scholarly journals Improved Treatment Outcomes for Patients with Hodgkin Lymphoma Relapsing after Autologous Hematopoietic Stem Cell Transplantation in the Brentuximab Vedotin Era - the Real-Life Report from the Polish Lymphoma Research Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5276-5276
Author(s):  
Anna Czyz ◽  
Anna Lojko-Dankowska ◽  
Agnieszka Giza ◽  
Monika Dlugosz-Danecka ◽  
Wojciech Jurczak ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Salvage Treatment ◽  
Study Group ◽  
Advisory Committees ◽  
Historical Group ◽  
Group 2 ◽  
Group 1

Background Brentuximab vedotin (BV) is an effective salvage treatment in patients with relapsing/progressive Hodgkin lymphoma (HL). However, it is unclear how much BV improved the outcome of BV naïve patients who relapsed after autologous hematopoietic stem cell transplantation (autoHCT) in real life. To address this question, we compared the outcome of patients who received conventional salvage treatment before the BV era to those who were treated with BV in haematological centres allied within the Polish Research Study Group. The goals of the study were to compare: the response rates to the conventional salvage chemotherapy and to the BV-based treatment, the proportion of patients proceeding to subsequent allogeneic (allo) or second autologous HCT and finally the overall survival (OS), and progression-free survival (PFS) of relapsing patients after autoHCT treated with and without BV. Methods and study group The study group consisted of adult patients with classical HL relapsing after first autoHCT who were treated either with conventional salvage chemotherapy (between 2001 and 2013; Group 1, n=121) or BV based treatment (between 2012 and 2018; Group 2, n=44). The groups did not differ in terms of age or gender. The patients in Group 2 received more chemotherapy lines before post-transplant salvage treatment (median 3, range 1-6) compared to those in historical Group 1 (median 2, range 1-6) (p=0.013). No patient was treated with immune check points inhibitors. The response to salvage treatment in the majority of patients in historical Group 1 was assessed with conventional computer tomography (CT), while in all patients in Group 2 with CT combined with positron emission tomography. Results The rate of the objective response rate defined as the complete or partial response was higher in Group 2 (84% vs 60%, p<0.001). Of a total of 121 patients in Group 1, 34 (28%) proceeded to the second autoHCT, and 27 (22%) to alloHCT, compared to 4 (9%) and 20 (45%) of 44 patients in Group 2, respectively (p=0.004). The median follow-up time of survivors is longer in the historical Group 1 compared to Group 2 (40 months vs 19 months, p <0.001). However, at 2 years after the start of post-transplant salvage treatment, the estimated OS for patients in Group 1 was 55.2 % (95 % CI 45.8-64.3 %) compared to 81.9 % (95 % CI 66.5-91.2 %) for patients treated with BV (p=0.009) (figure). The respective estimated 2-year PFS was 41.2% (95 % CI 32.3-50.8 %) for Group 1 and 56.2% (95 % CI 38.5-72.4 %) for Group 2 (p=0.038). Importantly, the OS of patients who proceeded to alloHCT after BV-based salvage treatment was statistically significantly better compared to patients treated with alloHCT in the historical pre-BV group (2-year OS 81% vs 55%, p< 0.001). Conclusions In the era of brentuximab vedotin, significantly more patients with HL relapsing after autoHCT achieve objective response and proceed to allogeneic HCT. This most likely translates to the better PFS exceeding 24 months and most importantly to the significantly better OS of patients treated with BV compared to those treated with conventional salvage chemotherapy in the pre-BV era. Figure Disclosures Czyz: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Macrogenomics: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Roche: Research Funding; Servier: Research Funding; MorphoSys: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Celtrion: Research Funding. Walewski:Gilead: Other: Travel Expenses; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wrobel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaucha:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Patient-Specific Risk Factors Independently Influence Survival in Myelodysplastic Syndromes in an Unbiased Review of EHR Records

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5440-5440
Author(s):  
Travis Spaulding ◽  
Nicholas Strayer ◽  
Andrew Sochacki ◽  
Shannon Stockton ◽  
Alexander Silver ◽  
...  
Keyword(s):  
Risk Factors ◽  
Board Of Directors ◽  
Research Funding ◽  
Health Record ◽  
Comorbid Conditions ◽  
Comorbid Disease ◽  
Advisory Committees ◽  
Study Population ◽  
Group 2 ◽  
Group 1

Background: Myelodysplastic syndromes (MDS) are clonal hematologic neoplasms stratified by risk by the international prognostic scoring system (IPSS) and IPSS-revised (IPSS-R) which measure risk by morphologic dysplasia, clinical cytopenias, blast count, and cytogenetic abnormalities. (PMID: 9058730, 22740453) The IPSS/IPSS-R do not consider clinical comorbid conditions, though MDS patients with higher burden of comorbid disease have higher rates of non-leukemic death, particularly those with cardiovascular and pulmonary disease. (19324411) Despite this, there has been limited investigation into how specific comorbid conditions may help define subgroups of patients with MDS. Methods: We identified 2676 cases of MDS as defined by ICD-9 code (238.72 - 238.75) in Vanderbilt's Synthetic Derivative (SD). The SD is a de-identified electronic health record (EHR) of over 2.2 million patients with a companion biorepository of DNA (BioVU) for a subset of these patients, including all of the patients with MDS. The 2676 cases were matched by age, gender, race, burden of comorbidities in EHR, and age at last appointment in EHR with 5287 controls. ICD-9 codes for other myeloid disease (e.g., myeloproliferative neoplasms, acute myeloid leukemia) or history of hematopoietic stem cell transplant were excluded among the controls. Characterization of comorbidities, via phecode analysis, was conducted on all cases and controls. Phecodes are groups of related ICD-9 codes describing a clinical syndrome or medical problem, previously demonstrated to be useful in phenome-wide associated studies in EHRs. (28686612) A case was defined as having a phecode only if a representative ICD-9 code was present on two distinct days in the EHR. Next, a cluster analysis of the study population and their associated comorbidities, via a bipartite stochastic block model, was completed, and the study population was organized into hierarchical structure based upon the similarities in comorbidity patterns among patients. Results: ICD-9 codes from the study population made up 181 phecodes, which were found in hierarchical cluster analysis to further cluster into 54 sub-groups and 16 larger groups. MDS patients clustered throughout all groups, the majority of which contained control patients; yet some MDS cases sub-clustered into groups that included a majority of MDS cases and these were further analyzed. Notably, two groups had equivalent size and MDS status were found to have significant differences in phecode profiles. Group 1 had 795 total patients with 783 MDS cases (98.5%) and Group 2 had 769 total patients with 684 MDS cases (88.9%), as per Fig 1a. There were no significant difference in sex between the two groups. Group 1 patients were significantly younger than Group 2 patients (58.3y vs 62.9y; p = 1.36 x 10-7), yet tended have increased risk of renal, cardiovascular and thromboembolic disease than Group 2, as per Fig 1b. Additionally, a higher proportion of Group 2 patients (695/769 or 90.4%) were alive at time of data extraction than Group 1 patients (451/795 or 56.7%) (OR 4.51, p = <2.2 x 10-16). Conclusions: By performing a phenome-wide analysis of patients with MDS in a large electronic health record (EHR), we reveal specific subgroups of MDS patients with distinct comorbidities and different survival, not affected by age or sex. This study demonstrates the ability to study comorbid conditions of MDS patients in an unbiased fashion, independent of disease specific risk factors that inform IPSS-R and which have historically been most important in stratifying risk in MDS. The role of comorbidity is instinctually clear to the adroit clinician, and this technique could provide distinct comorbid disease patterns which impute risk, or perhaps etiology in MDS. Disclosures Savona: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Patents & Royalties; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Exploration of Survival Stratification of Patients with Multiple Myeloma after First Relapse Using Real World Data

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2417-2417 ◽  
Author(s):  
Roman Hájek ◽  
Jiri Jarkovsky ◽  
Walter Bouwmeester ◽  
Maarten Treur ◽  
Lucy DeCosta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Treatment Decision ◽  
Advisory Committees ◽  
Patient Risk ◽  
First Relapse ◽  
Survival Expectations ◽  
Group 2 ◽  
Group 1

Abstract Risk stratification tools in multiple myeloma (MM), such as the International Staging System (ISS) and the revised-ISS (R-ISS), have improved understanding of survival expectations using the strongest known predictors at time of diagnosis. Given their value at diagnosis, these have been used to define risk after first relapse in clinical trials and standard practice. Although these tools have not been validated in this setting, their use arises because of the need to better characterize patients in order to define survival expectations and treatment decisions. Once the patient has relapsed, there are additional variables that may need to be considered in order to systematically assess patient risk, understand drivers of disease progression and ensure that treatment strategies are aligned with patient risk. Using data from the Czech Registry of Monoclonal Gammopathies (RMG), this study assessed predictors of overall survival (OS) and developed a new Risk Stratification Tool (RST) to predict OS at time of treatment decision after first relapse (TTD1). The RST was developed by estimating the strongest predictors of OS at both diagnosis and TTD1 to define the final parameters for inclusion. The cut-offs for each parameter reflect conventional cut-offs used in clinical practice and some were supported by evidence using a K-adaptive Partitioning for Survival (KAPS) approach, which stratified data based on distinct survival expectations. The hazard ratio (HR) of the selected predictors was used to assign a score per parameter at a patient level where missing data were entered with a contribution equal to 1. Using the full RMG data set at TTD1 (N=1418) the (KAPS) method was run to define 4 distinct group of patients based on survival expectations. The RST consists of 4 dimensions and 12 item questions based on the strongest predictors of survival at TTD1, "Patient Factors" (age and Eastern Cooperative Oncology Group (ECOG) performance status), "Existing Stratification Factors (R-ISS at diagnosis and ISS at TTD1), "Disease Factors" (calcium level, number of bone lesions, extramedullary disease, thrombocyte count, clonal cells in bone marrow aspiration cytology, lactate dehydrogenase [LDH]) and "Treatment history" (refractory to prior therapy, time-to-next-treatment [from initiation of treatment of first anti-myeloma drug to initiation of treatment at first relapse]) (Table 1). Subsequently, we explored each group based on distribution of frailty-driven measures (age and ECOG) and aggressiveness of the disease (rest of parameters) to understand what is driving stratification. Figure 1 shows the KM curve of survival after TTD1 for each of the 4 groups estimated by KAPS. The new analysis shows strong differentiation in survival expectations between the 4 groups (Table 2), showing significantly different OS for all groups compared with reference. The median OS and Confidence Intervals per group did not overlap, supported by the positive association of HR across groups. The distribution of the Total Score (Figure 2) is between 1 and 2, which shows sufficient sensitivity to differentiate these groups by survival expectations. The RST can then be split into Frailty Score and Aggressiveness Score (Figure 3a & b) to understand what is driving disease severity. The distribution of these two scores shows that group 1 consists of low patient frailty and low disease aggressiveness, whereas group 4 shows high on both elements. Group 2 has an increased score for frailty and marginal increase in aggressiveness compared with group 1, and group 3 stratification is driven by an increase in aggressiveness over group 2. The analysis showed that predictors, patient's experience of prior treatment and level of disease impact at the point of treatment decision after first relapse provided an initial framework to demonstrate strong differentiation between groups based on patient severity and what is driving patient risk (patient frailty vs aggressiveness of disease). The RST has shown promising results when applied to the RMG, however further validation of this work is required using other real-world and clinical trials data. Nevertheless, this analysis is a first step in systematically assessing patient risk to improve the selection of treatments based on improved understanding of patient profiles. Disclosures Hájek: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; BMS: Honoraria; Takeda: Consultancy; Celgene: Consultancy, Research Funding. Bouwmeester:Amgen: Consultancy. Treur:Amgen: Consultancy. DeCosta:Amgen: Employment, Other: Holds Amgen Stock. Campioni:Amgen: Employment, Other: Holds Amgen Stock. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Raab:BMS: Consultancy; Celgene: 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: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Schoen:Amgen: Employment, Other: Holds Amgen Stock. Szabo:Amgen: Employment, Other: Holds Amgen Stock. Lucie:Amgen: Consultancy. Gonzalez-McQuire:Amgen: Employment, Other: Holds Amgen Stock.

RAEB-1 with Erythroid Hyperplasia and Erythroleukemia Share Clinico-Biological Features and Outcome: A Same Disease with Different Labels?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2866-2866
Author(s):  
Xavier Calvo ◽  
Leonor Arenillas ◽  
Mar Tormo ◽  
David Valcárcel ◽  
Elisa Luño ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
De Novo ◽  
Erythroid Cell ◽  
Advisory Committees ◽  
Biological Features ◽  
Erythroid Hyperplasia ◽  
Group 2 ◽  
Group 1 ◽  
Who 2008

Abstract Introduction: Based on the 2008 World Health Organization classification (WHO 2008), erythroleukemia is defined by the presence of ≥50% erythroid precursors in bone marrow (BM) and ≥20% myeloblasts in the non-erythroid cell population. Multilineage dysplasia is almost always present with high rates of MDS-like cytogenetic abnormalities, specially complex karyotypes. Therefore an extensive comparison with myelodysplastic syndromes (MDS) with ≥50% erythropoesis seems crucial to elucidate whether erythroleukemia and MDS with erythroid hyperplasia should be considered as different biological entities. Aim: To elucidate this issue, the outcome and cytogenetic alterations of erythroleukemia patients were studied and compared to MDS patients with ≥50% erythropoesis with <5% BM blasts (RA, RARS, CRDM, MDS-U) or those with ≥5%-<10% (RAEB-1). In this subset of patients, the diagnosis of RAEB-2 is not possible because those with ≥50% erythropoesis and ≥10% BM blasts were formally diagnosed with erythroleukemia when the blast percentage was assessed in the non-erythroid cell population. Methods: We retrospectively analyzed 448 de novo MDS with ≥50% erythropoesis and 59 de novo erythroleukemias from the MDS Spanish registry (RESMD). Diagnosis was done according to WHO 2008 and patients with ≥80% erythropoiesis with less than 20% of myeloblasts in the non-erythroid cell compartment were excluded assuming a diagnosis of pure erythroid leukemia. Results: Median age of presentation was 74 years (25-94 years), median follow-up was 29.4 months, 63% were males. Median overall survival (OS) of MDS patients with ≥50% erythropoiesis and <5% of BM blasts (n=389; group-1) was significantly longer than MDS with ≥50% erythropoiesis and ≥5%-<10% (n=59; group-2/RAEB-1) (69 months vs. 18 months, p <0.001). Although erythroleukemia patients (n=59) presented a shorter median OS than group-1 patients (69 months vs. 14.5 months, p <0.001), there was no significant differences compared to group-2 patients (RAEB-1) (18 months vs. 14.5 months, p =0.679). Figure 1. Percentage of abnormal karyotypes was significantly higher in the group-2 and EL vs. group-1 but there was no significant differences between group-2 and erythroleukemia (56.9% vs. 44.1%, p =0.165). Moreover no significant differences were observed in the percentage of high-risk karyotypes defined by the IPSS (complex karyotype, chromosome 7 abnormalities) between RAEB-1 and erythroleukemia (30.5% vs. 23.7%, p =0.408). Finally, the presence of a high-risk IPSS karyotype was capable to discriminate two risk groups in the subset of patients with ≥5% BM blasts (RAEB-1 and erythroleukemia). Figure 2. Conclusion: Erythroleukemia and RAEB-1 with ≥50% erythropoiesis share clinico-biological features and outcome. Our findings suggest that erythroleukemia is a continuum of MDS with erythroid hyperplasia and karyotype rather than an arbitrary blast cut-off is the main prognostic marker in this subset of patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Valcárcel: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Díez-Campelo:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Janssen: Research Funding. Ramos:GlaxoSmithKline: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria.

scholarly journals Acute Myeloid Leukemia with Myelodisplasia-Related Changes (AML-MRC) Defined Only By Morphological Findings May Not Represent a Poor Prognosis AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2612-2612
Author(s):  
Ana Pérez ◽  
Olga Salamero ◽  
Helena Pomares ◽  
Maria Julia Montoro ◽  
Montserrat Arnan Sangerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Poor Prognosis ◽  
Advisory Committees ◽  
Group 3 ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

According to the 2016 WHO classification, AML-MRC encompasses an heterogeneous group of acute myeloid leukemias (AML) comprising: AML emerged from a previous myelodysplastic syndrome (MDS) or myeloproliferative /myelodysplastic disease (group 1), AML with MDS-defining cytogenetic abnormalities (group 2), or acute myeloid leukemia (AML) with dysplasia in at least 2 cell lineages without the above mentioned (group 3). In spite that AML-MRC has been considered a high-risk entity with poor prognosis, little is known on the relationship of clinical and biological characteristics with outcomes in these three groups. The aim of this study was to describe the clinical and biological characteristics of patients with AML-MRC and analyze their prognostic variables and outcomes. We retrospectively analyzed AML-MRC cases diagnosed between January-2009 and December- 2018 in two institutions. Descriptive variables were studied to compare the three AML-MRC groups. AML cytogenetic risk and response were defined according to the European Leukemia Net recommendations. Overall survival (OS) was considered as the time from the diagnosis to the last visit. Survival analysis were performed with Kaplan Meier method and comparisons with the log-rank test. Among 575 cases of AML identified, 186 (32.3%) met AML-MRC criteria and were included in the study. The main patient characteristics are shown in Table1. Median age was 72 (range, 22-88) years and 32% were female. Adverse karyotype was present in 29% of patients, being more prevalent in the AML-MRC group 2. Sixty one patients (33%) received an intensive chemotherapy approach and 36 (19%) an allogeneic stem cell transplantation. Patients in group 3 exhibit a higher probability of achieving a complete response than groups 1 and 2 (Table 2). After a median follow-up for survivors of 28.5 months (range, 5-130), 149 (80%) died in this period. Three years Overall Survival (OS) for patients in groups 1, 2 and 3 was 3 (0-117), 5 (0-93) and 10 (0-130) months, respectively (p=0.012) (Figure 1). Type of treatment (intensive, non intensive or best supportive care) and cytogenetic risk also showed impact on OS. Multivariant analysis adjusting these factors showed that patients in group 3 also presented better OS than patients in group 1 (HR=0,42 [IC95% 0,18-0,84], p=0,02), both with around a 30% of patients with adverse cytogenetics. To conclude the present study suggests that group 3 of AML-MRC, for which the diagnosis is based solely on morphologic findings, showed better prognosis than the other groups. A more detailed molecular characterization might contribute to improve prognostic stratification of this heterogeneous AML entity, particularly in patients with non-high risk cytogenetics. Disclosures Salamero: Pfizer: Honoraria; Daichii Sankyo: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Valcárcel:Jazz Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: spouse is an employee in the company, Speakers Bureau; Pfizer: Honoraria. Bosch:AstraZeneca: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Significance of Degree of HLA Disparity When Using Haploidentical Donors with T-Replete PBSC and Post-Transplantation Cyclophosphamide (PTCy) in Acute Myeloid Leukemia (AML) in First Complete Hematologic Remission (CR1)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3910-3910
Author(s):  
Mohamed A. Kharfan-Dabaja ◽  
Myriam Labopin ◽  
Ernesto Ayala ◽  
Ali Bazarbachi ◽  
Didier Blaise ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hazard Ratio ◽  
Advisory Committees ◽  
Group 2 ◽  
Hla Mismatches ◽  
Group 1

Abstract Background: Haploidentical allogeneic hematopoietic cell transplantation (haplo) has expanded applicability of the procedure to patients for whom a suitable HLA compatible donor was not available in the past. A small multicenter retrospective study of 185 patients with hematologic malignancies who received a nonmyeloablative preparative regimen followed by infusion of bone marrow (BM) hematopoietic cells from haploidentical donors showed no significant association between the number of HLA mismatches (HLA-A, -B, -C, and -DRB1 combined) and risk of acute grade 2-4 graft-versus-host disease (GVHD) (hazard ratio [HR]=0.89; P=0.68 for 3-4 mismatches vs fewer antigen mismatches). This haploidentical transplant platform has certainly evolved. Nowadays, G-CSF mobilized peripheral blood stem cells (PBSC) are commonly used owing to its increased convenience vis-à-vis performing a BM harvest. Study population: Here, we evaluate post transplant outcomes when using haploidentical donors with T-replete PBSC and PTCy in AML in CR1. A total of 494 patients (4/8 HLA mismatch (group 1)=360, 2-3/8 HLA mismatch (group 2)=134) underwent the procedure at an EBMT participating center. The primary endpoints were cumulative incidences of grade 2-4 acute GVHD and chronic (all grades) GVHD. Secondary endpoints included cumulative incidence of relapse (RI), non-relapse mortality (NRM), leukemia-free (LFS) and overall survival (OS) and GVHD-free relapse-free survival (GRFS). Results: Group 1 and group 2 were not statistically different in regards to median age at allografting (54.1 vs. 56.1 years, p=0.51), median year of haplo transplantation (2018 vs. 2018, p=0.36), incidence of de novo AML (86.4% vs. 88.1%, p=0.63), Karnofsky equal or more than 90 (77.5% vs. 79.1%, p=0.70), and use of myeloablative conditioning (MAC) (44.7% vs. 48.5%, p=0.45). Patients in group 1 had a longer time from diagnosis to haplo-transplantation (5.3 vs. 4.9 months, p=0.03). In multivariate analysis, group 1 and group 2 did not differ in cumulative incidence of grade 2-4 acute GVHD (Hazard ratio (HR)=0.89 (95%CI=0.62-1.26), p=0.51) but group 1 had a significantly higher incidence of chronic (all grades) GVHD (HR=1.49 (95%CI=1.02-2.16), p=0.04). There was no difference in RI (HR=0.73 (95%CI=0.47-1.14), p=0.17), NRM (HR=1.25 (95%CI=0.78-2.02), p=0.36), LFS (HR=0.95 (95%CI=0.69-1.31), p=0.76), OS (HR=1.09 (95%CI=0.76-1.55), p=0.64) and GRFS (HR=1.07 (95%CI=0.81-1.42), p=0.64) between the groups. Presence of adverse cytogenetics was independently associated with higher RI (HR=1.90 (95%CI=1.20-2.99), p=0.006), inferior LFS (HR=1.59 (95%CI=1.15-2.19), p=0.005), inferior OS (HR=1.48 (95%CI=1.05-2.08), p=0.03), and worse GRFS (HR=1.54 (95%CI=1.17-2.04), p=0.002). Conclusion: Results show that patients undergoing haplo-transplantation with 4/8 (vs. 2-3/8) HLA mismatches have a higher incidence of chronic GVHD (all grades) without adversely affecting acute grade 2-4 GVHD, RI, LFS, OS and GRFS. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Blaise: Jazz Pharmaceuticals: Honoraria. McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Forcade: Novartis: Other: travel grant. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Mohty: Takeda: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Honoraria.

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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

A Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2746-2746 ◽  
Author(s):  
Eric D. Jacobsen ◽  
Ranjana H. Advani ◽  
Yasuhiro Oki ◽  
Jeff Sharman ◽  
Steven M. Horwitz ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Grey Zone ◽  
Advisory Committees

Abstract Abstract 2746 Background: Brentuximab vedotin (ADCETRIS®) is a CD30-directed antibody-drug conjugate approved for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Several non-Hodgkin lymphoma (NHL) subtypes such as diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphomas (PTCL) have variable quantitative and qualitative expression of CD30. As a result of the high objective response rate (86%) and durable complete remissions (CR) observed in a pivotal phase 2 study in ALCL, a study was initiated to investigate the efficacy and safety of brentuximab vedotin in other NHLs that express the CD30 antigen. Methods: A phase 2, open-label, single-arm, multicenter study is currently ongoing to evaluate the antitumor activity of brentuximab vedotin in approximately 75 patients with relapsed or refractory CD30-positive NHL (ClinicalTrials.gov NCT01421667). Brentuximab vedotin, 1.8 mg/kg, is administered every 3 weeks by IV infusion. Patients who achieve at least stable disease are eligible to receive continued treatment until disease progression or unacceptable toxicity. The primary efficacy endpoint is objective response rate (ORR) as assessed by the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Efficacy variables will be analyzed by total patients, WHO NHL classification, DLBCL (excluding peripheral mediastinal large B-cell lymphoma [PMBL] due to differing treatment paradigms and outcomes for this DLBCL subtype), and by each individual disease. The correlation between antitumor activity and quantitative CD30 expression is also being explored. Results: Fifty-three patients with various CD30-positive NHLs have been enrolled to date (35 with B-cell neoplasms and 18 with mature T-/NK-cell neoplasms). Twenty-nine (55%) patients had refractory disease, 19 (36%) had relapsed since their most recent prior therapy, and 5 (9%) had primary refractory disease (did not achieve a CR with frontline therapy or relapsed within 3 months of completing frontline therapy). Diagnoses include DLBCL (assorted disease subtypes, n=22), angioimmunoblastic T-cell lymphoma (AITL, n=9), PTCL-NOS (n=8), grey zone lymphoma (n=5), PMBL (n=4), follicular lymphoma (n=3), post-transplant lymphoproliferative disorder (n=1), and cutaneous T-cell lymphoma (n=1). The median age is 64 years (range 16–83) and 30 patients (57%) are male. Patients have received a median of 3 prior systemic therapies and 6 patients have received prior stem cell transplants. Of the 36 patients who have had a response assessment to date, 12 (33%) have achieved an objective response (5 CR, 7 partial remissions [PR]). The ORR for B-cell NHLs is 36% (9/25), and 27% (3/11) for mature T-/NK-cell NHLs. Thus far, responses are particularly noteworthy in DLBCL (excluding PMBL) where 7 of 15 patients (47%) have responded (3 CR, 4 PR), in AITL where 3 of 5 patients (60%) have responded (2 CR, 1 PR), and in grey zone lymphoma where 2 of 5 patients (40%) have achieved a PR. Median duration of response has not been reached. Of the 12 responding patients, 7 remain on treatment, 3 discontinued due to a patient decision (non-adverse event), and 2 due to adverse events of neutropenia (related) and pneumocystis jiroveci pneumonia (unrelated). CD30 expression levels for patients with a CR or PR were widely variable and ranged from <1% to 90%. Treatment-emergent adverse events (TEAEs) occurring in ≥10% of patients include fatigue (26%), diarrhea (16%), nausea (16%), pyrexia (16%), neutropenia (14%), dyspnea (12%), and abdominal pain (10%), and TEAEs considered related to study drug include fatigue (16%) and neutropenia (14%). Most AEs have been Grade 1 or 2. Grade 3 dyspnea, hyponatremia, and decreased white blood cell count have occurred in 2 patients each, while Grade 3 neutropenia has occurred in 3 patients. Two patients have experienced Grade 4 neutropenia. Peripheral neuropathy events have been Grade 1 or 2. Conclusions: In this interim analysis of 53 patients (36 with response evaluations), compelling antitumor activity has been demonstrated in both B-cell and mature T-/NK-cell NHLs, in particular DLBCL, AITL, and grey zone lymphoma. Due to the range of CD30 expression in patients achieving an objective response, more data are needed to determine if there is a correlation between CD30 expression and antitumor activity. Preliminary safety data are consistent with the safety profile of brentuximab vedotin. Disclosures: Jacobsen: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is indicated for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. These indications are based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with brentuximab vedotin. Advani:Seattle Genetics, Inc.: 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; Genentech: Research Funding; Pharmacyclics: Research Funding; Abbott: Research Funding. Oki:Seattle Genetics, Inc.: Research Funding. Sharman:Seattle Genetics, Inc.: Research Funding. Horwitz:Seattle Genetics, Inc.: Consultancy, Research Funding; Novartis: Consultancy; Millennium: Consultancy; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Allos Therapeutics: Consultancy, Research Funding; Merck: Honoraria; Genzyme: Research Funding; Infinity Pharmaceuticals: Research Funding. Forero-Torres:Seattle Geentics, Inc.: Research Funding, Speakers Bureau. O'Connor:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Shustov:Seattle Genetics, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Siddiqi:Seattle Genetics, Inc.: Consultancy, Research Funding. Grove:Seattle Genetics, Inc.: Employment, Equity Ownership. Bartlett:Seattle Genetics, Inc.: Consultancy, Research Funding, Travel expenses Other.

Outcome and Prognostic Factors in Patients with Mantle Cell Lymphoma Relapsing After Autologous Stem Cell Transplantation: A Retrospective Study of the EBMT

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 474-474 ◽  
Author(s):  
Sascha Dietrich ◽  
Herve Finel ◽  
Ariane Boumendil ◽  
Irit Avivi ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Refractory Disease ◽  
Advisory Committees ◽  
Mantle Cell ◽  
One Year

Abstract Abstract 474 BACKGROUND: Autologous stem cell transplantation (autoSCT) is considered as standard treatment for non-frail patients with mantle cell lymphoma (MCL). However, little is known about outcome of MCL recurrence after autoSCT. We therefore conducted a retrospective analysis of patients with MCL who failed autoSCT using the EBMT database. PRIMARY OBJECTIVE was to analyse outcome and prognostic factors after relapse following autoSCT for MCL in the rituximab era. PRIMARY ENDPOINT was overall survival (OS) from relapse. ELIGIBLE were patients aged 18 years or more who relapsed following an autoSCT for MCL performed between 2000 and 2010 and who were registered with the EBMT. Centres were contacted to provide additional information on relapse treatment. STATISTICAL ANALYSIS was based on log-rank comparisons and multivariable testing using Cox regression models. RESULTS: 1054 patients meeting the eligibility criteria could be identified in the EBMT registry. Of these, a full data set could be retrieved for 382 patients. Sixteen patients had to be excluded due to loss of follow up (n=7), wrong diagnosis (n=6), or falsely reported relapse (n=3). Median age at autoSCT of 366 evaluable patients was 59 years (range: 37 to 76), 290 patients (79%) were men. 64% had undergone autoSCT as part of 1st-line therapy; 68% and 49% had documented exposure to rituximab (RTX) and high-dose ara-C (HA) before autoSCT; and 12% had had refractory disease at autoSCT. Median time from autoSCT to relapse was 20 months (range: 0.4 to 117). 21 relapses (6%) occurred beyond 5 years after autoSCT. With a median observation time of 37 months (95% CI 32–43), median OS after relapse of the whole study group was 20 months. By univariate analysis, a long (>12mo) interval between autoSCT and relapse (p<0.001; HR 0.26; Figure 1A), 1st-line autoSCT (p=0.006; HR 0.7) refractory disease at autoSCT (p<0.001, HR 2.0) and more recent year of relapse (p<0.001, HR per year 0.9) significantly influenced OS from relapse, whereas age, gender, RTX and HA exposure did not. By multivariate analysis refractory disease at autoSCT (p<0.001, HR=2.14), remission duration after autoSCT (p<0.001 HR per 3 months 0.88) and calendar year of relapse (p<0.03, HR per year 0.93) were confirmed to be predictors for OS. In addition, HA exposure prior autoSCT adversely affected OS from relapse (p=0.06, HR 1.38). Salvage chemotherapy after relapse resulted in only 31% complete responses and 29% partial responses, whereas 40% of patients have been refractory to first salvage chemotherapy. 83 patients (23%) received an allogeneic SCT (alloSCT), whereas only 7 patients (2%) received a second autoSCT after relapse. Median time after relapse to second SCT was 7 months (range: 1 to 40). Survival after relapse for patients who received a second autoSCT was poor with no long-term survivor. AlloSCT performed for late relapse (>12mo) after autoSCT was associated with superior OS compared to patients who received an allograft upon a shorter remission duration after autoSCT (5-year OS from alloSCT 50% vs 0%; p=0.001; Figure 1B). Achievement of CR before alloSCT (p=0.05 HR=0.5), but not donor source, T-cell depletion or conditioning intensity affected OS after alloSCT. CONCLUSIONS: Patients with MCL who relapse within one year after autoSCT have an extremely dismal outcome even with alloSCT. In contrast, about half of the patients who have MCL recurrence beyond one year after autoSCT and can undergo salvage alloSCT enjoy long-term survival. It remains to be shown if a similarly good outcome can be achieved without alloSCT in this favourable selection of patients. A 2nd autoSCT does not appear to be a promising option in patients with MCL failing a 1st autoSCT. Disclosures: Walewski: Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Cephalon: Research Funding.

Sequence Impact Of Pomalidomide and Carfilzomib On Treatment Response In Relapsed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1954-1954 ◽  
Author(s):  
Tomer M Mark ◽  
John N. Allan ◽  
Angelique Boyer ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Board Of Directors ◽  
Research Funding ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Advisory Committees ◽  
Effective Response ◽  
Disease Response ◽  
Prior Therapy

Abstract Background Pomalidomide and Carfilzomib (Cfz) are two recently approved agents for the treatment of multiple myeloma (MM) that has relapsed after prior therapy including an IMiD and bortezomib. The sequencing of these agents to achieve maximum tumor reduction is thus far not known. We have previously reported response data from the combination clarithromycin, pomalidomide, dexamethasone (ClaPD) for relapsed or refractory MM. (Mark et al, ASH 2012). We examined the subset of these patients that had received a Cfz-based regimen prior to ClaPD as well as the subset of patients that received a Cfz-based regimen after ClaPD to determine whether the sequence of agents had any impact on response. Methods One hundred nineteen patients with heavily pretreated RRMM were enrolled into a single-institution study to investigate the effectiveness and tolerability of ClaPD. Eligible subjects had at least 3 prior lines of therapy, one line of which must have included lenalidomide. ClaPD is clarithromycin 500mg twice daily; pomalidomide 4mg for days 1-21, and dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle. Two subsets of patients were compared: 1) Subjects that had received treatment with a Cfz-based prior to ClaPD (CP) and 2) Subjects that had received a Cfz-based therapy after progression on ClaPD (PC). Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Results Fourteen patients comprised CP and 20 in PC. Patients in the CP group were more heavily pre-treated with a median of 6 (range 3-15) lines of therapy, as compared to 5 lines (range 3-10) for PC. Responses are shown in Table 1. Median cycles of ClaPD and Cfz received in PC was 6.5 (range 2-16) and 5 (1-14), respectively. Median cycles of Cfz and ClaPD in the CP group was 8 (1-19) and 5 (1-23), respectively. CR complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate Conclusions ClaPD and a Cfz-based regimen appear to have equally effective response regardless of sequence in salvage chemotherapy. Somewhat deeper responses are seen with ClaPD after Cfz as compared to Cfz after ClaPD, which is intriguing given that the CP group had more prior lines of treatment than PC. Longer follow-up to analyze duration of the response is needed prior to concluding which sequence (PC vs CP) is more effective. This data supports the use of pomalidomide after carfilzomib failure and vice-versa as potent salvage therapeutic options. Disclosures: Mark: Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Zafar:Celgene: Speakers Bureau; Millennium: Speakers Bureau; Onyx: Speakers Bureau. Pekle:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Niesvizky:Millennium: The Takeda Oncology Company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Incidence Of Hypotension In Patients With Multiple Myeloma During High Dose Chemotherapy and Autologous Stem Cell Rescue

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3324-3324 ◽  
Author(s):  
Priya Sehgal ◽  
Noa Biran ◽  
Gagan Sahni ◽  
Ajai Chari
Keyword(s):  
Board Of Directors ◽  
Discharge Summary ◽  
Infectious Complications ◽  
High Dose ◽  
Inclusion Criteria ◽  
Advisory Committees ◽  
Gastrointestinal Complications ◽  
Group 2 ◽  
Al Amyloid ◽  
Group 1

Abstract Background The median age of patients diagnosed with multiple myeloma (MM) is 69. Up to 60-80% of patients in this age group have hypertension (HTN) (Burt VL et al. Hypertension 1999), and are on anti-hypertensive medications. A standard treatment for MM is high dose melphalan (HDM) chemotherapy with autologous stem cell transplant (ASCT), which often results in gastrointestinal complications that can result in hypovolemia. The combined effect of anti-HTN agents and ASCT-related complications may result in blood pressure (BP) ranges that are precariously low. To date, the incidence of hypotension in the setting of ASCT for MM is unknown. In this case series of 102 patients who received ASCT for MM, we compare the characteristics of those who became hypotensive with those who did not. Methods We reviewed the charts of 102 consecutive MM/AL amyloid patients admitted for HDM chemotherapy with ASCT at Mount Sinai Hospital between May 2011 and June 2013. May 2011 was chosen as the date of inclusion because at this time, electronic medical records were implemented, allowing for detailed review of vital signs and other clinical data. Patients were classified into two groups. Patients included in group 1 demonstrated a drop in BP which was defined as meeting at least 1 of the following criteria: A) One or more anti-HTN medications were discontinued during ASCT B) Although normotensive on admission for ASCT, the median systolic or diastolic blood pressure (SBP or DBP) on date of discharge was ≤ 100 or 60 mm Hg respectively C) A decrease in SBP of ≥ 20 mm Hg was observed between admission and discharge Patients who did not meet any of the above criteria were classified into group 2. Baseline and peri- SCT characteristics of the two groups were compared using the chi square test. Results Of the 102 patients analyzed, 6 had AL amyloid and the remaining 96 had MM. 43 met at least one inclusion criteria for group 1 and the remaining 59 were classified as group 2. Specifically, of the patients in group 1, 18 met inclusion criteria A, 21 met inclusion criteria B, and 23 met inclusion criteria C. Among the patients in group 1 who met 2 criteria: 4 patients met criteria A and B, 4 patients met criteria A and C, and 9 patients met criteria B and C. Baseline characteristics including median age (64 and 63), gender distribution (55.8% and 47.5% females respectively), and a history of HTN (41.9% vs. 37.3%) were comparable in both groups (p>0.05). The median length of stay was 17 days in both groups. The incidence of gastrointestinal complications was comparable in both groups including diarrhea 72.1% vs. 62.7%, mucositis 14.0 % vs 8. 5%, and Clostridium difficile infection 9.3% vs. 6.8%. The ensuing weight loss in the 2 groups was also comparable 2.4 kg and 1.9 kg respectively. The incidence of infectious complications was similarly comparable in the 2 groups with fever 51.1 % vs 61% and bacteremia occurring in 7.0% vs 11.9%. Of the 43 patients in group 1, one patient had shock requiring ICU transfer for vasopressors in the setting of adrenal insufficiency and sepsis/bacteremia. Interestingly, of the 102 included patients, only 15 were reported to have clinically significant hypotension on the discharge summary. Of these 15 patients, 3 experienced transient hypotension, (i.e. for 1 -2 days,) with rapid normalization of pressure, and therefore, did not meet our inclusion criteria of persistent hypotension. Conclusions Although the incidence of hypotension in this series of MM patients undergoing ASCT was 42%, only 15% had documentation of this occurrence in the discharge summary. Interestingly, there were no statistically significant differences in the risk factors for ASCT associated hypotension in the 2 groups, including gastrointestinal and infectious complications. Given the unexpectedly high incidence of hypotension during ASCT, consideration should be given to the following: 1) Prior to SCT, anti-HTN medications should not be added (as is sometimes done for perioperative clearance) or titrated up; 2) During ASCT, anti-HTN medications may need to be discontinued; 3) Prior to discharge from ASCT, physical therapy/orthostatic evaluation and risk of falls from new relative hypotension needs to be assessed, especially in the setting of recovering thrombocytopenia. Although further studies are required, we hypothesize that fatigue, presyncopal events, and falls post SCT could be minimized with increased attention to HTN management peri ASCT. Disclosures: Chari: Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Millenium : Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees.

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