Approaches to Blast Phase-Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2021-146945 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3641-3641

Author(s):

Franco Castillo Tokumori ◽

Najla Al Ali ◽

Onyee Chan ◽

David A. Sallman ◽

Seongseok Yun ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Initial Treatment ◽

Research Funding ◽

Clinical Characteristics ◽

Myeloproliferative Neoplasms ◽

Intensive Chemotherapy ◽

Blast Phase ◽

Advisory Committees

Abstract CONTEXT: Transformation to acute myeloid leukemia (AML) occurs in 5-20% of patients with myeloproliferative neoplasms (MPN). Overall survival in blast phase MPN (MPN-BP) is poor, usually in the range of 3 to 6 months, and is not significantly impacted by intensive chemotherapy. Current guidelines favor treatment with a hypomethylating agent (HMA), but survival remains poor, and allogeneic hematopoietic stem cell transplantation (AHSCT) holds the only potential for long term survival. OBJECTIVE: To describe the clinical characteristics and overall survival of MPN-BP according to different treatment approaches. DESIGN: Single-institution, retrospective analysis of 70 MPN patients that progressed to blast phase, who presented to our institution between 2001 and 2020. Transformation to AML defined as >20% myeloblasts in peripheral blood or bone marrow. We stratified the patients according to initial treatment strategy for AML. Baseline variables were compared between groups. Median overall survival (mOS) was measured from time of AML diagnosis to date of death. Kaplan-Meier plots were created to compare mOS. RESULTS: Among 70 MF patients that progressed to AML, initial treatment was: 19 best supportive care (BSC), 25 HMA (20 HMA only and 5 HMA + venetoclax), and 26 intensive chemotherapy (IC) [12 patients received standard "7+3" regimen with daunorubicin/idarubicin and cytarabine, 12 received high-dose cytarabine, cladribine +/- mitoxantrone (CLAG/CLAG-M), and 2 received CPX-351 (Vyxeos)]. Patients receiving IC were younger at time of leukemic transformation than those receiving BSC (median 63.9 years vs 72.9 years; p=0.029) or HMA (median 63.9 years vs. 69.0 years; p=0.026). Additionally, 70% of IC patients had an ECOG performance status of 0 or 1 compared to just 48% of patients receiving either BSC or HMA (p=0.088). Median OS for the entire cohort (n = 70) was 4.8 months. Compared to patients who received active treatment with HMA or IC, those treated with BSC had shorter survival (0.9 months vs 6.4 months; p=0.001). Median survival between patients treated with HMA and IC was not significantly different (4.5 months vs 9.6 months; p=0.13). Patients treated with IC were more likely to proceed to AHSCT (46% vs 5%; p < 0.001). Between HMA and IC groups, there was no difference in time from MPN-BP diagnosis to treatment (median 0.4 months vs 0.3 months; p=0.644) or total number of lines of treatment for MPN-BP. Focusing specifically on the role of AHSCT in patients treated with IC, we found that patients who received AHSCT had significantly longer mOS than those patients who did not (18.9 months vs 4.9 months; p=0.002), suggesting the beneficial role of intensive chemotherapy is critically tied to the ability to subsequently undergo AHSCT. Among patients who underwent AHSCT, 1-year and 2-year OS was 51% and 34%, respectively. In contrast, patients not receiving AHSCT had 1-year and 2-year OS of 14% and 2%, respectively. Independent of age, AHSCT (p=0.008) and receipt of therapy (p=0.017) significantly correlated with longer survival after AML diagnosis. Besides these factors, there were no significant differences in the clinical characteristics between the three groups. Acknowledging the limitations associated with small numbers, we did not note any difference in survival between patients who received HMA vs HMA + venetoclax (p=0.27). CONCLUSIONS: In MPN-BP, patients receiving treatment had superior outcomes to those that received BSC. Initial treatment with intensive chemotherapy was associated with non-significant improvement in survival; however, this appears to be critically linked to the receipt of AHSCT. In appropriate patients, intensive chemotherapy may be reasonable in an effort to provide an effective bridge to AHSCT. Still, this study reinforces the poor prognosis associated with MPN-BP and the desperate need for novel therapeutic approaches in this group of patients. Figure 1 Figure 1. Disclosures Sallman: AbbVie: Membership on an entity's Board of Directors or advisory committees; Magenta: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: 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, Speakers Bureau; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Sweet: Bristol Meyers 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; AROG: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Padron: BMS: Research Funding; Kura: Research Funding; Incyte: Research Funding; Blueprint: Honoraria; Taiho: Honoraria; Stemline: Honoraria. Lancet: Daiichi Sankyo: Consultancy; Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; BerGenBio: Consultancy; AbbVie: Consultancy; Astellas: Consultancy; Agios: Consultancy; ElevateBio Management: Consultancy; Jazz: Consultancy. Komrokji: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Acceleron: Consultancy; Jazz: Consultancy, Speakers Bureau; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Kuykendall: Novartis: Honoraria, Speakers Bureau; Prelude: Research Funding; Incyte: Consultancy; PharmaEssentia: Honoraria; CTI Biopharma: Honoraria; Celgene/BMS: Honoraria, Speakers Bureau; BluePrint Medicines: Honoraria, Speakers Bureau; Abbvie: Honoraria; Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Characteristics Of Multiple Myeloma Patients With 6-Year Or Longer Progression-Free Survival After a Single Autologous Transplant

Blood ◽

10.1182/blood.v122.21.3366.3366 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3366-3366 ◽

Cited By ~ 2

Author(s):

Kehinde U.A. Adekola ◽

Qaiser Bashir ◽

Nina Shah ◽

Sai Ravi Pingali ◽

Simrit Parmar ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Induction Therapy ◽

Progression Free Survival ◽

High Dose ◽

Cell Transplant ◽

Advisory Committees ◽

Free Survival ◽

Autologous Transplant ◽

Preparative Regimen

Background High dose chemotherapy followed by an autologous stem cell transplant (auto-HCT) is considered standard of care in patients with newly diagnosed multiple myeloma (MM). In a recent randomized trial, median progression free survival (PFS) after auto-HCT, with or without maintenance therapy was 46 and 27 months, respectively (McCarthy P et al. NEJM 2012). However, about 15% of patients are reported to have much longer PFS (Pineda-Roman M et al. Cancer 2008). Here we tried to identify the factors that may predict a long PFS after auto-HCT. Methods We performed a retrospective chart review of patients who received an auto-HCT for MM between January 2000 and March 2007. A total of 1135 patients underwent an auto-HCT during this period, and 194 patients (17%) had a minimum PFS of 72 months or longer after a single auto-HCT. The primary objective was to determine the variables associated with a long PFS and overall survival (OS). Results Patient characteristics and outcomes are shown in the attached Table. The median age at auto-HCT was 56 years, and the median time from diagnosis to auto-HCT was 7.5 months. Twenty-three (13%) patients had ≥ 10% plasma cells in the bone marrow at auto-HCT and only 9 patients (4.8%) had high-risk cytogenetic abnormalities. One-hundred and fifty (77%) patients received induction therapy containing either an immunomodulatory (IMiD) agent or a proteasome inhibitor (PI). At the time of the auto-HSCT, only 13 (6.7%) patients were in CR and 38 (19.6%) were CR or VGPR after induction therapy (Table). One-hundred and sixty three (84%) patients received mephalan alone as conditioning regimen. Eighty-one (42%) patients received post auto-HCT maintenance. Eighty (41%) patients achieved a CR, while 104 (54%) achieved CR + VGPR after auto-HCT. Six patients (3.1%) developed a second primary malignancy post- autologous transplant. After a median follow-up of 95.4 months, median PFS was 97.3 months and median OS has not been reached. The 10-year PFS and OS were 41% and 73% respectively. Use of melphalan alone as preparative regimen was associated with a longer PFS and OS (p=0.004 and 0.004, respectively). Achievement of CR after auto-HCT was associated with a longer PFS only (p=0.001), and the use of IMiD or a PI as induction was associated with a longer OS (p=0.01). Conclusion Approximately 17% patients achieved a median PFS of 6 years or longer after a single auto-HCT. The long PFS in this cohort may be associated with younger age, low incidence of HR cytogenetics, use of an IMiD or PI as induction therapy, relatively low disease burden at auto-HCT, transplant from the year 2000 onwards, achievement of CR in >40% and the use of melphalan alone as preparative regimen. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees.

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Systematic Reviews of the Clinical Efficacy and Safety of First-Line Treatments for Patients with Mantle Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-118685 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5868-5868

Author(s):

Neerav Monga ◽

Jamie Garside ◽

Matthew S. Davids ◽

Constantine S. Tam ◽

Katherine Ward ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

Eligible Patient ◽

High Dose ◽

Efficacy And Safety ◽

First Line ◽

Advisory Committees ◽

Treatment Regimens ◽

Mantle Cell

Abstract Introduction Mantle cell lymphoma (MCL) is a rare and aggressive form of Non-Hodgkin's lymphoma (NHL) with poor survival outcomes. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is recommended as first-line therapy in younger patients. However the comparative efficacy of such regimens, and of alternative therapy options (for patients unable to tolerate chemotherapy + ASCT), remain unclear. A comprehensive understanding of the current evidence is therefore required. Methods Two systematic reviews (SRs) were developed to identify efficacy and safety data for therapies used in the first-line treatment of MCL. One review identified randomised controlled trials (RCTs) and the other non-randomised studies (NRSs). Searches were carried out in EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Clinical Trials electronic databases. Additionally, conference materials were screened from ASH, EHA, ESMO and ASCO proceedings from the last 2 years. All review methodologies were performed according to Cochrane best practice guidelines Results The RCT SR was run in August 2017 and updated in April 2018. Overall, 2,787 abstracts were screened. The SR included 9 full-text articles and data from 2 conference proceedings, together reporting a total of 7 independent studies. Across the RCTs, the most commonly investigated treatment regimens were rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone (R-CHOP), and bendamustine + rituximab (BR). Frequently reported primary endpoints were response rates and progression-free survival (PFS). Table 1 presents the PFS and overall survival (OS) data reported in the included RCTs. Data from the RCT reporting on intensive induction chemotherapy followed by ASCT are separated from regimens that did not include ASCT. There were notable differences in median PFS rates, between both patients receiving ASCT versus patients not receiving ASCT and also between the two ASCT treatment arms. In pharmacotherapy studies, PFS ranged from 14.4 to 35.4 months, whereas the two arms of the ASCT RCT reported 51.6 and 109.2 months, respectively. Similar trends were observed in OS: the only result for patients undergoing ASCT (117.6 months) was higher than any result reported in patients not receiving transplant (range 40 - 60 months). However, study heterogeneity may affect the appropriateness of directly comparing these results. Frequently reported grade 3-4 adverse events included anemia, infusion-related reactions, nausea, neutropenia and thrombocytopenia (four of seven RCTs reported each event). The NRS SR was run in April 2018. A total of 3,290 abstracts were screened and 75 full papers were assessed. The SR included 25 full-text articles and 6 conference proceedings, together reporting a total of 18 independent single-arm studies. Several of the NRSs investigated treatment regimens that have not been described in RCT studies, including: R-CHOP with alternating or sequential rituximab + cytarabine (maxiCHOP), and cyclophosphamide + vincristine + doxorubicin + dexamethasone alternating with high dose methotrexate or cytarabine + rituximab (hyperCVAD + R). Across the NRSs, the longest median PFS was 8.5 years (102 months), in patients treated with maxiCHOP (who were young/ASCT-eligible patients). This outcome was reported in a patient population who had responded to induction therapy and were treated with consolidative ASCT. Across all studies there was heterogeneity in the eligible patient population, with some studies focusing on unfit patients and others focusing on high-dose-therapy-eligible patient populations. Many studies also reported maintenance or consolidation treatments, which would influence the long-term outcomes of the patients. Conclusions These SRs highlight the paucity of directly comparable evidence on the efficacy and safety of therapies for patients with MCL. Although there are some marked differences in patient outcomes according to therapy regimen, considerable heterogeneity in study design and patient populations make direct comparison difficult. Despite this, these SRs highlight that MCL remains a difficult subtype of NHL to treat, with short survival highlighting the high unmet need. With new and emerging therapies, additional research is essential to understand optimal regimens for first-line MCL. Table 1. Table 1. Disclosures Monga: Janssen Pharmaceutica NV: Employment. Garside:Janssen Pharmaceutica NV: Employment. Davids:Merck: Consultancy; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Research Funding; BMS: Research Funding; Surface Oncology: Research Funding; Celgene: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Tam:BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ward:Janssen Pharmaceutica NV: Consultancy. Quigley:Janssen Pharmaceutica NV: Consultancy. Parisi:Janssen: Employment. Tapprich:Janssen Pharmaceutica NV: Employment.

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Induction Therapy with Everolimus in Combination with DHAP (Dexamethasone, High-Dose AraC, Cisplatinum) in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma: A Randomized, Placebo-Controlled Phase I/II Trial (HD-R3i)

Blood ◽

10.1182/blood-2018-99-117291 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2912-2912 ◽

Cited By ~ 1

Author(s):

Bastian von Tresckow ◽

Andreas Hüttmann ◽

Vladan Vucinic ◽

Horst Mueller ◽

Annette Plütschow ◽

...

Keyword(s):

Placebo Group ◽

Phase I ◽

Board Of Directors ◽

Phase Ii ◽

Induction Therapy ◽

Research Funding ◽

High Dose ◽

Classical Hodgkin Lymphoma ◽

Advisory Committees ◽

Support Research

Abstract Introduction: Induction chemotherapy followed by BEAM high dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSC transplant) is standard of care for transplant-eligible patients with relapsed or refractory classical Hodgkin lymphoma (rrHL). However, approx. 50% of patients relapse and therefore, this strategy must be improved. As response to induction therapy is predictive of the outcome after HDCT, this trial aimed at improving the response to induction therapy by adding oral everolimus to time-intensified standard DHAP (Ever-DHAP). Methods: We included patients with histologically confirmed rrHL aged 18-60 years in this phase I/II trial. Dosage of everolimus was pre-determined in the phase I part with 10 mg/day given parallel to DHAP for 14 days within each of two cycles. The phase II part started as a randomized controlled trial comparing 50 patients in the everolimus group to 50 patients in a placebo group. The primary endpoint of the phase II part was the CT-based complete remission (CR-) rate after two cycles of Ever-DHAP. This CR-rate would be expected to be ≥ 40% if adding everolimus was effective. Secondary efficacy endpoints of the trial were PET-based CR-rate after two cycles of induction, progression-free and overall survival. Secondary feasibility endpoints were time to recovery, CTC-based adverse events, duration of induction therapy, discontinuation rates and the rates of successful PBSC collection. The trial was registered at ClinicalTrials.gov with ID NCT01453504. Results: From 7/2014 to 3/2018 we recruited a total of 59 patients in the phase II part. Because of poor recruitment the placebo group was closed in 9/2015 after 9 patients were randomized. These patients are analyzed in a descriptive way only. Of 50 patients in the everolimus group two were not evaluable because of retracting consent and not starting therapy; three additional patients discontinued Ever-DHAP because of toxicity. PBSC collection was successful in 37/39 documented patients receiving Ever-DHAP (95%). After two cycles of therapy we observed a CT-based CR in 12/45 patients of the everolimus group (27%) and in 2/9 patients of the placebo group (22%). A PET-based CR was achieved by 19/38 patients of the everolimus group (50%) and by 4/5 patients of the placebo group. In the everolimus group two patients had refractory disease (4%) and two died (4%), 3 and 4 months after starting but not related to Ever-DHAP. Final results and additional analyses will be presented. Conclusions: Adding everolimus to time-intensified DHAP is feasible, however, the Ever-DHAP regimen failed to show an improved efficacy. Disclosures von Tresckow: Novartis: Honoraria, Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; MSD: Honoraria, Other: Travel support, Research Funding. Hüttmann:Celgene: Other: Travel expenses; Roche: Other: Travel expenses. Viardot:Amgen: Consultancy; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Gilead Kite: Consultancy, Honoraria. Topp:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding. Borchmann:Novartis: Consultancy, Honoraria.

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Real World Outcomes of Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation and Receive Commercially-Available Salvage Therapy

Blood ◽

10.1182/blood-2019-128815 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2893-2893

Author(s):

Emily C. Ayers ◽

David J Margolis ◽

Phyllis A. Gimotty ◽

Daniel J. Landsburg

Keyword(s):

Board Of Directors ◽

Research Funding ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Current Therapy ◽

High Dose ◽

Cell Of Origin ◽

Advisory Committees ◽

Ecog Ps

Introduction: Salvage immunochemotherapy (IC) followed by high-dose chemotherapy with autologous stem cell transplantation (autoSCT) is standard-of-care second-line therapy (2L) for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) deemed fit for autoSCT as per the CORAL study (J Clin Oncol. 2010 Sep 20;28(27):4184-90). Optimal therapeutic management of patients with R/R DLBCL who are autoSCT-ineligible is unknown. Here we describe the real-world outcomes of patients with R/R DLBCL who receive palliative intent 2L therapy in community and academic settings and do not receive autoSCT. Methods: This analysis includes de-identified patients from the nationwide Flatiron Health electronic health record-derived database with a histologic diagnosis of DLBCL and R/R disease after frontline IC who do not undergo autoSCT and receive treatment with either bendamustine-based therapy, gemcitabine-based therapy, lenalidomide, or ibrutinib. Patients receiving rituximab/ifosfamide/carboplatin/etoposide (R-ICE) and high-dose cytarabine-containing second-line therapies were excluded. Event free survival (EFS) was defined as the interval between the start of current therapy and start of subsequent therapy if needed, last follow-up on current therapy, or death on therapy. Overall survival (OS) was defined as the time between start of current therapy and death or last follow-up while alive. Results: A total of 250 patients were eligible for inclusion in 2L. Eight patients received autoSCT after gemcitabine therapy and were excluded from this analysis. Clinicopathologic characteristics at time of diagnosis include 56% male, 87% age >60, 55% ECOG performance status >1, 87% stage III-IV disease, 78% IPI >2, 56% germinal center (GCB) of those with cell of origin testing performed, 9% cMYC rearrangement positive when tested, and 29% transformed from indolent disease. A total of 106, 78, 36, and 22 patients received bendamustine, gemcitabine, lenalidomide, and ibrutinib, respectively. For all patients, median EFS was 5.1 months and median OS was 14.3 months in 2L. Median EFS was 7.6, 2.4, 9.1, and 4.2 months, and median OS was 16.0, 9.4, 16.3, and 11 months for bendamustine, gemcitabine, lenalidomide, and ibrutinib in 2L, respectively. Patients receiving bendamustine and lenalidomide demonstrated significantly improved EFS compared to those receiving gemcitabine (p=0.001 and 0.01, respectively), see Figure 1. We observed no difference in EFS (p=0.40) or OS (p=0.89) between lenalidomide and bendamustine in 2L. Univariate analysis demonstrated receipt of gemcitabine, ECOG PS>1, and IPI >2 to have statistically significant increased hazard for treatment failure and ECOG PS>1 to have an increased hazard for death in 2L relative to the reference group. Multivariate analysis demonstrated receipt of gemcitabine (HR 1.57, p=0.03 95% CI: 1.04 - 2.37) and ECOG PS>1 (HR 1.61, p=0.02 95% CI: 1.09-2.38) were associated with an increased hazard for treatment failure in 2L. Median EFS for patients on lenalidomide was 6.7 and 8 months (p=0.26), and median OS was 13.9 and 12.2 months (p =0.48) for patients with nonGCB and GCB cell of origin, respectively. Conclusions: For patients with R/R DLBCL treated with palliative therapy in the 2L, bendamustine- and lenalidomide-based therapies resulted in significantly longer EFS compared to gemcitabine therapy. Although we cannot exclude the possibility that some patients received gemcitabine in 2L with the original intent to proceed with autoSCT, this does not contest our results as this therapy remains inferior to bendamustine and lenalidomide even if given to a potentially more fit patient population. Analysis shows no difference in outcomes by cell of origin if receiving lenalidomide in 2L. These findings may serve as benchmarks for outcomes following receipt of these therapies in the non-investigational setting and suggest both bendamustine and lenalidomide may be considered reasonable standard-of-care therapies for patients unfit for autoSCT in the 2L setting. Figure 1 Disclosures Landsburg: Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding. OffLabel Disclosure: Outcomes with lenalidomide and ibrutinib in patients with relapsed/refractory DLBCL will be discussed.

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Clinico-Molecular Features and Treatment Outcomes in Primary Myelofibrosis Phenotypes with Protracted Disease Dynamics

Blood ◽

10.1182/blood-2021-152026 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2571-2571

Author(s):

Luis E. Aguirre ◽

Akriti G Jain ◽

Somedeb Ball ◽

Najla Al Ali ◽

Sara Marie Tinsley-Vance ◽

...

Keyword(s):

Board Of Directors ◽

Active Surveillance ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Lower Percentage ◽

Cancer Center ◽

Blast Phase ◽

Advisory Committees ◽

Molecular Features

Abstract Background Primary myelofibrosis (PMF) is the most aggressive subtype among classical BCR-ABL1 negative myeloproliferative neoplasms (MPN). Driven by constitutive activation of the JAK/STAT pathway, its prognosis is defined by cardinal clinical, cytogenetic and molecular features. While most patients require therapy for symptomatic splenomegaly, disease-related symptoms, or cytopenias, asymptomatic lower-risk patients may be appropriately monitored with active surveillance. The aim of this study was to explore disease characteristics and outcomes among pts who remained on prolonged active surveillance compared to those who received early treatment. Methods We identified patients with confirmed MF (inclusive of primary MF and MF occurring after essential thrombocythemia or polycythemia vera) treated at Moffitt Cancer Center between 2003-2021. Patients were stratified into two cohorts: those remaining on active surveillance for ≥ 36 months following diagnosis and those who received within 36 months of diagnosis. Results Between August 2000 and March 2021, we identified 626 patients with a diagnosis of MF. Among these, 48 (8%) did not receive treatment for at least 3 years. Table 1 summarizes the baseline characteristics comparing those pts who remained on active surveillance for ≥ 36 months (LTO-MF) to those who received treatment within 36 months of diagnosis (ET-MF). The LTO cohort presented at a younger age (median age 63 vs 68; p = 0.001), but otherwise demographic variables were balanced between the two cohorts. LTO patients were more likely to have primary MF (85.4% vs 60.9%, p=0.003). LTO patients were less likely to have leukocytosis (28.2% vs 49.9%, p=0.01), and constitutional symptoms (29.8% vs 44.6%, p=0.05), while having a higher reticulocyte percentage (81.4% vs 64.1%, p=0.02). LTO patients also had lower platelet counts (mean: 274k vs 359k, p=0.006), lower percentage of circulating blasts (0.4% vs 1.2%, p<0.001), and lower percentage of marrow myeloblasts (1.3% vs 1.9%, p<0.001) at baseline. Cohorts had comparable rates of anemia, thrombocytopenia, transfusion dependence, LDH levels and splenomegaly at baseline. Interestingly, the cohorts were well-balanced in terms of risk score based across all major prognostic scoring systems: IPSS (p=0.356), DIPSS (p=0.764), DIPSS+ (p=0.148), GIPSS (p=0.125), MIPSS70 (p=0.924) and MIPSS70+ (p=0.407). There was no association between GPSS karyotype risk and need to start treatment earlier (p=0.481) (Table 1). LTO patients were less likely to harbor JAK2 mutations (58.3% vs 72.4%, p=0.04). No significant differences were seen regarding CALR (p=0.144), MPL (p= 0.271), or triple-negative disease (p=0.521) (Table 2). The median OS (mOS) for the entire population was 82.5 months (95%CI 69.4-95.5). LTO patients had longer OS (mOS 170.3 mo vs 63.9 mo; (p<0.001). Rates of transformation to blast phase were comparable (6.2% vs 9.7%;p=0.441), but median time to blast phase transformation was longer for LTO MF: 66.3 mo vs 29 mo, p=0.011). Expectedly, time to first treatment longer for LTO patients (62.1 mo vs 0.9 mo; (p<0.001). No differences were noted between cohorts in terms of response to ruxolitinib, duration of response to ruxolitinib or response to lenalidomide/thalidomide (p = 0.91, 0.90, 0.83, respectively) Conclusion In this single-center study of patients seen at a tertiary referral center, the vast majority of MF patient required treatment within 36 months of diagnosis. Those monitored with active surveillance were younger, had less proliferative signs/symptoms, were less likely to have JAK2 mutations, and more favorable outcomes. Figure 1 Figure 1. Disclosures Tinsley-Vance: Fresenius Kabi: Consultancy; Novartis: Consultancy; Incyte: Consultancy, Speakers Bureau; Abbvie: Honoraria; Jazz: Consultancy, Speakers Bureau; Taiho: Consultancy; Celgene/BMS: Consultancy, Speakers Bureau; Astellas: Speakers Bureau. Sallman: Magenta: Consultancy; Takeda: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: 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, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees. Lancet: AbbVie: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Celgene/BMS: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Millenium Pharma/Takeda: Consultancy; Jazz: Consultancy. Padron: Incyte: Research Funding; BMS: Research Funding; Taiho: Honoraria; Kura: Research Funding; Blueprint: Honoraria; Stemline: Honoraria. Kuykendall: Novartis: Honoraria, Speakers Bureau; Incyte: Consultancy; BluePrint Medicines: Honoraria, Speakers Bureau; Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Research Funding; PharmaEssentia: Honoraria; Abbvie: Honoraria; Celgene/BMS: Honoraria, Speakers Bureau; CTI Biopharma: Honoraria. Komrokji: AbbVie: Consultancy; Geron: Consultancy; Acceleron: Consultancy; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees.

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Overall Survival in Patients with JAK2 and ASXL1 Positive Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2019-128309 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5383-5383

Author(s):

Murtadha Al-Khabori ◽

Shoaib Al-Zadjali ◽

Iman Al Noumani ◽

Khalil Al Farsi ◽

Salam Al-Kindi ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Myeloproliferative Neoplasms ◽

Prognostic Significance ◽

Jak2 V617f ◽

World Health ◽

Prognostic Impact ◽

Advisory Committees ◽

Myeloid Neoplasms ◽

The Impact

Objectives: Mutations in additional sex combs-like transcriptional regulator 1 (ASXL1) have been previously described in myeloid neoplasms (21% in non-Myeloproliferative [MPN; Tefferi A, Leukemia, 2010) and have been associated with a more aggressive disease [Rocquain J et al, BMC Cacer, 2010]. They can also be found in patients with JAK2 positive MPN [Abdel-Wahab O et al, Cancer Research, 2010). Disruption of ASXL1 gene leads to MPN phenotype in zebrafish model (Gjini E, Dis Model Mech, 2019). The co-expression and the prognostic significance of ASXL1 in patients with JAK2 positive MPN are not yet fully defined. We therefore planned to define the prognostic impact of ASXL1 mutations on the Overall Survival (OS) of patients with JAK2 positive MPN. Methods: We included patients with JAK2 V617F positive MPN diagnosed according to the World Health Organization 2016 criteria and treated at the three largest hematology centers in Oman. The entire coding region of ASXL1 gene was sequenced using Next Generation Sequencing (NGS; Ion PGM Sequencer; Thermo Fisher Scientific®). The library was constructed and the templates were prepared using the PGM tool and the variants were annotated using the ClinVar database and the prediction from the Scale-Invariant Feature Transform (SIFT) and or Polymorphism Phenotyping (Polyphen) algorithms. The NGS analysis was done on the frozen diagnostic bone marrow samples. The survival probability was estimated using Kaplan-Meier estimator and Cox regression was used to assess the impact of predictors on the OS outcome. An alpha threshold of 0.05 was used. The R program (version 3.1.2) was used for all statistical analyses. Results: A total of 58 patients with JAK2 V617F positive MPN were included. All of these patients were found to have mutated ASXL1 using the NGS (ASXL1 p.Leu815Pro was found in all patients). The median age of this cohort was 62 years (InterQuartile Range [IQR]: 44 - 70) and female to male ratio was 25:33. The median hemoglobin, hematocrit, white blood cell count and platelet count was 14.7 g/dL, 58%, 11.5 x109/L and 518 x109/L respectively. Out of the 58 patients included, 28 had polycythemia vera, 20 had essential thrombocythemia, 8 had myelofibrosis and 2 had MPN-Unclassified. The median time from diagnosis to last follow up or death was 13 months (IQR: 3-39). During this period, 5 patients died. The probability of OS at 3 years was 88%. The median OS was not reached. In the univariable analysis, age was a statistically significant predictor of OS (p = 0.0355) but not gender (p = 0.434) and MPN subtype (p = 0.7). In the multivariable analysis model of the previous three factors, age remained statistically significant (Hazard ratio = 1.13, p = 0.041). Conclusions: ASXL1 is mutated in high proportion of patients with JAK2 positive MPN. Despite the negative impact of ASXL1 in patients with non-MPN myeloid neoplasms, the patients with combined positivity of JAK2 and ASXL1 in this study had a very good OS probability. Age was a predictor of OS in the univariable and multivariable models. We recommend the development and the assessment of ASXL1 inhibitors as therapeutic strategies in patients with MPN. Disclosures Al-Khabori: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

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High Dose Imatinib Induction Therapy (800 mg/day, 6 Months) In Pre-Treated Chronic Phase CML Patients Improves Cytogenetic and Molecular Responses but Does Not Improve Overall and Progression Free Survival – Final Results of the CELSG Phase III CML11 “ISTAHIT” Trial

Blood ◽

10.1182/blood.v116.21.2271.2271 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2271-2271

Author(s):

Andreas L Petzer ◽

Dominic Fong ◽

Thomas Lion ◽

Irina Dyagil ◽

Zvenyslava Masliak ◽

...

Keyword(s):

Board Of Directors ◽

Induction Therapy ◽

Research Funding ◽

De Novo ◽

Chronic Phase ◽

Phase Iii ◽

High Dose ◽

Molecular Response ◽

Advisory Committees ◽

Grade 3

Abstract Abstract 2271 Introduction: Imatinib 400 mg/day represents the current standard treatment for de novo as well as pre-treated CML patients in chronic phase (CP). Recent randomized phase III trials revealed conflicting results concerning the potential higher efficacy of dose-increased imatinib in de novo treated CP-CML. Methods: We here present the final analyses including response data, OS, EFS and PFS of the multicenter, randomised, 2-arm phase III CELSG “ISTAHIT” trial evaluating imatinib high dose (HD) induction (800 mg/day, 6 months) followed by 400 mg/day as maintenance (experimental arm B) compared to continuous imatinib standard dose (400mg/day; arm A) in pre-treated CP CML patients. ClinicalTrials.gov Identifier: NCT0032726. Results: From a total of 243 patients screened for inclusion, 16 patients were not eligible (mainly due to non sufficient numbers of metaphases obtainable from the bone marrow before the start of the study). Of the remaining 227 patients, 113 patients were randomized into arm A and 114 patients into the experimental arm B. Subsequent data are presented as per protocol. No significant differences between treatment groups were observed regarding sex (55.5% female, 44.5% male), age (median: 46.3 years, range 18 –76), Sokal scores at diagnosis (30% low, 41% intermediate, 16% Sokal high risk, 13% unknown) and different pre-treatments, which included hydroxyurea (96%), interferon (72%), busulfan (17%) and “others” (26%; mainly Ara-C). The median observation time was 673 days. Cytogenetic responses were generally higher in the experimental arm B and revealed statistically significant differences in major cytogenetic responses (MCyR) at 3 and 6 months (month 3: 25.8% arm A, 48.3% arm B, p=0.002; month 6: 41.9% arm A, 58.8% arm B, p=0.029) as well as in complete cytogenetic responses (CCyR) not only during imatinib HD therapy (month 3: 7.5% arm A, 29.9% arm B, p<0.001; month 6: 20.4% arm A, 47.4% arm B, p<0.001) but also thereafter (month 12: 31.8% arm A, 52.9% arm B, p=0.006). The primary endpoint of the study, the achievement of an improved MCyR at 12 month was, however, not significantly different (56.8% arm A, 64.4% arm B). In line with improved cytogenetic responses, major molecular response (MMRIS) rates were also significantly better at 3, 6 and even at 24 months in the HD arm B (month 3: 3.7% arm A, 15.9% arm B, p=0.003; month 6: 9.4% arm A, 34.6% arm B, p<0.001; month 24: 26.5% arm A, 42.5% arm B, p=0.034). Surprisingly, however, this impressing improvement in cytogenetic and molecular remissions in patients achieving high dose imatinib as induction therapy did not translate into a better OS and PFS, both of which were comparable in the two treatment arms (OS: p=0.25; EFS: p=0.37). Moreover, the EFS was even significantly worsened in the experimental arm B (p=0.014). Grade 3/4 non-haematological toxicities during the first 6 months of therapy were comparable, whereas grade 3/4 haematological toxicities were significantly more common in the imatinib HD arm B. Conclusions: Although high dose imatinib induction induces more rapid and higher cytogenetic and molecular remission rates in pre-treated CP CML patients, OS as well as PFS were not improved and EFS was even worsened in the high dose induction arm B. Therefore we conclude that imatinib 400mg/day remains the standard of care for pre-treated CP-CML patients. Disclosures: Petzer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Imatinib 800mg is not licensed as the initial therapy of chronic phase CML. Lion: Novartis: Honoraria, Research Funding. Bogdanovic: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Griskevicius: Novartis: Research Funding. Kwakkelstein: Celgene: Employment. Rancati: Novartis: Consultancy, Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gastl: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wolf: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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90Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

Blood ◽

10.1182/blood.v116.21.594.594 ◽

2010 ◽

Vol 116 (21) ◽

pp. 594-594 ◽

Cited By ~ 8

Author(s):

Anton Hagenbeek ◽

John Radford ◽

Achiel Van Hoof ◽

Umberto Vitolo ◽

Ama Z.S. Rohatiner ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Induction Therapy ◽

Research Funding ◽

Myelogenous Leukemia ◽

Control Group ◽

Advanced Stage ◽

Ibritumomab Tiuxetan ◽

Advisory Committees

Abstract Abstract 594 The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39–0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42–0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27–0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30–1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were – for the greater part – rituximab-naïve. Disclosures: Hagenbeek: Roche Global Advisory Board: Consultancy. Radford:Schering (May 2009): Honoraria, Membership on an entity's Board of Directors or advisory committees. Vitolo:Roche Italy: Membership on an entity's Board of Directors or advisory committees; Celgene Italy: Membership on an entity's Board of Directors or advisory committees. Soubeyran:Roche: Honoraria, Research Funding; Cephalon: Research Funding. Bischof Delaloye:Expert Statement (questions of reimbursement in Switzerland): Honoraria. Morschhauser:Roche: Honoraria, Paid expert testimony within the past 2 years; Bayer: Honoraria.

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Outcomes of Abdominal Thrombosis in Patients with Myeloproliferative Neoplasms in a Single Center Experience

Blood ◽

10.1182/blood-2018-99-113318 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4307-4307

Author(s):

Douglas Tremblay ◽

Alexander Vogel ◽

Erin Moshier ◽

Ronald Hoffman ◽

Marina Kremyanskaya ◽

...

Keyword(s):

Overall Survival ◽

Hepatic Encephalopathy ◽

Board Of Directors ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Single Center ◽

Advisory Committees ◽

Vein Thrombosis ◽

Single Center Experience ◽

Significant Difference

Abstract Background Abdominal thrombosis (AT) is a concerning complication of myeloproliferative neoplasms (MPNs), leading to significant morbidity and mortality. While the epidemiology of AT in MPNs has previously been described, outcomes based on timing of AT relative to MPN diagnosis are unknown. Additionally, it is unclear how the treatment of the MPN affects outcomes including esophageal variceal bleeding (EVB), development of ascites, and additional thrombosis. Methods We conducted a retrospective review of patients at a single tertiary care institution. Inclusion criteria included: 18 years or older, a diagnosis of an MPN, including polycythemia vera (PV), myelofibrosis (MF), essential thrombocythemia (ET), and AT, including portal vein thrombosis (PVT), Budd Chiari Syndrome (BCS), or other splanchnic vein thrombosis. Primary outcome measures included EVB, additional thrombosis, development of ascites, hepatic encephalopathy, and death due to any cause. Years to outcome events were calculated by Kaplan Meier analysis. Results Baseline disease characteristics are summarized in Table 1. Sixty-four eligible patients were identified, 46 (72%) were female. The median age at time of AT was 45 years (range, 18-89). PV was the most common MPN, followed by ET then MF. Sixty patients (95%) harbored a mutation in JAK2. Characteristics of the AT are summarized in Table 2. Twenty-nine patients (45%) were diagnosed with AT after the MPN, with a median of 44 months (1-288) between diagnoses. Nineteen patients (30%) were diagnosed with AT before MPN, a median of 4 months (1-90). Sixteen patients (25%) were diagnosed concurrently (within 1 month). There was no difference in age at diagnosis of MPN among the three groups, however, patients diagnosed with AT before MPN were significantly younger (37 [18-89]) than those diagnosed with an AT after MPN (52 [31-85]) or concurrently (48 [20-70]) (p=0.0045). There was no significant difference among these three groups with respect to other AT characteristics. The median overall survival (OS) of the cohort was not reached. Five-year OS probability was 98%. No significant difference in overall survival (OS) was observed among those diagnosed with an AT before, concurrent, or after being diagnosed with an MPN. Treatment of the AT was primarily with warfarin (39%), although 19% of patients were treated with a direct oral anticoagulant. Additionally, 20% of patients received a transjugular intrahepatic portosystemic shunt (TIPS). Seven patients (11%) received no treatment for their AT. Of the entire cohort, 16 patients (25%) experienced an EVB. For patients who were on MPN directed therapy at time of AT, the hazard ratio (HR) for years to bleeding event was 1.24 (0.28-5.57) as compared to those who were not treated (p=0.7798). Ten patients (15.6%) experienced a non-abdominal thrombosis, predominantly deep vein thrombosis or pulmonary embolism. Thirty patients went on to develop ascites. HR for years to ascites from thrombosis was 1.94 (0.17-21.64) in the MPN treated patients (p=0.5823). Six patients (9%) developed hepatic encephalopathy. There was no difference between the MPN treated patients and non-MPN treated patients in a composite outcome of EV bleed, additional AT, ascites, or hepatic encephalopathy. Conclusions In this single center experience, a significant portion of patients were diagnosed with an AT before their MPN diagnosis. Treatment of the MPN at time of AT diagnosis did not appear to affect outcomes including EVB, additional thrombosis, development of ascites, or hepatic encephalopathy. These results suggest that once developed, treatment of the underlying MPN may not decrease complication rates of an AT. Further analyses are underway to clarify whether this finding is true in each AT subtype. Disclosures Hoffman: Merus: Research Funding; Summer Road: Research Funding; Formation Biologics: Research Funding; Janssen: Research Funding; Incyte: Research Funding. Kremyanskaya:Incyte: Research Funding. Mascarenhas:Merck: Research Funding; Promedior: Research Funding; Novartis: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding.

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