An Outpatient Management for First Cycle of Venetoclax and Hypomethylating Agents Results in Reduced Infection Rate and Hospitalizations in Acute Myeloid Leukemia Patients

Abstract Introduction In the setting of clinical trials Venetoclax (VEN) combined with hypomethylating agents (HMAs) has shown fair activity in Relapsed/Refractory (R/R) AML and impressive results in newly diagnosed (ND) elderly AML patients. However, no clear guidelines are available on real-life management, especially in the outpatient setting. This study involving AML patients treated with VEN combined with HMAs aims to amelioratate physicians' knowledge about the administration of these regimens. Methods This is a single-center retrospective study involving AML patients treated with Venetoclax combined with HMAs. Data were collected in accordance with GCP and Helsinky declaration. Adverse events (AEs) were graded according to CTCAE v4.03. Survival is estimated with Kaplan-Meyer method. Results A total of 59 AML patients, 43 R/R and 16 ND, have been treated with VEN plus HMAs from March 2018 to June 2021 and completed at least 1 therapy course (range 1-9, median 2, IQR 1.0 - 4.0). The median age was 70 (range 22-88) years and 15.3 % had a documented ECOG score greater than 1. VEN was combined with azacitidine in 35/59 (59.3 %) patients and with decitabine in 22/59 (37.3 %) patients (Table 1: patient and disease characteristics). The majority of patients (40/59, 67.8 %) (28/43 R/R, 12/16 ND) received the first cycle as out-patients, 19 out of 59 (32.2 %) patients were hospitalized and used as control. No significant differences with regards to disease and patients' characteristics were observed between in- and out-patients. During the ramp-up phase only 2 cases of tumor lysis syndrome (TLS) and 5 AEs were documented. During the first course, a total of 54 AEs were recorded and experienced by 16 over 19 hospitalized patients (84.2 %) and 20 over 40 outpatients (50 %). The 30-day and 60-day mortality were 2.5% (1/40) and 20 % (8/40), respectively, among patients receiving first course as out-patents, comparable to those documented in hospitalized patients. Overall, we reported 118 AEs, of which 74 were grade III-IV and the most common were hematological 23/74 (31.1 %) or infective 41/74 (55.4 %). Regarding infections, at least one bacterial infection was experienced in 10/40 (25%) and 12/19 (63.1%) patients of the outpatient and hospitalized cohorts, respectively (p = 0.009, IC 1.37 - 19.74, OR 4.98). Pneumonia and sepsis (13 and 18 cases) were the most frequent infections. Sepsis incidence was higher among hospitalized patients (13/19, 68.4 %, vs 5/40, 12.5 %, p = 0.000029). No significant difference in infective risk was documented between R/R and ND patients (65.1 vs 50 %). Thirty-two out of 59 (54.2 %) patients experienced at least one VEN withdrawal due to treatment toxicity. Twenty out of 43 AEs requiring VEN suspensions occurred during the first cycle. Patients treated in-patient showed the tendency for a higher probability to suspend therapy due to treatment toxicity (10/19 IN vs 10/40 OUT, p = 0.04). While twenty-three out of 59 (38.9 %) patients were hospitalized for treatment complications at least once, the average number of days spent in hospital was significantly different between patients receiving the first course as outpatients as compared to those who were hospitalized (5.9 vs 39.7, respectively, p < 0.0001). With a median follow-up of 117 days (IQR 92 - 173.75) in ND patients the Overall Response Rate (ORR), defined as CR + CRi + HI, was 62.5 % (10/16), with a CR/CRi rate of 50 % (8/16) and a median OS of 247 days (95% C.I. 177.71- 316.58)(Fig 1a). In the R/R setting the ORR rate was 41.8 % (18/43), with a CR/CRi rate of 25.6 % (11/43) and a median OS of 219 days (95% C.I. 91.8 - 346.2) (Fig 2a). No differences in OS were documented between patients who underwent VEN plus HMAs outpatient and patients who underwent the first cycle hospitalized (p = 0,38) (Fig. 1b-2b). Conclusions With the limitations of a single-center retrospective study, our real-life data indicate that VEN plus HMAs is feasible in an outpatient management, with minimal TLS rate and no limiting toxicities. Of note, infections rate was acceptable, bacterial infections and sepsis risk were lower in outpatients than in hospitalized patients. There was no significant impact of the outpatient management on treatment effectiveness, with data in line with published AML cohorts. Further studies evaluating the clinical, social and economic impact of outpatient VEN-based treatments are highly warranted. Figure 1 Figure 1. Disclosures Papayannidis: Pfizer, Amgen, Novartis: Honoraria. Cavo: Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Venetoclax Plus Hypomethylating Agents for Relapsed/Refractory Acute Myeloid Leukemia (AML) Is Safe and Manageable in the Outpatient Setting

Blood ◽

10.1182/blood-2020-138719 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-15

Author(s):

Jacopo Nanni ◽

Cristina Papayannidis ◽

Gianluca Cristiano ◽

Giovanni Marconi ◽

Chiara Sartor ◽

...

Keyword(s):

Tumor Lysis Syndrome ◽

Real Life ◽

Outpatient Setting ◽

Hospitalized Patients ◽

Hypomethylating Agents ◽

Single Center ◽

Outpatient Management ◽

Tumor Lysis ◽

Elderly Aml ◽

Treatment Naïve

JN and CP equally contributed Introduction In the setting of clinical trials Venetoclax (VEN) combined with hypomethylating agents (HMAs) has shown fair activity in R/R AML and impressive results in treatment-naïve elderly AML patients. However, no clear guidelines are available on real-life management, especially in the outpatient setting. This study involving R/R AML patients treated with VEN combined with HMAs aims to amelioratate physicians' knowledge about the administration of these regimens. Methods This is a single-center retrospective study involving AML patients treated with Venetoclax combined with HMAs. Data were collected in accordance with GCP and Helsinky declaration. Adverse events (AEs) were graded according to CTCAE v4.03. Survival is estimated with Kaplan-Meyer method. Results Thirty-one R/R AML patients have been treated with VEN plus HMAs from March 2018 to March 2020 and completed at least 1 therapy course (range 1-9, median 2, IQR 1.0 - 5.0) (Table 1: patients' characteristics). Seventeen out of 31 (54,8 %) had received intensive chemotherapy as induction therapy. Twenty-two patients (71 %) had already received HMAs therapy, of which 14/31 (45,2 %) as first and only previous line of therapy. VEN was combined with azacitidine in 13/31 (41,9%) and with decitabine in 18/31 patients (58.1 %). The majority of patients (22/31, 70,9%) received the first cycle as out-patients, special focus of our analysis. For clinical reasons, only 9 out of 31 (29,1 %) patients were hospitalized and were used as control. In the outpatients setting, VEN dose escalation was managed with at least a weekly laboratory and clinical monitoring and the drug was often increased more slowly to carefully prevent tumor lysis syndrome or other complications. Specifically, there has been a trend toward a ramp-up schedule different from that indicated in clinical trials in the outpatient setting in comparison with hospitalized patients (77,2 % vs 33,3 %). In term of safety, no cases of tumor lysis syndrome (TLS) and only 2 AEs were documented during ramp-up phase, both experienced by hospitalized patients. Seventeen AEs were documented during cycle 1, affecting more frequently hospitalized patients (77,9% vs 31,8 %). In the outpatient setting, the early 30-days and 60-days mortalities were 4,5 % (1/22) and 13,6 % (3/22), respectively, comparable to percentages documented in hospitalized subgroup (0% and 11,1%). Overall, with a median follow-up of 138 days (IQR 69 - 285), we reported 48 AEs, of which 28 were grade III-IV and the most common were hematological (13/28, 48,1 %) or infective (14/28, 51,8 %). Twenty out of 31 (64,5 %) patients reduced VEN dosage during treatment, of which 12/20 (60 %) due to occurring AEs, and remaining patients for azole coadministration. Eleven out of 31 (35,5 %) patients required hospitalization, specifically 3 out of 9 hospitalized patients (33,3 %) during the subsequent outpatient phase of treatment, and 8/22 (36,3 %) patients who underwent VEN therapy outpatient, of which only 2 during the first 28 days of treatment. Twenty-four and 5 AEs were followed by a VEN temporary (median duration 14 days, range 5-120) and permanent withdrawn, respectively. As for the rate of response, the Overall Response Rate (ORR) by VEN plus HMAs therapy in our R/R study population, defined as CR + CRi + HI, was 41,9 % (13/31), with a CR/CRi rate of 22,6 % (7/31). The median time to first response was 67.0 days (IQR 37.0 - 133.5) and the median duration of response was 131.0 days (IQR 89.0 - 151.0). Four out of 31 (12,9 %) patients received subsequent HSCT. The median OS was 285 days (95% C.I. 178 - 392), with no difference in OS between patients who underwent VEN plus HMAs outpatient and patients who underwent the first cycle hospitalized (p = 0,38). Conclusions With the limitations of a single-center retrospective study, our real-life data indicate that VEN plus HMAs is feasible in an outpatient management, without TLS or other limiting toxicities and with comparable early-mortality and toxicity profiles, even in the ramp-up phase and first therapeutic cycle. There was no significant impact of the outpatient management on treatment effectiveness, with data in line with published R/R AML cohorts. Further studies evaluating the clinical, social and economic impact of outpatient VEN-based treatments are highly warranted. Disclosures Papayannidis: Abbvie, Janssen, Novartis, Amgen, Pfizer:Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive:Consultancy, Honoraria. OffLabel Disclosure: In R/R AML, available data regarding the combination of VEN plus HMAs come only from retrospective studies where VEN is administered as an off-label prescription due to its widespread approval for chronic lymphocytic leukemia due to promising results obtained in treatment-naive elderly AML patients

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Impact of Anti-CD20 Antibodies on the Incidence of Secondary Cancers in Patients Treated for Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v126.23.5291.5291 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5291-5291

Author(s):

Stéphanie Guidez ◽

Hélène Demarquette ◽

Morgane Nudel ◽

Charline Le Grand ◽

Eileen Boyle ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

Chronic Lymphocytic Leukemia ◽

Board Of Directors ◽

Single Agent ◽

Lymphocytic Leukemia ◽

Advisory Committees ◽

Secondary Cancers ◽

Advisory Boards ◽

Significant Difference

Abstract Background: An increased incidence of second primary malignancies (SPM) is described in chronic lymphocytic leukemia (CLL). Current hypothesis to explain this phenomenon mainly relies on immunosuppression conferred by both CLL itself and CLL treatment. The imputability of fludarabine has been long recognized but the risk associated with monoclonal antibodies, especially rituximab recently shown to improve overall survival in CLL when combined with fludarabine and cyclophosphamide (FC), remains unknown. Materials and methods: We conducted a retrospective study of the incidence of secondary cancers in 1255 CLL patients diagnosed since 1980 in the University Hospital of Lille to better characterize the possible risk of SPM associated with rituximab Results: Of 1255 patients, 651 (52%) received therapy including rituximab (38%), FC (26.7%), F alone (22.4%), chlorambucil (27.5%), alemtuzumab (15.5%) and bendamustine (9.3%). Rituximab was given either in combination with FC (27.5%), other chemotherapy (2.6%) or as a single-agent (3.5%). There was no significant difference in terms of age (58 versus 62 years), gender, Binet stage, cytogenetic abnormalities and number of regimen received between patients treated with or without rituximab. Median follow-up was 6 years for all patients (range 2-23), 4.8 years (range, 2-8) since initiation of therapy for patients treated without rituximab and 3.6 years (range, 0.2-11) for patients who received rituximab. Median overall survival (OS) was 18 years for patients treated with R-chemotherapy versus 11 years for patients treated with chemotherapy alone (p<0,001). Of 1255 patients, 21.5% were diagnosed with SPM. The incidence of SPM was 17.1% in patients who did not receive treatment compared to 10% in those treated. Among treated patients, the incidence of SPM was significantly higher (19% v 2%) in patients who received rituximab (p <0.001). SPM incidence was increased after R-FC (24.4%), FC (10.5%) compared to other regimen (p<0,001) (table1). Most frequent SPM were skin (25%)-and urologic cancers (23%). Median onset of SPM was 5 years (range, 2-20) without rituximab and 2 years (range, 1-7) with rituximab. Table 1. Incidence of SPM p Treatment, %- Purine analogs- FC- RFC- Chlorambucil- Bendamustine- Alemtuzumab- CorticothŽrapie - 1,9 10,5* 24,4* 4,9 0 3,5 0 <0,001 Conclusion: In this large single center retrospective study, we found an earlier and significantly increased incidence of SPM, mainly skin cancers, in CLL patients treated with R-chemotherapy compared to those given chemotherapy alone. It remains to be determined whether this increased SPM incidence is a due to a direct toxicity of rituximab or merely a collateral consequence of improved OS observed after rituximab. Disclosures Facon: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Cazin:ROCHE: Consultancy; MUNDIPHARMA: Honoraria, Research Funding; NOVARTIS: Honoraria; GILEAD,: Honoraria. Morschhauser:Genentech Inc./Roche: Other: Advisory boards.

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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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Anti-MAG Neuropathy: a Single Center Retrospective Study In 61 Patients

Blood ◽

10.1182/blood.v116.21.3951.3951 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3951-3951

Author(s):

Marie-Anne HOSPITAL ◽

Sonia Dragomir ◽

Vincent Levy ◽

Jean Neil ◽

Lucile Musset ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Response Rate ◽

Immunoglobulin M ◽

Response To Treatment ◽

First Line ◽

Advisory Committees ◽

Significant Difference ◽

Before And After

Abstract Abstract 3951 Background: Polyneuropathy is the most frequent neurological complication in Waldenstrom macroglobulinemia (WM). Most patients have an insidiously progressive distal symmetric sensorimotor and ataxic neuropathy due to a monoclonal immunoglobulin M anti-myelin-associated glycoprotein (MAG). There is still no treatment reference today. Recent studies underline the interest of Rituximab (RTX) but its efficacy is not yet proven. In order to identify the interest of immunotherapy, we performed a retrospective study in 61 patients with anti-MAG over a period of 12 years. Methods: All patients underwent neurological, biological (anti-MAG antibodies, IgM serum) and electrophysiological examination before and after each treatment. Clinically, patients were considered to be improved if they had a decrease of at least two points on the INCAT sensory sum score and/or a decrease of 20 mm on the visual analogue scale and/or motor strength improvement by at least two MRC points in the ankle dorsiflexor. Biologically, response anti-MAG antibodies and IgM serum were considered to be improved if their level was diminished by half. Electrophysiological studies were performed using standard procedures. Results: A total of 61 patients were analyzed. The median age at onset was 64 years (range 33–84), median serum IgM concentration 4.6 g/L (0-17), median anti-MAG antibodies 49900 BTU (23000>70000), RANKIN score 1 (35 patients), 2(20 patients), 3(6 patients). Twenty-five patients had WM with lymphoplasmacytic cells bone marrow infiltration. None of the patients had criteria for therapy initiation according to the 2th international workshop except symptomatic or evolving neuropathy. In first line, 45 patients were treated with Chlorambucil (CBL) (8 improved, 28 were stabilised, 9 worsened), 16 patients were treated with RTX alone (9) or in combination (7) (11 improved, 2 were stabilised, 3 worsened). RTX gave a significant higher response rate compared with CBL (p=2×10-4). With a median follow up of 96 months, 15 patients treated with CBL relapsed. Only one patient treated with RTX relapsed but the median follow up was not reached (60 months follow up). In the CBL group, 15 patients were treated at relapse with RTX and 11 improved, 3 were stabilised, 1 worsened. The average time follow up of the 2nd response was 48 months. Twelve patients in failure were treated with RTX: 8 improved, 1 was stabilised, 3 failed with an average follow up of 48 months. There was no significant difference between anti-MAG antibodies level before and after treatment (p=0.64) in patients in response but a low IgM level was associated with response to treatment (p<0.029). Conclusion: In first line, RTX alone or in combination is associated with a higher response rate than CBL. For patients who relapsed after CHL, patients favourably responded to RTX with an average time follow up of 48 months. IgM level is a prognosis factor (p<0.029) for clinical response to treatment. To better define the efficacy of RTX in this setting, results of a french randomized study comparing RTX to placebo are pending. Disclosures: Choquet: Roche: Consultancy. Leblond:ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees.

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Lenalidomide in Pretreated Mantle Cell Lymphoma Patients: An Italian Observational Multicenter Retrospective Study in Daily Clinical Practice, the Lenamant Study

Blood ◽

10.1182/blood.v126.23.3946.3946 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3946-3946 ◽

Cited By ~ 3

Author(s):

Vittorio Stefoni ◽

Cinzia Pellegrini ◽

Letizia Gandolfi ◽

Luca Baldini ◽

Monica Tani ◽

...

Keyword(s):

Retrospective Study ◽

Mantle Cell Lymphoma ◽

Board Of Directors ◽

Cell Lymphoma ◽

Real Life ◽

Disease Free Survival ◽

Phase Iii ◽

Good Survival ◽

Advisory Committees ◽

Mantle Cell

Abstract Mantle cell lymphoma (MCL) is an uncommon type of non- Hodgkin lymphoma (NHL) comprising <10% of all newly diagnosed patients. Classified as an aggressive NHL subtype, MCL has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Conventional first-line therapy for bulky or advanced disease primarily consists of chemotherapy combined with rituximab, with possible consolidation with autologous stem cell transplantation for younger patients in remission to improve overall patient outcomes. However, options for relapsed MCL are limited although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL (without any other therapeutic options) since May 2011, based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on efficacy and safety of lenalidomide use in real practice. Seventy patients received lenalidomide for 21/28 days with a median of 8 cycles. Doses (range 5-25 mg/day) were according to hematologic parameters. At the end of therapy there were 22 complete responses (31.4%), 9 partial responses, 6 stable diseases and 33 progressions with an overall response rate of 44.3%. Sixteen patients (22.9%) received lenalidomide in combination either with dexamethasone (N=12) or with rituximab (N=4). At 62 months overall survival (OS) was 26.2% (median reached at 33 months) and disease free survival (DFS) 37% at 42 months: 14/22 patients are in continuous complete response with a median of 26 months. We compared patients who received lenalidomide alone with patients who received lenalidomide in combination with other drugs: OS and DFS did not differ. Progression free survivals are significantly different: at 56 months 36% in combination group vs 13% in patients who received lenalidomide alone (p=0.04, hazard ratio 0.52). Toxicities were manageable, even if 17 of them led to an early drug discontinuation. Two secondary malignancies occurred: a myelodysplastic syndrome and a lung cancer after 10 and 15 months of therapy, respectively. There is a boundary zone in the passage from phase III to phase IV trials, i.e. from experimental to marketing and free use phases: in this zone we can find named patient program, compassionate and off-label use and, in Italy, request based on a local disposition. Despite the known potential bias of all the observational studies, reports on the real life experience make an important contribution to medical knowledge prior to market authorization: lenalidomide therapy is effective and tolerable also in compassionate use patients with good survival. Our results, in fact, are superimposable to those obtained in clinical trials. Disclosures Rusconi: Roche: Honoraria. Zinzani:Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees.

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Real-World Patterns of Utilization and Outcome of Market Approved Lenalidomide-Based Triplet Combinations in First Relapsed Multiple Myeloma Patients: Evidence from a Propensity Score Matched Analysis

Blood ◽

10.1182/blood-2021-146908 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4109-4109

Author(s):

Silvia Mangiacavalli ◽

Monica Galli ◽

Sara Pezzatti ◽

Angelo Belotti ◽

Francesca Fazio ◽

...

Keyword(s):

Multiple Myeloma ◽

Propensity Score ◽

Board Of Directors ◽

Randomized Clinical Trials ◽

Real Life ◽

Advisory Board ◽

Cell Transplant ◽

Advisory Committees ◽

Significant Difference ◽

First Relapse

Abstract Background: Lenalidomide (R) plus dexamethasone (d) triplet combinations have been indicated by ESMO guidelines as standard of care in first relapse for lenalidomide sensitive multiple myeloma (MM) patients (pts) (Dimopoulos et al, 2021). Meta-analysis of randomized clinical trials (RCT) shows better outcome with the combination of Daratumumab + Rd (DaraRd) over other Rd-based combinations (carfilzomib+Rd (KRd), elotuzumab+Rd (EloRd), Ixazomib+Rd (IxaRd). There are few real-life studies focusing on the pattern of utilization and outcome of different Rd triplets in first relapse MM. Aims: To explore performances of market-approved Rd-based triplets in unselected MM pts in first relapse. Patients and methods: After ethics committee approval, we review data of 366 MM pts in first relapse consecutively addressed to Rd-based triplets according to market-approved schedule after 2017. Rd-based therapies was distributed as follows: DaraRd 51.6% (189 pts), KRd 36.1% (132 pts), EloRd 8.7% (32 pts), IxaRd 3.6% (13 pts). Given the limited number of pts treated with IRd and EloRd, the analysis is focused only on DaraRd and KRd group after further excluding 51 pts (13%) addressed to salvage autologous stem cell transplant (ASCT) after daraRd (n=9)/KRd(n=42) fixed induction. Few pts in both groups were previously exposed to R/K/Dara (respectively 12 pts (3%), 8 (2%), 0). Treatment choice was influenced by market approval, with KRD regimen used more commonly in the IQR 2017- 2019, while DaraRd more commonly in the IQR 2018-2020. To limit the bias of a retrospective observation, we calculated a propensity score and we used it (after trimming of 5% of observations) to re-weight the data, according to the Inverse Probability of Treatment method (IPTW analysis). For the estimation of the propensity score, we used: age at Rd-triplet starting, ISS stage, presence of high-risk FISH, previous exposure to Bortezomib, previous ASCT, good response at first-line therapy (≥VGPR), time between diagnosis and relapse, myeloma defining events at diagnosis, type of relapse (symptomatic/biochemical), center. Details of these characteristics are reported in table1. Of note, pts addressed to DaraRd were slightly older (68,7 vs 63,4 years in KRd, p<0.001), time from diagnosis was quite longer (3,5 vs 2,9 year in KRd, p=0.094), they received a lower rate of prior ASCT (56% vs 72% in KRd, p=0.008). After a median follow-up of 21.6 months (IQR: 9.6-32.4), response rate ≥PR were similar in both groups (92% in DaraRd vs 87,6% in KRd, IPTW analysis: OR=0.8, 95%CI: 0.4-1.5, p=0.422). No significant difference was found in terms of ≥VGPR (60% in DaraRd vs 62,9% in KRd, IPTW analysis: OR=0.7, 95%CI: 0,4-1,1 p=0.098) as well as of ≥CR (16,6% in DaraRd and 23,6% in KRd, IPTW analysis: OR=1,3, 95%CI: 0.8-2,2, p=0.340). The median number of administered cycles was higher for DaraRd (12 vs 10, IPTW analysis: β: 0.2, 95%CI: 0.1-0.4, p=0.025). Discontinuation rate was lower with DaraRd (28% vs 62% with KRd, IPTW analysis: OR: 0.3, 95%CI: 0.2-0.4, p<0.001). Most patients in both groups discontinued treatment for progression (55,3% with DaraRd and 59.3% with KRd), discontinuation for TEAE was reported respectively in 38,3% in DaraRd and 31,5% in KR; 6,4% of pts in DaraRd and 9,2% in KRd discontinued treatment for pts decision. Weighted analysis shows a similar outcome. In particular, the median PFS is 28 months for DaraRd vs 23 months for KRd, (HR=0.9, 95%CI: 0.6-1.2, p=0,420) (Figure 1). At left-truncation analysis, patients with ≥VGPR, had similar PFS when comparing DaraRd vs KRd (HR=1.0, 95%CI: 0.6-1.6, p=0.896) while in patients with ≤PR, DaraRd showed a longer PFS (HR=0.5, 95%CI: 0.3-0.9, p=0.012) (Figure 2). The median TTNT was 31 and 29 months in DaraRd and KRd, respectively (HR=0.8, 95%CI: 0.5-1,1 p=0,111). No difference was found in terms of OS (HR=1.2, 95%CI: 0.8-1.8, p=0.408)(Figure 3). Conclusions: Our real-life study shows that DaraRd represents the most commonly received regimen at first relapse followed by KRd triplet. After propensity score matching, DaraRd and KRd combinations proved to be both effective with similar outcomes when used early in the treatment history, after one line of therapy. This study, in addition, points out the possible gap of outcome between RCT and clinical practice. Figure 1 Figure 1. Disclosures Mangiacavalli: BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; GSK: Honoraria. Galli: BMS, Celgene, Janssen, Sanofi, Takeda: Honoraria. Belotti: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees. Fazio: Janseen: Honoraria. Petrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board.

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Polatuzumab Vedotin Use before Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Aggressive Lymphoma: A US Single Center Experience

Blood ◽

10.1182/blood-2021-152313 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3842-3842

Author(s):

Arushi Khurana ◽

Radhika Bansal ◽

Matthew Hathcock ◽

Adrienne Nedved ◽

Yucai Wang ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Advisory Board ◽

Single Center ◽

Infection Rates ◽

Bridging Therapy ◽

Advisory Committees ◽

Single Center Experience ◽

Significant Difference ◽

Car T

Abstract Background: Polatuzumab vedotin (Pola), an antibody drug conjugate targeting CD79b received FDA approval in combination with bendamustine and rituximab (Pola-BR) in June 2019. With CAR-T as destination therapy, the option of Pola-BR appears appealing with its superior efficacy and lack of potential interference with CAR-T due to different target antigens. However, clinical concerns remain regarding prolonged lymphopenia associated with benda and CAR-T manufacturing if used before apheresis. We reviewed the single center experience of all patients with exposure to polatuzumab around CAR-T for R/R aggressive NHL treated at Mayo Clinic Rochester. Methods: A review of patients that received at least one dose of Pola with the intent to proceed to CAR-T between July 1, 2019 and March 31st, 2021 at Mayo Clinic, Rochester were included. Response to therapy was based on 2014 Lugano criteria. Overall survival (OS) was defined as the time from CAR-T infusion to death, and event-free survival (EFS) as the time from CAR-T infusion to disease progression, next treatment, or death. Survival curves were calculated using Kaplan-Meier estimates, and were compared between subgroups using the log-rank test. Cox regression was used for multivariate analysis (MVA). Results: A total of 22 patients were identified during the study period. Of these 18 (82%), made it to CAR-T infusion (17 axi-cel, and 1 -tisa cel). 3 patients died due to progressive disease (PD) before CAR-T and one achieved complete remission (CR). In the pre-CAR-T Pola cohort (n = 22), the median age was 65.5 years (39-73), 50% were males, 96% had advanced stage and IPI ≥ 3. Median prior lines of treatment were 4.5 (2-6), 73% had primary refractory disease and 50% had myc rearrangement. 19 (86%) patients received Pola as bridging therapy and 8 were exposed to Pola before T-cell apheresis. Bendamustine was included in the treatment for 79% (15/19) for bridging therapy and 63% (5/8) with exposure pre-apheresis. For those in the bridging group, the overall response rate (ORR) was 26% (5/19), with one patient achieving CR with Pola-BR. Disease control (defined as those in a partial response [PR] or stable disease [SD]) was seen in 47% (9/19) patients. One of the 8 patients with pre-apheresis exposure to Pola, required an additional attempt at CAR-T manufacturing after the initial failure. At a median follow up of 48 weeks, the EFS and OS in 18 patient cohort with pre-CAR-T Pola exposure were 6.7 weeks (95% CI, 4.3-not reached [NR]) and 15 weeks (95% CI, 9.7-NR), respectively. At the data cut off (7/25/2021), 78% patients had died. As traditional chemo for bridging is a particularly poor prognostic group, we compared Pola-BR bridging group (n = 15), to other traditional chemo bridge group (n = 16) in our CAR-T database. Both groups had comparable baseline characteristics as shown in Table 1 except for higher proportion of patients with B-symptoms in the Pola-BR group at time of CAR-T. There was also no difference in the inflammatory markers (CRP and ferritin) at LD or peak level after CAR-T. Table 2 shows outcomes between the 2 groups with comparable any grade CRS, neurotoxicity, pre and post CAR-T infection rates. Best response ORR to CAR-T was higher in the other chemo group vs. Pola BR (81.2% vs. 33%, p = 0.027). There was a significant difference in the 6-month OS rate (other 81.3% [95%CI, 54.5-96] vs. pola 33.3% [95%CI, 11.8- 61.6], p = 0.007) but no significant difference in the 6-month EFS rate (other 37.5% [95%CI, 15.2-64.6%] vs. pola 13.3% [95%CI, 1.7-40.5%] p = 0.12) between the 2 groups (figure 1). On univariate analysis within the chemo type bridging cohort (Pola-BR + other traditional chemo, n = 31), presence of B-symptoms (HR 4.72, p = 0.002), ECOG PS > 2 at CAR-T (HR 6.75, p = 0.0008), and type of bridge therapy (pola HR 6.57, p = 0.009) were associated with worse OS whereas a response to bridge (PR+SD, HR 0.39, 0.031) was favorable. On MVA, association was maintained for bridge type (pola, p <0.001) and response to bridge (p <0.001). Discussion: Pola based bridge was feasible in this US based cohort without significant issues with CAR-T manufacturing or increased infection rates. However, in this retrospective analysis, use of Pola-BR was associated with inferior outcomes compared to other traditional chemotherapy options. Future studies are required to elucidate whether these difference in outcomes stem from a biological basis versus bias in patient selection. Figure 1 Figure 1. Disclosures Wang: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Genentech: Research Funding; InnoCare: Research Funding. Paludo: Karyopharm: Research Funding. Bennani: Kymera: Other: Advisory Board; Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Merck: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Juno: Consultancy; Vineti: Consultancy; Takeda: Research Funding; Gamida Cell: Consultancy; Legend: Consultancy; Sorrento: Consultancy.

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Retrospective Study on Hospital Admissions due to Pyelonephritis in Type II Diabetic Patients

Journal of Medical - Clinical Research & Reviews ◽

10.33425/2639-944x.1220 ◽

2021 ◽

Vol 5 (6) ◽

Author(s):

Dilraj Dhillon ◽

Thomas Randall ◽

David Zezoff ◽

Mouchumi Bhattacharyya

Keyword(s):

Retrospective Study ◽

Length Of Stay ◽

Hospital Admissions ◽

Type Ii Diabetes Mellitus ◽

Hospitalized Patients ◽

Diabetic Patients ◽

Clean Intermittent Catheterization ◽

Type Ii ◽

Indwelling Catheters ◽

Significant Difference

Background: Pyelonephritis is a urinary tract infection that ascends to involve the kidneys. It can also occur as an infection secondary to bacteremia. Some pathogens that commonly cause pyelonephritis are E. coli, enterobacteriaceae, staphylococci, and pseudomonas. The initial patient presentation usually involves fever, chills, nausea, vomiting, costovertebral angle tenderness, and flank pain. Other cystitis symptoms such as dysuria, increased urinary frequency, malodorous urine, and hematuria may or may not be present. Symptoms of pyelonephritis with bacteriuria are sufficient for the diagnosis of pyelonephritis. Aim: The aim of this study was to investigate a potential link between Type II Diabetes Mellitus and pyelonephritis. Methods: In this retrospective study, hospitalized patients during the study period were reviewed. Variables examined were sex, age, and length of stay. Patients were excluded if they had known urogenital abnormalities, indwelling catheters (Foley, nephrostomy, suprapubic, or who regularly perform clean intermittent catheterization), were pregnant, or were on dialysis. Results: Of 333 patients analyzed, diabetics had a longer length of stay then non-diabetics (4.49 vs 3.67 days respectively; p=0.0041) and females were significantly younger than men in hospitalized patients for pyelonephritis were (50.0 vs 63.5 years; p=<0.0001). Further, it was found that diabetics were significantly older than nondiabetics were (60.4 vs 47.3; p=<0.0001) and more diabetics getting admitted with pyelonephritis were men vs women (59.32% vs 35.27%; p=0.0007). Conclusion: Results of the study were significant in showing that of all pyelonephritis-hospitalized patients on average the length of stay was longer for diabetics and it demonstrated that female patients with pyelonephritis are significantly younger than male patients hospitalized with pyelonephritis. Of note, there was no significant difference in the length of stay for diabetic patients based on their treatment modality (diet controlled vs. oral medications vs. insulin dependent vs. combined). The study also showed that diabetics getting admitted for pyelonephritis are more men and older in age compared to the nondiabetics.

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Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses

Blood ◽

10.1182/blood-2019-124981 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1884-1884 ◽

Cited By ~ 1

Author(s):

Alfred Chung ◽

Gregory P. Kaufman ◽

Surbhi Sidana ◽

David Iberri ◽

Erik Eckhert ◽

...

Keyword(s):

Disease Progression ◽

Board Of Directors ◽

Median Duration ◽

Research Funding ◽

Control Group ◽

Al Amyloidosis ◽

Cell Transplant ◽

Advisory Committees ◽

Free Interval ◽

Significant Difference

Daratumumab (DARA) is a CD38-targeted antibody FDA-approved for the treatment of multiple myeloma (MM) and its efficacy has recently been demonstrated in the treatment of AL amyloidosis. DARA is conventionally given indefinitely until evidence of disease progression or intolerance for the treatment of MM. In AL amyloidosis, the optimal duration of therapy is not known, and patients may be treated indefinitely on maintenance, extrapolating from MM data. However, the plasma cell burden observed in AL amyloidosis is often lower than in MM, and thus certain patients achieving deep responses may have durable responses with time-limited treatment. Outcomes for patients who are observed after DARA discontinuation are not known. We report the outcomes of patients at our institution who received time-limited DARA. A retrospective analysis of AL amyloidosis patients treated at Stanford University from 2016 to 2019 with DARA monotherapy and dexamethasone for at least 2 months was performed, and patients who subsequently had DARA discontinued for reasons other than disease progression or lack of response were selected for the study. Hematologic responses were assessed by consensus guidelines. Duration on and off therapy were explored, along with time-to-next treatment or death (TTNT), defined as the time from DARA initiation to restarting/switching therapy or death. An exploratory analysis comparing TTNT between the study population and a control cohort who achieved hematologic CR and were maintained on DARA was conducted with the Kaplan-Meier method and log-rank testing. 67 patients received at least 2 months of DARA monotherapy and dexamethasone; among these, 15 patients discontinued therapy for reasons other than disease progression and were included. Median age was 66 years old and median lines of prior therapies was 4 (range: 1 - 6). Baseline difference between involved and uninvolved free light chains (dFLC) prior to DARA initiation was 2.6 mg/dL (range: 0 - 16.8 mg/dL). 10 of 15 patients had cardiac involvement with median NT-proBNP of 1982 pg/mL and 9 of 15 patients had renal involvement with median 24-hour proteinuria of 6.2 g and eGFR of 32 mL/min/1.73m2 at DARA initiation. Median duration from starting to stopping DARA was 7.8 months (range: 2 - 21 months). Median duration from achieving best hematologic response to stopping DARA was 3 months (range: 0 - 17 months). Reasons for discontinuation included: patient preference (5), fatigue/body aches (4), infection (2), other active medical comorbidities (3), and lack of perceived further benefit (1). At DARA discontinuation, median dFLC was 0.1 mg/dL (range: 0 - 2.2 mg/dL) and there were 12 hematologic CR, 1 VGPR, 1 PR, and 1 not assessable for response. Outcomes for all 15 patients are shown in Figure 1. The median treatment-free interval was 17.5 months (range: 5 - 34 months); estimated 2-year TTNT-free survival was 83% (95% CI: 61 - 100%). All 14 evaluable patients eventually achieved CR. 3 patients restarted DARA for rising dFLC, and all 3 patients demonstrated response to retreatment (2 achieving CR and 1 near PR with ongoing follow-up). There were 2 deaths. One patient with severe baseline cardiac amyloidosis developed sudden rise in dFLC after treatment-free interval of 21 months; although he rapidly achieved hematologic CR on retreatment, he died of heart failure within 2 months of restarting DARA. The other patient developed therapy-related AML while off therapy and underwent allogenic stem cell transplant but died of leukemia (censored for AL amyloidosis outcomes at transplant). There was no significant difference in the TTNT between the study group and a control group of 16 patients who achieved CR and were on continuous maintenance (Figure 2; p=0.807). AL amyloidosis patients achieving deep responses with DARA can have favorable outcomes after treatment discontinuation, including a long treatment-free interval. Although our sample size is small, the outcomes of these patients appeared comparable to those achieving CR on continuous DARA maintenance, and patients were able to regain responses when retreatment was necessary. These results suggest that DARA may be safely discontinued in patents achieving deep hematologic responses, which has significant implications for quality of life and financial burden of treatment. Future studies evaluating time-limited versus continuous DARA maintenance after achievement of deep responses are warranted. Disclosures Kaufman: Janssen: Other: travel/lodging, Research Funding. Liedtke:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celator: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Daratumumab for treatment of AL amyloidosis

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Outcomes of Patients with Relapsed or Refractory Acute Myeloid Leukemia Receiving Hypomethylating Agent and Venetoclax

Blood ◽

10.1182/blood-2019-128958 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1357-1357 ◽

Cited By ~ 2

Author(s):

Hannah Asghari ◽

Dasom Lee ◽

Yehuda E. Deutsch ◽

Onyee Chan ◽

Najla Al Ali ◽

...

Keyword(s):

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Risk Groups ◽

Initial Therapy ◽

Intermediate Risk ◽

Advisory Committees ◽

Significant Difference ◽

Frontline Therapy ◽

Refractory Aml

Background: Patients with acute myeloid leukemia (AML) have dismal overall outcomes and survival is exceptionally poor in patients who experience relapse or are refractory (R/R) to frontline therapy. Since December 2018, combination therapy with hypomethylating agents (HMA) and venetoclax (HMA+Ven) has become standard frontline therapy for older patients or younger unfit patients. Moreover, it has been routinely utilized in patients experiencing relapsed or refractory AML yet response and outcome data is limited in patients with R/R disease. Thus, we investigated outcomes after HMA+Ven in patients with relapsed or refractory AML. Methods: We retrospectively annotated 72 patients who received treatment with HMA+Ven at Moffitt Cancer Center and Memorial Healthcare System between 2017 and 2019. Patients were divided into two subgroups: 1) initial remission therapy and 2) salvage therapy. Clinical and molecular data were abstracted in accordance with the Institutional Review Board approved protocol. Overall response rate (ORR) included patients achieving complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia free state (MLFS). Patients achieving CR, CRi, or MLFS were termed as responders (RES) and patients without CR, CRi, or MLFS were nonresponders (NRES). Fisher's Exact method was used to determine significance for categorical variables. Kaplan-Meier analysis was performed to determine median overall survival (mOS) and log-rank test was utilized to determine significance. All p-values are two-sided. Results: Out of 72 patients, 41 received HMA+Ven as initial therapy and 31 received it in the R/R setting. Baseline characteristics are outlined in Table 1. Median age was 63 years for patients with R/R AML with 58% female. In the R/R cohort, ORR was 34.5% with 0 (0%) patients achieving CR, 8 (27.6%) patients achieving CRi, and 2 (6.9%) achieving MLFS (Table 2). When compared to patients receiving HMA+Ven as initial therapy, ORR was significantly lower in the R/R cohort (64.1% vs. 34.5%, p=0.03). Among 31 patients in the R/R cohort, 6.5% (n=2) proceeded to allogeneic stem cell transplant (allo-SCT) after achieving CRi. European LeukemiaNet (ELN) risk stratification was known in 22 patients in the R/R cohort and ORR were similar in patients in the favorable/intermediate risk group (n=8) compared to adverse risk group (n=14) (37.5% vs. 28.6%, p=1.0). When compared to HMA+Ven used as initial therapy, ORR among the R/R cohort were not different among adverse risk groups (58.3% vs. 28.6%, p=0.10); however, ORR were significantly lower among patients with favorable/intermediate risk (100% vs. 37.5%, p=0.009). At a median follow-up of 7.6 months (mo), mOS was 4.9mo in the R/R cohort with mOS among RES superior to NRES (not reached vs. 2.4mo, p=0.0009) (Figure 1). Moreover, mOS was inferior in R/R patients compared to initial therapy (4.9mo vs. 13.8mo, p=0.0013) (Figure 2). A total of 15 (48.4%) patients had HMA exposure prior to receiving HMA+Ven without apparent impact on mOS (3.7mo (prior HMA) vs. 4.9mo (no prior HMA), p=0.97). The median duration of CR/CRi was 5.2mo and the median time to CR/CRi was 2.4mo. Based on ELN risk groups, mOS was not statistically different among patients with favorable/intermediate risk disease compared to adverse risk disease (8.6mo (fav/int) vs. 2.8mo (adverse), p=0.07). Responses were also analyzed based upon somatic mutations (Figure 2). In patients with isocitrate dehydrogenase 1 and 2 mutations (IDH1/IDH2) compared to patients without IDH1/2, ORR were 60% vs. 25%, respectively (p=0.28) with no significant difference in mOS (7.2mo (IDHmut) vs. 3.1mo (IDHwt), p=0.38). Comparing patients with TP53 mutation to those without TP53 mutations, no significant difference in ORR (25% vs. 33%, p=1.0) or mOS (4.4mo vs. 6.9mo, p=0.0.84) was noted. Conclusion: Although combination therapy with HMA+Ven has yielded impressive responses as frontline therapy, response rates with this combination in the salvage setting are less encouraging with the possible exception of those patients with IDH1/IDH2 mutations. Nevertheless, responders to salvage HMA+Ven had a significant survival benefit compared to nonresponders, suggesting that this combination is a reasonable salvage option in patients with relapsed or refractory AML. Disclosures Padron: Incyte: Research Funding. Kuykendall:Incyte: Honoraria, Speakers Bureau; Celgene: Honoraria; Janssen: Consultancy; Abbvie: Honoraria. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet:Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services . Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Komrokji:JAZZ: Speakers Bureau; JAZZ: Consultancy; Agios: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy; Novartis: Speakers Bureau; Incyte: Consultancy. Sweet:Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: 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; Celgene: Speakers Bureau; Jazz: Speakers Bureau; Incyte: Research Funding; Pfizer: Consultancy; Stemline: Consultancy. Talati:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria; Celgene: Honoraria; Agios: Honoraria. OffLabel Disclosure: Venetoclax is approved in combination with hypomethylating agents (azacitidine or decitabine) or low dose cytarabine for treatment of newly diagnosed AML in adults aged 75 years or older, or those who have comorbidities that preclude the use of induction chemotherapy.

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