scholarly journals Real-World Observations and Practical Considerations of Subcutaneous Daratumumab Administration in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5018-5018
Author(s):  
E. Bridget Kim ◽  
Elizabeth O'Donnell ◽  
Andrew R. Branagan ◽  
Jill N. Burke ◽  
Cynthia C. Harrington ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Comparable Efficacy ◽  
Prior History ◽  
Rapid Infusion ◽  
Advisory Committees ◽  
Optimal Monitoring ◽  
Systemic Reactions ◽  
Patient Reported ◽  
History Of

Abstract Background: Subcutaneous daratumumab (dara-SC) has several advantages over intravenous daratumumab (dara-IV). It has significantly shorter administration time, lower rates of systemic reactions, and smaller administration volume, while maintaining comparable efficacy and safety. Its fixed dosing allows for easier preparation. At our institution, standard approach is to monitor for 4h following the initial dara-SC dose for those at high risk for systemic reactions, defined as no prior dara use, treatment break ≥90d, or any prior history of reactions. We also administer montelukast and fexofenadine for the first 2 doses of dara-SC in addition to the usual standard pre-medications. Herein, we share our experience with dara-SC use in both dara-naïve and dara-exposed patients in order to gain practical insight, such as optimal monitoring duration, considerations for transitioning between dara-IV and dara-SC, and the place of therapy for dara-IV based on adverse events (AEs). Methods: Between June 2020 and June 2021, patients who received at least one dose of dara-SC were identified and their record was reviewed for any systemic reactions, hypersensitivity medication use, and patient reported AEs. Results: Since June 2020, our dara-SC drug use increased from 38% to 91% of all doses. There were 208 patients who received at least 1 dose of dara-SC. Of 208 patients, 99 (47.6%) were dara-naïve and 109 (52.4%) had prior dara exposure - either transitioning from dara-IV on schedule or had dara-IV as a past line of therapy. We identified 124 patients who met the criteria for 4h post dara-SC injection monitoring: dara-naïve (79.8%), treatment break ≥90d (18.5%), or prior history of reactions (1.6%). Only 5 experienced systemic reactions, representing 4% among those at high risk. All reactions were mild requiring minimal intervention and occurred following the first dara-SC dose. Onset of reactions and type of intervention during the 4h monitoring window were: hypotension (2h; fluid), nausea/vomiting (2.5h; hypersensitivity medications), and sinus tachycardia (4h), while 2 patients had transient chest pressure/tightness at home (1 within 24h, 1 between 1-6d following the dose). Eleven patients (5%) receiving dara-SC converted back to dara-IV, with AEs being the most common reason. Diarrhea, fatigue, and injection site reactions were among the most frequent patient-reported AEs. When transitioning back to dara-IV, a 90min rapid infusion rate was used if >4 prior dara doses were given. No infusion-related reactions were observed. Conclusion: The introduction of dara-SC has significantly improved patient experience. We observed a lower rate of systemic reactions compared to previous reports of 10% with first dose of dara-SC. This may be partly due to our strengthened pre-medication strategy. Opportunities exist to further improve and apply practical considerations when administering dara-SC. Based on our results, shortening on-site monitoring time may be feasible. Disclosures O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Branagan: Adaptive: Consultancy; Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Yee: GSK: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy.

Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Samantha Ferrari ◽  
Chiara Pagani ◽  
Mariella D'Adda ◽  
Nicola Bianchetti ◽  
Annamaria Pelizzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Advisory Board ◽  
Advisory Committees ◽  
Risk Status ◽  
History Of ◽  
Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=<0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

B Cell Lymphoma In Association with Multiple Myeloma: Analysis of the Biologic Relationship

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1590-1590 ◽  
Author(s):  
Anuj K. Mahindra ◽  
Aliyah R. Sohani ◽  
Christiana E. Toomey ◽  
James S. Michaelson ◽  
Jeffrey A. Barnes ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Board Of Directors ◽  
Light Chain ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prior History ◽  
Advisory Committees ◽  
Age Of Diagnosis ◽  
History Of

Abstract Abstract 1590 Background: The occurrence of a secondary lymphoma in patients with a prior history of B-cell lymphomas has been reported.1, 2 There are few reported occurrences of Multiple Myeloma (MM) in patients (pts) with a prior history of lymphoma and the biologic relationship between the two neoplasms in such cases is unknown. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma and MM. Of the 4165 pts with B-cell lymphoma and 804 pts with MM, 6 pts with a history of B-cell lymphoma developed MM and 1 patient with a prior history of MM developed a B-cell lymphoma. We describe the morphology, immunophenotype, and clinical features of the 7 pts. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes and by light chain restriction. Results: There were 5 men and 2 women (median age of diagnosis of lymphoma, 65 years; median age of diagnosis of MM, 71 years). The pts with lymphoma included 2 pts with diffuse large B cell lymphoma, 2 pts with small lymphocytic lymphoma, 2 pts with follicular lymphoma and 1 patient with lymphoplasmacytic lymphoma. The development of MM was metachronous in 5 cases, following B-cell lymphoma by 3 years to 23 years and synchronous in 1 case. In 1 patient, the B-cell lymphoma developed 6 years after the diagnosis of MM. 6 pts achieved complete remission after treatment for lymphoma and 1 patient is ongoing treatment. 6 of the 7 pts required treatment for MM soon after diagnosis. 1 patient has smoldering MM and continues to be observed 57 months after diagnosis. FISH analysis indicated IgH rearrangement in 3 pts with MM; 1 patient with 17p deletion and monosomy 13; 3 pts had normal FISH and metaphase cytogenetics. In 3 pts, both neoplasms were kappa light chain restricted; in 1 patient both were lambda restricted; in 1 patient, the lymphoma was lambda light chain restricted while the MM was kappa light chain restricted and the reverse in another pt; in 1 patient the B-cell lymphoma was light chain negative and the MM was kappa restricted. IgVH rearrangement studies in 4 patients in whom tissue samples were available indicated that the two were clonally unrelated in 3 patients and related in only 1 patient. Conclusion: Clonality analysis of rearranged immunoglobulin genes from patients with both B-cell lymphoma and MM provide evidence of separate clonal origins of the two tumors in the majority of cases, thus excluding secondary transformation of the original B-cell clone. The presence or absence of a genetic predisposition to the development of multiple B cell malignancies requires further study.3 Disclosures: Off Label Use: The combination of lenalidomide and everolimue is an off label use in multiple myeloma. Abramson:Genentech: Consultancy; Novartis: Consultancy. Raje:Amgen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Research Funding.

scholarly journals A JAK2V617F Variant Allele Frequency Greater Than 50% Identifies Patients with Polycythemia Vera at High Risk for Venous Thrombosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 237-237
Author(s):  
Giuseppe Gaetano Loscocco ◽  
Paola Guglielmelli ◽  
Carmela Mannarelli ◽  
Elena Rossi ◽  
Francesco Mannelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Venous Thrombosis ◽  
Board Of Directors ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Advisory Committees ◽  
Free Survival ◽  
History Of ◽  
Independent Risk Factors

Abstract Background: Thrombosis is the main cause of morbidity and mortality in pts with Polycythemia Vera (PV). Current risk stratification is based on 2 variables: age >60y and history of thrombosis. Additional thrombotic risk factors in PV are generic cardiovascular risk factors and leukocytosis. JAK2V617F (JAK2VF) variant allele frequency (VAF) at diagnosis is highly heterogeneous. A VAF>75% was associated with higher rate of all thrombosis after diagnosis (Vannucchi AM et al, Leukemia 2007), and a VAF ≥ 60% correlated with increased rate of venous thrombosis (VT) in high-risk pts (Guglielmelli P et al, ASH 2018); however, predictive role of JAK2VF VAF is still debated. Aim: To evaluate the impact of JAK2VF VAF on rate of arterial and venous thrombosis in PV pts. Patients and methods: A cohort of 576 strictly 2016 WHO-defined PV pts followed at Univ. of Florence (1981-2020) were included. All pts were annotated for JAK2VF VAF, determined <3 years from diagnosis, and thrombosis at diagnosis and follow-up (FU). Arterial thromboses (AT) included stroke, transient ischemic attacks, retinal artery occlusion, coronary artery disease, and peripheral arterial disease; VT included cerebral venous thrombosis, deep vein thrombosis, pulmonary embolism. Splanchnic vein thromboses (SVT) were excluded. Only first occurring event was considered. Cox proportional hazard regression model was used for univariate and multivariable analysis. Kaplan-Meier (KM) analysis was used for time-to-event assessment, compared by log-rank test. Results: Median age was 61.4 y (range, 16.2-91.8), 58.2% were male; 62% were high-risk based on current classification. Median JAK2VF VAF was 41.5% (range, 0.3-100). A total of 76 (13.2%) pts had an AT event before/at PV diagnosis and 49 (8.5%) pts had an AT during FU. As regards VT, 64 (11.1%) and 39 (6.8%) pts had a VT before/at or after PV diagnosis, respectively. We found that JAK2 VAF as a continue variable was correlated with the risk of VT in FU (p=0.003) but not with AT (p=0.8). ROC analysis to determine the best cut-off level for JAK2 VAF predicting VT had an AUC of 0.72 and a best cut-off value of VAF=50%. VT at FU were significantly enriched in pts with VAF >50%: 14.5% versus 2.4%, p=<0.0001. VT -free survival (VT-FS) by KM was significantly shorter in the presence of a JAK2 VAF >50% (HR 4, CI 1.9-8.6, p<0.0001) (Figure 1A), whereas no difference was found for AT (HR 0.9). In addition to JAK2VF VAF>50%, univariate analysis for VT-FS identified history of VT (HR 2.9; CI 1.4-6.1, p=0.006), leukocytosis ≥11x10 9/L (HR 1.9; CI 1.1-3.4, p=0.02) and palpable splenomegaly (HR 1.9, CI 1-3.6; p=0.04) as risk factors. Multivariable analysis confirmed VAF>50% (HR 3.8, CI 1.8-8.1, p=0.0006) and previous VT (HR 2.4, CI 1.1-5.1; p=0.02) as independent risk factors for future VT. In contrast, univariate analysis for AT-free survival (AT-FS) identified history of AT (HR 2.5; CI 1.3-4.9, p=0.007), diabetes (HR 3.3; CI 1.6-6.5, p=0.0007), hyperlipidemia (HR 3.1; CI 1.7-5.6, p=0.0003) and hypertension (HR 2, CI 1.1-3.8; p=0.03) as predictors of future AT; age >60y showed only a trend (p=0.08). Multivariable analysis for AT-FS identified diabetes (HR 2.4, CI 1.2-5; p=0.02), hyperlipidemia (HR 2.3; CI 1.2-4.3, p=0.01) and previous AT (HR 2.1, CI 1-4.2; p=0.04) as independent predictors of future AT. Validation: Our findings were validated in an independent cohort of 315 2016-WHO defined PV pts from Policlinico Gemelli, Catholic Univ., Rome. After exclusion of 26 pts with SVT, analysis was conducted on 289 pts, 38 of them with thrombosis as heralding event (21 AT and 17 VT). Multivariable analysis confirmed JAK2VF VAF >50% (HR 2.3, CI 1.03-5.0, p=0.04) and previous VT (HR 4.5, CI 2.0-10.1; p=0.0003) as independent risk factors for future VT. In pts with VAF >50%, the rate of VT at FU was 19.9% vs 7.7%, P=0.005. KM curve showed that VT-FS was significantly shorter in pts with a JAK2VF VAF >50% (HR 2.2, CI 1.2-4.2; p=0.01) (Figure 1B). Of note, impact of JAK2 VAF>50% on VT at FU was statistically significant particularly in conventionally low-risk pts, accounting for an HR of 9.4 (CI 1.2-72) and HR 3.6 (CI 1.3-10) in Florence and Rome cohorts, respectively. Conclusions: These data support JAK2VF VAF as a strong independent predictor for future venous thrombosis in PV, in association with history of prior venous events, reinforcing that AT and VT are associated with unique risk factors in pts with PV. Supported by AIRC, Project Mynerva n.21267 Figure 1 Figure 1. Disclosures Vannucchi: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: 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; AbbVie: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Real-World Use of Therapeutic Anticoagulation in Patients with Paroxysmal Nocturnal Hemoglobinuria. Results of a Survey of Physicians in Australia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4537-4537
Author(s):  
Jeffrey Szer ◽  
Cecily J Forsyth ◽  
Anja Giese
Keyword(s):  
Board Of Directors ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Prior History ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Therapeutic Anticoagulation ◽  
Increased Risk ◽  
History Of

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematopoietic stem cell disorder characterized by uncontrolled complement-mediated hemolysis. Patients with PNH are at increased risk of thromboembolism and premature death. This risk is predominantly due to the effects of chronic hemolysis and platelet activation. Eculizumab, a monoclonal antibody that inhibits terminal complement activation, has been shown to reduce hemolysis and dramatically reduce the rate of thromboembolism. A previous publication (Kelly et al, 2011) suggested that cessation of therapeutic anticoagulation (TAC) in PNH patients on eculizumab with no prior history of thrombosis is safe. There are very few reports on the outcomes of cessation of TAC in PNH patients on eculizumab who have a prior history of thrombosis or on the use of non-vitamin K antagonist oral anticoagulant (NOAC) agents in PNH patients with a history of thrombosis. In Australia, patients with PNH are predominantly managed by individual hematologists rather than at a single centre and hence anticoagulation practices following the introduction of eculizumab therapy are variable. We surveyed Australian hematologists managing eculizumab-treated patients with PNH to obtain the details of anticoagulation management and incidence of thrombotic events in their patients. We received responses from 30 hematologists caring for a total of 58 patients with PNH on eculizumab (1-17 patients per hematologist) and the table summarises the results. TAC as primary prophylaxis had been ceased in 10 patients with no recurrent thrombotic events. One (1) patient remains on primary prophylaxis due to persistently high D-dimer and factor VIII levels. TAC for secondary prophylaxis had been ceased in 2 patients due to bleeding (1 patient with subdural hematoma, 1 patient with gastrointestinal bleeding) and neither of these patients had a further thrombotic event. One patient, with a prior history of thrombosis, requested cessation of TAC and subsequently developed a provoked thrombosis. Three patients not receiving TAC when eculizumab was commenced developed thrombosis; two (2) patients had provoked deep venous thromboses and one patient developed a splanchnic vein thrombosis following a cholecystectomy in association with severe sepsis. One patient had a portal vein thrombosis immediately prior to commencing eculizumab therapy but has never received TAC due to severe coexistent thrombocytopenia from myelodysplasia. This patient has not had a recurrent thrombosis. Three (3) patients with thrombotic events prior to eculizumab therapy (1 patient with pulmonary emboli, 1 patient with cerebral venous sinus thrombosis and 1 patient with inferior vena cava thrombosis) had anticoagulant therapy changed from warfarin to rivaroxaban. At a follow-up of at least twelve months for all 3 patients there have been no recurrent thrombotic events and no bleeding complications. In conclusion, these Australian data are consistent with those reported by Kelly suggesting that cessation of primary prophylaxis in PNH patients on eculizumab is safe. Cessation of TAC in PNH patients on eculizumab with a prior thrombosis can be considered if there are clear contraindications to anticoagulation. Thromboprophylaxis in situations of increased risk of venous thromboembolism remains essential for all PNH patients not on TAC, even when they are on eculizumab therapy. The three patients on rivaroxaban as secondary prophylaxis are, to our knowledge, the first reported patients with PNH treated on a NOAC. Table. Number of patients New thrombotic events Eculizumab treated 58 Ceased TAC: Total1. As 1o prophylaxis2. As 2o prophylaxis(i) Due to bleeding(ii) At patient request 1410431 -None-None1 (provoked) TE in patients not on TAC at commencement of eculizumab 3 3 (provoked) NOAC as 2o prophylaxis 3 None Disclosures Szer: Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Forsyth:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giese:Alexion: Employment.

scholarly journals Connect MM®—the Multiple Myeloma (MM) Disease Registry: Incidence of Second Primary Malignancies (SPM)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4749-4749
Author(s):  
Robert M. Rifkin ◽  
Rafat Abonour ◽  
Jatin J. Shah ◽  
Jayesh Mehta ◽  
Mohit Narang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Solid Tumor ◽  
Research Funding ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Prior History ◽  
Advisory Committees ◽  
History Of

Abstract Background: Increased rates of SPM have been observed as newer cancer treatments have improved survival over the past 2 decades (Fraumeni et al. NCI, 2006). Higher incidence of specific types of hematologic SPM following MM, especially acute myeloid leukemia and myelodysplastic syndromes, have been reported relative to the general population (Dores et al. NCI, 2006; Mailankody et al. Blood, 2011; Ravazi et al. Blood, 2011; Landgren and Mailankody. Leukemia, 2014). A complex interplay between myeloma-, host-, environmental-, and treatment-related factors likely contributes to the increased incidence of SPM in MM. Connect MM is the first and largest prospective, observational, US-based, multicenter registry designed to characterize patients (pts), treatment patterns, and outcomes in newly diagnosed MM (NDMM) pts. Methods: Between September 2009 and November 2012,a total of 1493 NDMM pts were enrolled from 234 US sites within 2 mos of the first diagnosis of MM. Patient data were collected at baseline and each subsequent quarter using a standardized form. Invasive SPM included hematologic and solid tumor second cancers and non-invasive SPM were defined as non-melanoma skin cancers (NMSC). SPM incidence and incidence rate (IR; number of pts with SPM per 100 patient-yrs [PY]) were calculated for all pts and by exposure to specific treatments, including lenalidomide (LEN). PYs were calculated as the observation period from the start of treatment until the detection of the first reported SPM (per category), death, or end of follow-up (pt lost or data cutoff). Results: As of Dec 10, 2013, SPM data were available for 1493 NDMM pts. The median age was 67 yrs (range, 24-94 yrs), 82% of patients were white and 57% were male. Median follow-up was 29.0 mos (0-49 mos). The median OS of treated pts was 44.4 mos. Fifty pts did not receive treatment and had no SPM reported. A total of 74 of the 1443 treated pts (5.1%) reported SPM. Invasive SPM were observed in 51 pts (3.5%): 37 pts (2.6%) with solid tumors and 14 pts (1.0%) with hematologic SPM. Lung/bronchus and myelodysplastic syndromes were the most frequently reported solid tumor and hematologic SPM respectively. NMSC were reported for 26 pts (1.8%). 3 pts had both an invasive SPM and NMSC. The IRs for invasive, hematologic, and solid tumor SPM by LEN exposure are listed in Table 1. By multivariate analysis, the only significant risk factor for the occurrence of SPM was prior history of invasive malignancy. Demographics (including age, ethnicity, race, and gender), International Staging System stage, family history of myeloma or other cancers, history of smoldering MM or monoclonal gammopathy of unknown significance, or prior radiation therapy were not associated with the occurrence of SPM. Conclusions: This analysis shows that there was no increased risk of invasive SPM in this disease-specific registry of pts with NDMM. The risk of SPM for LEN exposed pts was not greater than that for pts not exposed to LEN. In addition, multivariate analysis indicated the only significant risk factor for SPM was prior history of invasive malignancy. As additional agents are approved for the treatment of MM and the length of pt survival increases, longer prospective observation with expanded enrollment on the registry will better characterize the occurrence of SPM in this pt population. Correlations with risk factors including age, pre-existing MDS, risk status, as well as type and duration of therapy will continue to be investigated. Table 1. Incidence rates (per 100 PYa) by treatment exposure IR per 100 PY (95% CI) SPM LEN-Exposed (n = 977) Non–LEN Exposed (n = 466) Invasive 0.85 (0.61-1.19) 1.16 (0.72-1.86) Hematologic 0.17 (0.08-0.36) 0.47 (0.22-0.99) Solid tumor 0.67 (0.46-0.98) 0.68 (0.36-1.26) NMSC 0.50 (0.32-0.77) 0.41 (0.18-0.91) a PY of exposure is the sum of exposure of all pts. Disclosures Rifkin: Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Shah:Celgene Corp: Consultancy, Research Funding. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Lu:Celgene Corp: Employment. Kenvin:Celgene Corp: Employment. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Durie:Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees.

Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective. A Report From the International PNH Registry.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1525-1525 ◽  
Author(s):  
Petra Muus ◽  
Jeffrey Szer ◽  
Hubert Schrezenmeier ◽  
Robert A Brodsky ◽  
Monica Bessler ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Chest Pain ◽  
Board Of Directors ◽  
Disease Burden ◽  
Advisory Committees ◽  
Clone Size ◽  
The Past ◽  
Patient Reported ◽  
History Of ◽  
Equity Ownership

Abstract Abstract 1525 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis, a variable degree of bone marrow failure and thrombophilia, which may lead to reduced quality of life (QOL). There have been few reports of the disease burden of PNH from the patient's perspective. Aims: To describe patient-reported QOL, hospitalization, and missed work at time of PNH registry enrollment and to evaluate the association of these patient-reported outcomes (PROs) with demographics; patient reported symptoms (abdominal pain, chest pain and hemoglobinuria); and clinical characteristics (years since diagnosis, granulocyte clone size, underlying bone marrow disorder [BMD] and prior thrombotic event [TE]). Methods: Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry if they have a PNH clone regardless of clone size, other BMD, symptoms, or treatments. As part of the study, patients are asked to complete questionnaires at enrollment including the six subscales of the EORTC QLQ-C30 (range=0-100, higher scores better) and the FACIT-Fatigue scale (range=0-52, higher scores better). Patients are also asked “in the past 6 months have you been admitted to a hospital for your PNH” and “in the past 6 months did you miss work as a result of PNH” (questions about work were added later in the study). Statistical analysis used ANOVA and Chi-square tests as appropriate. Results: As of August 2010 there were 657 patients enrolled in the Registry. Of these, 377 (57%) patients completed a baseline questionnaire (BQ) and are included in this analysis. Patients with and without a completed BQ were comparable on most study variables, although patients with a higher clone size were less likely to complete a BQ. Patients had a mean age of 45.8±17.6 years; 54% were female. Median PNH (granulocyte) clone size was 75% (nearly two-thirds had a clone size ≥50%), 45% had BMD (mostly aplastic anemia) and 12% had history of TE. Abdominal pain in the last 6 months was reported by 45% of patients, chest pain by 28%, and hemoglobinuria by 64%. Mean EORTC scores (general population reference in parenthesis) were: global health=64.4 (71.2), physical functioning=79.7 (89.8), role functioning=73.9 (84.7), emotional functioning=76.0 (76.3), cognitive functioning=81.1 (86.1), and social functioning=77.2 (87.5). Thus, scores for PNH patients were decreased by about 10% in 4 of the 6 subscales. PNH patients had a mean FACIT-Fatigue score of 36.6, while a general population reference is 43.6 (or a 16% reduction). PROs were independent of time since diagnosis, PNH clone size, or underlying BMD. Males reported better physical, emotional, and social functioning and less fatigue than females (all p<.05). As expected, age strongly affected physical functioning (p<.01). Patients with prior TE reported worse global health, physical, role, cognitive functioning, and more fatigue than patients without prior TE (all p<.05). Patients reporting abdominal pain, chest pain, or hemoglobinuria had significantly worse EORTC and FACIT-fatigue scores on every scale (all p<.05). Overall, 26% of patients had a PNH-related hospitalization in the past 6 months. Patients who reported TE, abdominal pain, chest pain, or hemoglobinuria were more likely to be admitted to the hospital (all p<.05). There were 109 patients out of 244 (45%) who worked at a paid job. Of these,30% missed work in the past 6 months due to PNH. Patients were more likely to miss work if they had abdominal pain (47% vs 19%, p<.01 or hemoglobinuria (42% vs. 7%, p<.01). Conclusion: The disease burden to PNH patients is evident. Mean QOL is reduced in patients with PNH by 10 to 16% on most scales compared to the general population. One of four patients was hospitalized and 30% of patients with a paid job missed work due to PNH over a 6-month period. History of thrombosis and presence of PNH-related symptoms strongly affected QOL and hospitalization, while missed work was mostly impacted by symptoms. This global PNH Registry, which remains open to accrual ([email protected]), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment, including outcomes measured from the patient's perspective. Disclosures: Muus: Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. Bessler:Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy. Socié:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Urbano-Ispizua:Alexion: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Rosse:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kanakura:Alexion: Membership on an entity's Board of Directors or advisory committees. Khursigara:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell:Alexion Pharma International: Employment, Equity Ownership. Bedrosian:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals A Multicenter Phase II Single Arm Trial of Isatuximab in Patients with High Risk Smoldering Multiple Myeloma (HRSMM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3116-3116 ◽  
Author(s):  
Elisabet E. Manasanch ◽  
Sundar Jagannath ◽  
Hans C. Lee ◽  
Krina K. Patel ◽  
Connor Graham ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Plasma Cells ◽  
Infusion Reaction ◽  
Advisory Committees ◽  
Myeloma Cells ◽  
History Of ◽  
Smoldering Myeloma

Background High risk smoldering multiple myeloma (HRSMM), defined as having immunoparesis and at least 95% abnormal plasma cells/all plasma cells by advanced flow cytometry, has a risk of progression to multiple myeloma of about 75% after 5 years of diagnosis. These patient have no symptoms and current standard is to follow them without treatment. Isatuximab is an IgG1 monoclonal antibody that binds to CD38 highly expressed in myeloma cells. Isatuximab has activity as monotherapy (overall response rate (ORR) 35%), with lenalidomide/dexamethasone (ORR 56%) and pomalidomide/dexamethasone (ORR 62%) in relapsed MM. We designed a phase II study to test the efficacy of isatuximab in high risk smoldering myeloma. Our study is registered in clinicaltrials.gov as NCT02960555. Methods The primary endpoint of the study is the ORR of isatuximab 20 mg/kg IV days 1, 8, 15, 22 cycle 1; days 1, 15 cycles 2-6 and day 1 cycles 7-30 in high risk smoldering myeloma. 24 patients were accrued in the first stage (of maximum 61 patients). Secondary endpoints are PFS, OS, clinical benefit rate (CBR). Exploratory endpoints are quality of life analysis (QoL), MRD, molecular/immune characterization using DNA/RNA sequencing of myeloma cells and the microenvironment before and after treatment. Results 24 patients with HRSMM were accrued from 02/08/2017 until 12/21/2018 (Table 1). All patients are evaluable for response. Best responses: ORR (≥PR) 15(62.5%), CR MRD- flow at 10-5 1 (5%), VGPR 4 (17%), PR 10 (42%), minor response (MR) 4 (18%), stable disease 5 (21%); CBR (≥MR) 79%. Median number of cycles received were 11.5 (range 6-30). Five patients have stopped treatment (one has completed the study, one with heavy history of smoking was diagnosed with squamous cell cancer of the tongue, one could no longer travel to treatments due to relocation, two progressed to active multiple myeloma after 16 and 6 cycles of treatment, respectively). There have been no deaths. DNA/RNA seq is ongoing for biomarkers of response. There were 5 grade 3 severe treatment-related adverse events (RAE) which resolved to baseline: dyspnea -related to infusion reaction (n=2), headache (n=1), ANC decrease (n=1), urinary tract infection (n=1). Most common grade 1-2 related adverse events (n): nausea (7), vomit (5), WBC decrease (3), diarrhea (3), fatigue (6), headache (4), mucositis (4), myalgia (4) and infusion reaction (3). In patients with available QoL functional scores (n=9 at baseline and n=7 after 6 months of therapy), isatuximab was effective in reducing their anxiety and worry of progression to multiple myeloma. Isatuximab also improved general QoL scores by the end of cycle 6 of treatment which were now comparable to those in the general population (Figure 1). Conclusion Isatuximab is very well tolerated, results in high response rates in HRSMM and has the potential to change the natural history of this disease. In ongoing QoL analysis, initial data shows improvement in QoL and decreased cancer worry after isatuximab treatment. Immune-genomic analysis is ongoing and may identify patients that benefit the most from treatment. Disclosures Manasanch: celgene: Honoraria; merck: Research Funding; quest diagnostics: Research Funding; sanofi: Research Funding; BMS: Honoraria; Sanofi: Honoraria. Jagannath:Multiple Myeloma Research Foundation: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Medicom: Speakers Bureau; Merck: Consultancy. Lee:Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Patel:Poseida Therapeutics, Cellectis, Abbvie: Research Funding; Oncopeptides, Nektar, Precision Biosciences, BMS: Consultancy; Takeda, Celgene, Janssen: Consultancy, Research Funding. Kaufman:Janssen: Other: travel/lodging, Research Funding. Thomas:Xencor: Research Funding; BMS: Research Funding; Celgene: Research Funding; Amgen: Research Funding. Mailankody:Takeda Oncology: Research Funding; Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; CME activity by Physician Education Resource: Honoraria. Lendvai:Janssen: Employment. Neelapu:Acerta: Research Funding; Celgene: Consultancy, Research Funding; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Incyte: Consultancy; Merck: Consultancy, Research Funding; Allogene: Consultancy; Cellectis: Research Funding; Poseida: Research Funding; Karus: Research Funding; Pfizer: Consultancy; Unum Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Precision Biosciences: Consultancy; Cell Medica: Consultancy. Orlowski:Poseida Therapeutics, Inc.: Research Funding. Landgren:Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Abbvie: Membership on an entity's Board of Directors or advisory committees; Merck: Other: IDMC. OffLabel Disclosure: Isatuximab for the treatment of smoldering myeloma

scholarly journals Unmet Needs for Symptom Control in Essential Thrombocythemia with Front Line Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5175-5175
Author(s):  
Holly Geyer ◽  
Robyn M. Scherber ◽  
Heidi Kosiorek ◽  
Amylou C. Dueck ◽  
Jean-Jacques Kiladjian ◽  
...  
Keyword(s):  
High Risk ◽  
Blood Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Red Blood Cell Transfusion ◽  
Risk Scores ◽  
Advisory Committees ◽  
Transfusion Requirements ◽  
History Of

Abstract Background: Thrombotic and hemorrhagic complications are commonly encountered in uncontrolled essential thrombocythemia (ET). Both anagrelide and hydroxyurea (HU) have proven efficacious in cytoreduction as well as reducing these events and remain first line therapy for most high-risk ET patients. Independent of their role in risk-reduction, little is known about how these therapies impact patient symptomatology or quality of life. In this study, we compared the clinical and symptomatic profiles of ET patients receiving HU or anagrelide against patients with no previous experience with these agents. Methods: Data was assessed from a prospectively collected international database of ET patients in which demographics, disease features, and ET symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. ET risk scores were calculated using the IPSET scoring algorithm (Passamonti 2012). Thrombocytopenia was defined as a platelet count <100 x 10(9)/L, anemia was defined as hemoglobin<10 g/dL and leukopenia was defined as a white blood cell count <4.0 x 10(9)/L. Associations between the MPN-SAF individual symptoms were investigated using chi-square test for categorical data and ANOVA F-test for continuous variables. Results Hydroxyurea vs. HU Naive A total of 402 ET patients with active HU use were compared to 392 ET patients with no history of HU use. Patients using HU were older (63.5 years vs. 52.3 years, p<0.001) and had a greater concentration of both high risk (24.9% vs. 11.4%, p=0.001) and intermediate risk (53.9% vs 38.4%, p<0.001) patients. They also had a higher rate of prior thrombosis (29.8% vs 11.3%, p<0.001) and leukopenia (10.1% vs. 3.0%, p<0.001). No differences were noted between gender, a history of prior hemorrhage, red blood cell transfusion requirements, or the presence of anemia/thrombocytopenia. In comparing symptom profiles, no significant differences were noted between TSS or individual symptoms with the exception of slightly more severe cough in HU patients (1.5 vs. 1.1, p=0.02, Figure 1). Anagrelide vs. Anagrelide Naive A total of 49 ET patients with active anagrelide use were compared to 794 ET patients with no history of anagrelide use. Patients using anagrelide had a longer mean disease duration (8.1 years vs. 5.8 years) and were more anemic (9.1% vs. 1.2%, p<0.001). No differences were noted between age, gender, risk scores, the presence of leukopenia/thrombocytopenia, a history of prior thrombosis or hemorrhage complications or red blood cell transfusion requirements. Additionally, there were no significant differences between TSS or individual symptom items (Figure 1). HU vs. Anagrelide A total of 402 patients currently using HU were compared to 39 patients currently using anagrelide. Overall, HU users were slightly older (63.5 years vs. 55.1 years, p<0.001) with a greater population of patients meeting high risk criteria (24.9% vs. 2.8%, p=0.002) and having a history of prior thrombosis (29.8% vs. 12.8%, p=0.02). Patients receiving anagrelide had a slightly longer disease duration (8.2 years vs. 6.0 years, p=0.0446). In comparing symptom profiles, no differences were noted in TSS or individual symptom items between cohorts. Discussion In this retrospective analysis, it does not appear cytoreduction with either HU and/or anagrelide has a significant impact on ET symptom burden despite reducing vascular events. Importantly, the higher risk scores in HU patients did not translate directly into greater patient symptomatology supporting previous studies demonstrating a poor association between these two items. Prospective trials measuring ET symptom change, in the setting of randomized trials will better quantify impact of cytoreduction on symptom burden as well as quantify impact of newer agents such as interferon or jak inhibition. Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Disclosures Kiladjian: Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Takeda: 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, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Sanofi-Aventis: Consultancy; Novartis: Consultancy, Speakers Bureau; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding. te Boekhorst:Novartis: Consultancy; CTI Biopharma: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Myelofibrosis in Real Life: Findings from the French Intergroup of Myeloproliferative Neoplasms (FIM) Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3128-3128
Author(s):  
Brigitte Dupriez ◽  
Sylvie Chevret ◽  
Jean-Christophe Ianotto ◽  
Francoise Boyer ◽  
Pascale Cony-Makhoul ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Spleen Size ◽  
Biological Parameters ◽  
Advisory Committees ◽  
History Of

Abstract Background: Myelofibrosis (MF) is the less frequent Philadelphia-negative myeloproliferative neoplasms (MPN). We have included in a nationwide database primary (P), post-polycythemia (PPV) and post-essential thrombocythemia (PET) MF diagnosed in France since 2005. Methods: Inclusion criteria were: diagnostic of MF after 2005; according strictly to WHO (bone marrow biopsy mandatory); informed consent. The registry was launched in Oct. 2013, and 26 hematology centers included patients (pts). Summary statistics were reported, namely median [Interquartile range, IQR] or percentage. Baseline characteristics were compared across IPSS groups using chi-square test or Mann and Whitney test. Kaplan-Meier survival curves were plotted and compared by the log-rank test. Results: At time of analysis (June 2016) a total of 527 pts were included in the registry, complete baseline data were available in 499 (95%), and follow-up (FU) data in 433 (87%). Median [IQR] age and M/F sex ratio were 71 [63-78] years and 315/184 (1.7), respectively (resp). 301 (60%) pts had PMF, 182 (36%) had secondary MF (including 64 PPVMF and 118 PETMF) and 16 had pre-fibrotic MF. Five percent of pts had a familial history of hematologic malignancy, and 22% a history of thrombosis or hemorrhage. Splenomegaly was present in 386 (77%) with a median [IQR] spleen size of 4 cm [1-8] below costal margin, and was symptomatic in 11% of pts. Constitutional symptoms were present in 107 (21%) (weight loss in 56, night sweats in 61, fever in 14), and ECOG score was 0, 1, 2, and 3 in 53%, 36%, 11% and 0.3% of pts, resp. Median [IQR] Hemoglobin, WBC and platelet counts were 109 g/L [94-122], 9.3 G/L [5.7-16.0] and 257 G/L [138-430], resp. Circulating blast cells were present in 41%, LDH was above normal value in 95% of pts, median EPO level was 54 [11 - 57] U/L. Grade of fibrosis (WHO) was 1, 2, and 3 in 2%, 66% and 32% of pts, resp. Karyotype was done in 321 pts, normal in 173 (54%), abnormal with favorable prognostic value in 89 (30%) and unfavorable in 30 (10%) (29 failures). A total of 461 (92%) pts had molecular testing: 60% were JAK2V617F positive, 4% had MPL and 7% had CALR mutations, and 99 (28%) over the 352 pts with triple testing were triple negative. IPSS risk categories were low, int-1, int-2 and high in 68 (14%), 168 (34%), 158 (32%), and 105 (21%) pts, resp. In addition to constitutional symptoms, there was a significant increase in the prevalence of clinical signs across IPSS categories (from low to high risk): symptomatic spleen (p=0.016) -though no difference in spleen size was found (p=0.18)-, early satiety (p=0.013), ECOG score (p= 0.0001), bone pain (p=0.002). Moreover, among biological parameters, there was an increase across IPSS groups in WBC (p=0.029), LDH (p=0.0007), ferritin (p=0.003), circulating CD34+ cells (p=0.020), EPO level (p=0.035). In contrast, a decrease was seen for hemoglobin and platelets (p=0.0001 for both). Lastly, frequency of grade 3 fibrosis increased with IPSS (p=0.043), while no evidence of difference was found regarding abnormal karyotype and mutational pattern. Median FU was 33 months [9-63 months]. Among those 433 pts with FU data, median FU was 38 months [19-68], and 124 (29 %) pts had died at the time of analysis, including 13%, 17%, 31%, and 40% of pts from the Low, Int-1, Int-2, and High risk groups, resp (p= 0.0001, figure 1). In the 450 pts with treatment data, treatments received during FU included cytoreductive drug (41%), Jak-inhibitors (35%), Interferon alpha (18%), IMIDs (4%). Splenectomy was performed in only 14 (3%) pts. Forty percent of pts received packed red blood cells, and 12% platelets transfusions. 49 (11%) patients participated in a clinical trial, and 27 (6%) were allografted. Conclusion: This is the first analysis of the French MF observatory after inclusion of more than 500 pts diagnosed and treated during the past 10 years. Complete baseline data and follow-up information available for the majority of pts should allow for new studies of outcomes and influence of clinical and biological parameters, as well as reassessment of prognostic models in the era of new targeted therapies. Figure 1 Comparison of overall survival according to IPPS Figure 1. Comparison of overall survival according to IPPS Figure 2 Figure 2. Disclosures Etienne: Pfizer: Speakers Bureau; BMS: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Ugo:Novartis: Membership on an entity's Board of Directors or advisory committees. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT, Consolidation with Krd and Maintenance with Rd

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 781-781 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Joaquin Martinez-Lopez ◽  
Paula Rodriguez Otero ◽  
Veronica Gonzalez-Calle ◽  
Marta Sonia Gonzalez ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Skin Rash ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Second Primary ◽  
Advisory Committees ◽  
End Point ◽  
Patient Reported ◽  
Risk Of Progression

Introduction: SMM is an asymptomatic and heterogeneous plasma cell disorder. Both Spanish Myeloma and ECOG Groups have demonstrated that pts at high risk of progression to active MM benefit from early treatment with R-based regimens. Our next step was to design this phase 2, single arm trial, focusing on the same population, but with the potential goal of cure, defined by sustained minimal residual disease negativity (MRD-ve) at 5 years after HDT-ASCT. Patients and methods: Ninety SMM pts at high-risk of progression (&gt;50% at 2 yrs), younger than 70 years and transplant candidates were included. The high risk was defined by the presence of both ≥PC 10% and MC ≥3g/dL (Mayo) or ifonly one criterion was present, pts must &gt;95%of aberrant PCs within the total PCsBM compartment by immunophenotyping plus immunoparesis (Spanish). Induction therapy consisted on six 4-weeks cycles of KRd in which K was given at dose of 36 mg/m2 twice per week plus R at dose of 25 mg on days 1-21 and dexamethasone at dose of 40 mg weekly. Melphalan at dose of 200 mg/m2 followed by ASCT was given as intensification therapy followed by two KRd consolidation cycles and maintenance with R at dose of 10 mg plus dexamethasone at dose of 20 mg weekly for up to 2 yrs. The primary end-point was to evaluate the MRD-ve rate by next generation flow (NGF) after induction and ASCT and our aim was to increase the MRD -ve rate from 34% (reported in NDMM pts after VTD and ASCT) to at least 50%. Results: Between June 2015 and June 2017, 90 high-risk SMM pts were recruited. Twenty-eight pts (32%) shared at least one of the new biomarkers predicting imminent risk of progression to MM. On February 4th, 2019, 71 pts were already receiving maintenance treatment; 7 pts had finalized the treatment and there were 11 early discontinuations (4 biochemical relapses during maintenance, 2 Informed Consent refusal, 3 adverse events and two deaths). After a median follow-up of 32 months (8-128), 93% of pts remain alive and free of progression and 98% of them alive. In the intent-to-treat pts' population, after induction, the ≥CR rate was 41% and increased to 59% after HDT-ASCT and to 70% after consolidation. In the same analysis, MRD-ve rate was observed in 30% of pts after induction, 52% after HDT-ASCT and 57% after consolidation. If we focus on the 83 pts who completed induction, HDT-ASCT and consolidation, the ≥CR/undetectable MRD rates were 42%/31%, 64%/56% and 76%/63% after each step, respectively. Concerning toxicity, during induction, G3-4 neutropenia and thrombocytopenia were reported in 5 (6%) and 10 pts (11%), respectively. G3-4 infections were reported in 16 pts (18%), followed by skin rash in 8 pts (9%). One patient reported G1 atrial fibrillation and another cardiac failure secondary to respiratory infection. Three pts reported hypertension (G2 in two and G3 in one). In all but two of the pts, PBSC collection was successful with a median of 4.10 x 106/Kg CD34 cells collected. All pts engrafted but one patient developed late graft failure. During consolidation, 2 pts developed G3-4 neutropenia, 3 pts G3-4 infections and 1 pt skin rash. Maintenance treatment is ongoing and one patient had to discontinue due to a second primary malignancy (lung cancer) and other due to sustained thrombocytopenia. Conclusions: The primary end point of the trial was met, and 56% of the pts who completed induction and HDT-ASCT achieved MRD-ve. This "curative strategy for high risk SMM" continues being encouraging and 93% of pts remain alive and progression-free at 30 months and 98% of pts alive. Disclosures Mateos: GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodriguez Otero:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; Takeda: Consultancy; BMS: Honoraria; Kite Pharma: Consultancy. Oriol:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy; Takeda: Consultancy, Speakers Bureau; Celgene Corporation: Consultancy, Speakers Bureau. Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rosinol Dachs:Janssen, Celgene, Amgen and Takeda: Honoraria. Amor:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Puig:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; The Binding Site: Honoraria. De La Rubia:AMGEN: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. De Arriba:Takeda: Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lopez Jimenez:GILEAD SCIENCES: Honoraria, Other: Education funding. Ocio:Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Mundipharma: Research Funding; AbbVie: Consultancy; Sanofi: Research Funding; Seattle Genetics: Consultancy; Array Pharmaceuticals: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Pharmamar: Consultancy. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria.

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