scholarly journals Sequential Treatments in Chronic Phase Chronic Myeloid Leukemia (CML) Patients without Optimal Response after Frontline Nilotinib or Dasatinib: An Italian CML Campus Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-46
Author(s):  
Gabriele Gugliotta ◽  
Mario Annunziata ◽  
Isabella Capodanno ◽  
Davide Rapezzi ◽  
Immacolata Attolico ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Chronic Phase ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
Optimal Response ◽  
First Line Treatment

INTRODUCTION: Frontline therapy with second generation (2G) tyrosine-kinase inhibitors (TKIs) in chronic phase (CP) chronic myeloid leukemia (CML) patients demonstrated higher efficacy as compared to imatinib, with less patients experiencing treatment failure and progression to advanced disease. However, limited information are currently available on the management and outcome of those CML pts not achieving an optimal response to first-line treatment with a 2G-TKI. AIM: To describe the clinical outcome of CP CML patients without an optimal response to a frontline 2G-TKI that switched to alternative TKIs. METHODS: We performed a retrospective analysis in 22 Centers cooperating within the Italian CML Campus Project. Main inclusion criteria were: 1) diagnosis of CP-CML after 2010; 2) first-line treatment with a 2G-TKI; 3) switch to second-line treatment in case of non-optimal response (either following ELN recommendations or as for clinical practice); 4) CML in CP at the time of switching to second-line treatment. The main exclusion criteria were a switch to second-line treatment for intolerance or for low adherence to therapy. RESULTS: The main findings of this analysis are summarized in the table. Seventy-one pts meeting the inclusion/exclusion criteria were identified; the median age of pts at CML diagnosis was 46 (21-80) years. Sokal risk score was low, intermediate, and high in 24 (34%), 30 (42%), and 17 (24%) pts, respectively. First-line treatment was performed with nilotinib in 47 (66%) pts and dasatinib in 24 (34%) pts. According to the ELN 2020 recommendations, 51 (72%) pts fulfilled the criteria for "failure" and 20 (28%) pts those for "warning". BCR-ABL mutations were identified in 12 of 65 (18%) evaluable pts (T315I in 1 pt). Additional chromosomal abnormalities in Ph+ cells were identified in 6 of 54 (11%) evaluable pts. Second-line treatment was started after a median time of 16 (4-72) months, with ponatinib (40 pts, 56%), dasatinib (21 pts, 30%), nilotinib (7 pts, 10%), or bosutinib (3 pts, 4%). Median follow-up from start of second-line treatment was 25 (2-90) months. Best response to second-line treatment was MR2 in 18 (25%) pts and MR3 in 37 (51%) pts. Nineteen (27%) pts (13 for resistance and 6 for intolerance) switched to third-line treatment (ponatinib, 11 pts; nilotinib, 3 pts; dasatinib, 4 pts; imatinib, 1 pt), after a median time of 8 (1-72) months. Mutations were identified in 2 of 17 evaluable pts, and both patients harbored a T315I mutation. MR3 was reached by 9 (47%) of these pts. Lastly, 7 (10%) pts switched (6 for resistance and 1 for intolerance) to fourth-line treatment (asciminib, 4pts; dasatinib, 2 pts, nilotinib, 1 pt). Overall, 44 (62%) patients reached with sequential TKI treatments a MR3 (31/51 pts among "failures"; 13/20 among "warnings"). Allogeneic stem-cell transplantation (SCT) was performed in 7 (9.5%) pts (6 among "failures"), after a median time of 20 (15-60) months from CML diagnosis. Progression to advanced phase occurred in 2 (3%) pts; both pts previously met the ELN2020 "failure" criteria. Estimated 4-y PFS was 92.5%. Death occurred in 3 (4%) pts (1 after progression to blast phase, 2 for cardiovascular adverse events). Estimated 4-y OS was 93.7% CONCLUSION Our findings show that CP-CML patients not achieving an optimal response to frontline 2G-TKI therapy, despite a complex management, still have a favorable prognosis and survival due to the availability of both multiple TKI options and SCT. Figure Disclosures Gugliotta: Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Abruzzese:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Castagnetti:Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Di Raimondo:Amgen, Takeda, Novartis: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GILEAD, Incyte: Research Funding; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Rosti:Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Saglio:Pfizer: Research Funding; Ariad: Research Funding; Roche: Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding. Breccia:Abbvie: Consultancy; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

scholarly journals Management of Steroid-Refractory Graft-Versus-Host Disease - a Survey By the Transplant Complications Working Party of the EBMT

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2884-2884
Author(s):  
Zinaida Peric ◽  
Helene Schoemans ◽  
Christophe Peczynski ◽  
Christian Koenecke ◽  
Ivan S. Moiseev ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Working Party ◽  
Line Treatment ◽  
Second Line ◽  
Clinical Practices ◽  
First Line ◽  
Advisory Committees ◽  
Prospective Trials ◽  
First Line Treatment

Abstract Introduction: As there is limited evidence to guide management of patients with steroid-refractory graft-versus-host disease (SR-GVHD) there is a broad variability of clinical practices. To document the current practice and assess the impact of emerging new drugs in SR-GVHD, Transplant Complications Working Party (TCWP) of the EBMT performed a survey among EBMT centers that covered specific treatment decisions on first- and second-line treatment of acute and chronic GVHD (aGVHD and cGVHD). Methods: The survey was conducted from December 2020 to March 2021 among EBMT centers. A questionnaire was developed by the study authors and used for data collection. It consisted of 40 questions focused on general approach in the first-line treatment, preferred second-line treatment in SR-GVHD and ancillary care in aGVHD and cGVHD. Results: 145 centers from 33 countries agreed to participate and responded to the questionnaire. First-line treatment of aGVHD was reported as rather homogenous; with most centers (68%) starting with lower doses of corticosteroids (CS) (<2mg/kg) in lower grade aGVHD (grade 2a) and most centers (88%) starting with higher doses (2mg/kg) in aGVHD grades >2b. On the other hand, the evaluation of response to CS was more heterogeneous: at 3 days in 33%, at 5 days in 30%, at 7 days in 15% of centers and depending on severity of aGVHD in most other centers. In the presence of SR-aGVHD, 50% of centers consider inclusion of patients in clinical trials. Although as much as 85% of centers reported to have a standard operating procedure (SOP) for SR-aGVHD management, only 45% (n=66) have an established one or 2-agent second-line treatment; most frequently ruxolitinib (n=46) and/or extracorporeal photopheresis (ECP) (n=29). All other centers reported a very heterogeneous practice and listed multiple agents (range, 3-10) as second-line treatment options. In total, the most used agents for SR-aGVHD as shown in Figure 1A are ruxolitinib in 68%, ECP in 59%, mycophenolate-mofetil (MMF) in 27%, calcineurin inhibitors (CNI) in 25%, high-dose CS (>2mg/kg) in 15%, mesenchymal stem cells (MSC) in 14%, etanercept in 13%, infliximab in 11% and anti-thymocyte globulin (ATG) in 10% of centers. Clinical practice in first-line treatment of cGVHD again appeared relatively homogeneous; 58% of centers reported to treat mild forms with topical treatment only, unless affected organs could not be reached topically. In moderate/severe cGVHD, the majority (71%) of centers start with 0.5-1mg/kg of CS, in 45% with addition of CNI, while others use higher doses of CS +/- other agents. The evaluation of response was done before 4 weeks in 41% of centers, between 5-8 weeks in 41%, while a minority performed later response assessment or based the latter on organ affection/severity. In case of SR-cGVHD, 56% of centers would consider the inclusion in clinical trials, while only 65% have a SOP on management of these patients. One third of centers (35%) has an established multidisciplinary cGVHD team. Practices for SR-cGVHD again varied significantly, with most centers reporting on the use of more than 2 agents (range, 3-13) as second-line and with most applied agents as depicted in Figure 1B; ruxolitinib and ECP in 68% of centers, CNI in 40%, MMF in 37%, rituximab in 27%, imatinib in 25%, mTOR inhibitors in 23%, ibrutinib and methotrexate (MTX) in 19%, pulse of CS in 17%, MSC in 12% and PUVA therapy in 10% of centers. Conclusions:In summary, this survey revealed a rather homogenous first-line management of aGVHD and cGVHD based on steroids in the majority of centers. However, when first-line fails, the definition of SR-GVHD remains highly variable and SR-GVHD is still treated with a seemingly "trial and error" approach as demonstrated by significant variability of clinical practices among EBMT centers for second-line treatment. However, in line with recently published prospective trials, ruxolitinib comes forth as one of the most used therapeutic modalities in both SR-aGVHD and cGVHD, together with already widely administered ECP. On the contrary, ibrutinib has not emerged as standard of care in this setting. Future efforts should be invested in finding a standardized approach in SR-GVHD by directly comparing most applied second-line agents in prospective trials as well as evidence-based personalized treatment approaches. Figure 1 Figure 1. Disclosures Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Schoemans: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: personal fees , Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants and personal fees; Gilead: Other: travel grants; CIBMTR: Consultancy, Other: travel grants; Janssen: Membership on an entity's Board of Directors or advisory committees; BHS: Membership on an entity's Board of Directors or advisory committees, Other: travel grants and personal fees , Research Funding; Jazz Pharmaceuticals: Other: personal fees; Takeda: Other: personal fees. Koenecke: Novartis: Consultancy; Janssen: Consultancy; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; EUSA Pharm: Consultancy. Basak: Saventic Health: Current holder of individual stocks in a privately-held company. Greinix: Celgene: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Therakos: Consultancy. Penack: Omeros: Consultancy; Shionogi: Consultancy; Priothera: Consultancy; Incyte: Research Funding; Takeda: Research Funding; Therakos: Honoraria; Pfizer: Honoraria; Neovii: Honoraria; Novartis: Honoraria; MSD: Honoraria; Jazz: Honoraria; Gilead: Honoraria; Astellas: Honoraria.

scholarly journals Predictors of Glucocorticoid Responsiveness in Multicentric Castleman's Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Kazutoshi Ebisawa ◽  
Arika Nukina Shimura ◽  
Akira Honda ◽  
Yosuke Masamoto ◽  
Fumio Nakahara ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Castleman’S Disease ◽  
Line Treatment ◽  
Second Line ◽  
Castleman's Disease ◽  
First Line ◽  
Advisory Committees ◽  
First Line Treatment

Background: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disease accompanying various symptoms and multi-organ dysfunctions. Although anti-interleukin-6 monoclonal antibodies, tocilizumab and siltuximab are recommended as a therapeutic option, these treatments require patients to visit hospitals at least once a month for many years, and the drug costs are quite high. In Japan, where tocilizumab is the only biological agent covered by the medical insurance, glucocorticoid monotherapy is still an important treatment option. In fact, a part of MCD patients initially treated with glucocorticoids could be successfully controlled without adding or switching to other agents. Considering that emergence of neutralizing anti-drug antibodies which reduced therapeutic efficacy could also be a clinical problem in MCD, there would be a rationale for reserving newer agents for future relapse by using glucocorticoids as first-line treatment for potential responders. Here, we retrospectively analyzed clinical characteristics of MCD patients treated in our institution to explore factors predicting who could be successfully treated with glucocorticoid monotherapy. Methods: We retrospectively reviewed histologically confirmed Castleman's disease patients who visited the Department of Hematology and Oncology of the University of Tokyo Hospital from January 2000 to March 2020. Based on the diagnostic criteria of Castleman Disease Collaborative Network (CDCN), MCD was diagnosed when enlarged lymph nodes were present in more than 2 lymph node stations and laboratory and/or clinical diagnostic criteria were met. Unicentric Castleman's disease (UCD) was diagnosed when only one single lymph node region was involved. MCD patients who were initially treated with prednisolone (PSL) were divided into two groups: patients who continued PSL until the latest follow-up (PSL-only group) and patients who received subsequent treatment (Second-line group). Results: 8 patients with UCD and 27 patients with MCD were included in our analysis. With a median follow-up of 5.2 years, 21 MCD patients underwent first-line treatment (PSL, n=18; tocilizumab, n=3). Compared to patients who did not receive any treatment, patients who underwent treatment had marginally higher levels of CRP (7.15 mg/dl vs 4.17 mg/dl, respectively; p=0.066) and significantly lower levels of hemoglobin (9.5 g/dl vs 12.5 g/dl, respectively; p=0.036). Seven out of 18 patients initially treated with PSL had received subsequent treatments (tocilizumab, n=6; rituximab, n=1). Among the PSL-only group, biochemical responses at the latest follow-up could be assessed for 10 in 11 patients: two in complete response, five in partial response, two in stable disease, and one in progressive disease, based on the response criteria of CDCN. Compared to PSL-only group, patients classified into second-line group had higher levels of CRP (11.88 mg/dl vs 6.24 mg/dl, respectively; p=0.024) and lower hemoglobin levels (6.4 g/dl vs9.4 g/dl, respectively; p=0.033). Patients whose CRP levels were lower than 12 mg/dl before starting PSL had significantly longer time to next treatment (TTNT) (median not reached vs 0.88 years; HR, 0.078 [95%CI: 0.013-0.48], p=0.00044). Similarly, patients whose hemoglobin levels were more than 8 g/dl had marginally longer TTNT (median not reached vs 2.63 years; HR, 0.22 [95%CI: 0.040-1.17], p=0.054). In addition, patients with either Hb < 8 g/dl or CRP ≧12 mg/dl had significantly shorter TTNT (median not reached vs 2.12 years; HR, 0.090 [95%CI: 0.010-0.77], p=0.0074). The median PSL dose at the latest follow-up in PSL-only group was 3 mg per day [interquartile range: 0-5 mg per day], which would be comparably safe considering previous reports indicating that PSL dose of less than 5 mg per day was associated with lower incidence of adverse events. Conclusion: Out data suggest that glucocorticoid monotherapy has a good potential to induce sustained disease control for MCD patients with higher Hb or lower CRP levels. Furthermore, PSL doses could be tapered to safer doses among patients who could continue PSL until the latest follow-up. In contrast, the efficacy of glucocorticoids for MCD patients with lower Hb or higher CRP levels were limited. Such patients would be good candidates for novel agents such as tocilizumab or rituximab. Disclosures Honda: Nippon Shinyaku Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau. Nakahara:Eisai Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Bristol-Myers Squibb Company: Honoraria. Kurokawa:Chugai: Consultancy, Research Funding, Speakers Bureau; Sanwa-Kagaku: Consultancy; Pfizer: Research Funding; Otsuka: Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Teijin: Research Funding; Eisai: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; Nippon Shinyaku: Research Funding, Speakers Bureau; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Bioverativ Japan: Consultancy; Shire Plc: Speakers Bureau; Jansen Pharmaceutical: Speakers Bureau; Ono: Research Funding, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; MSD: Consultancy, Research Funding, Speakers Bureau.

scholarly journals Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4112-4112
Author(s):  
Charline Moulin ◽  
Romain Morizot ◽  
Thomas Remen ◽  
Hélène Augé ◽  
Florian Bouclet ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Long Term Survivors ◽  
First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Major Improvement of Invasive Aspergillosis Outcome Is Not Enough to Improve Overall Survival In Allogeneic Hematopoietic Stem Cell Transplant Recipients: Results From a Single-Center Retrospective Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1244-1244
Author(s):  
Géraldine Salmeron ◽  
Raphaël Porcher ◽  
Anne Bergeron ◽  
Marie Robin ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
First Line Treatment

Abstract Abstract 1244 Background. Voriconazole (V) treatment has been shown to improve the 12 week (W) survival rate of hematological patients (pts) with invasive aspergillosis (IA), including recipients of allogeneic hematopoietic stem cell transplants (HSCT). We investigated whether this early survival advantage could translate into a significant increase in overall survival. Methods. We retrospectively reviewed all consecutive pts who received a transplant between Sept. 1997 and Dec. 2008 at Saint-Louis Hospital and were diagnosed as having IA. The temporal origin of the study was the date of IA diagnosis for each patient. Factors associated with survival were analyzed using Cox proportional hazard models. Separate models were estimated for survival up to 12 W and for survival between 12 W and 24 months (M) in pts surviving longer than 12 W. The deaths of pts with and without IA were analyzed with a competing risk framework. Cumulative incidence curves were compared using Gray's tests. Results. Our study examined 89 IA pts. The median follow-up was 70 M (range, 11–130 M). Two pts did not receive any antifungal treatment and were excluded from subsequent analyses. Of the 87 pts, 42 received first-line V and 45 primarily received a lipid formulation of amphotericin B (n=25), amphotericin B deoxycholate (n=10), caspofungin (n=8) or itraconazole (n=2). The primary characteristics of pts with IA and their causes of death, separated by V as first-line treatment, are shown in the table below. The median survival was 2.6 M, and the overall survival at 24 M was 19% (95% CI 12–30 M) (see figure). Overall, the survival rates of the two groups were significantly different (P= 0.010). However, the differences in survival were quite dramatic prior to 10 M, whereas both survival curves became very close after one year. At 18 M, the numbers of surviving pts were almost identical in the two groups [19% (95% CI: 11–34%) in pts who did not receive V as first-line treatment vs. 21% (95% CI 11–38%) in pts who did]. Pts who did not receive V as a first-line treatment displayed a higher probability of dying from IA than those who did (P=0.004), whereas opposite results were found for mortality in pts without IA (P=0.006). The 24-M cumulative incidence of death from IA was 47% (95% CI 31–61%) in the no V group and 19% (95% CI 9–33%) in the group treated with V. The 24-M cumulative incidence of death in pts without IA was 4% (95% CI 7–14%) in the no V group and 27% (95% CI 14–42%) in pts treated with V. The probability of death from another cause, with IA, was similar in both groups (29% vs. 36% at 24 M; P=0.46). After adjusting for donor type, conditioning regimen, progressive GVHD at diagnosis of IA and cumulated steroid dose (mg/kg) in the W preceding IA diagnosis, administration of V as first-line treatment was found to decrease the risk of death during the first 12 W by approximately 70% [HR=0.31 (95% CI 0.16–0.60); P=0.0005]. Conversely, analysis of mortality between 12 W and 24 M failed to identify any significant predictor of risk of death; however, only 24 pts died during this period. Conclusions. The finding that first-line treatment with V, which is associated with a tremendous improvement in IA outcome, does not translate into an increase in overall survival (even in the context of early diagnosis) is striking. Diagnosis of IA following HSCT, whatever the outcome, appears to be a strong marker for poor long-term prognosis. Disclosures: Bergeron: Pfizer: Speakers Bureau, none; Merck: Speakers Bureau, none; Schering: Speakers Bureau, none. Sulahian:Pfizer: Research Funding, non; Merck: Research Funding, none. Ribaud:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, none; Schering: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, none; Gilead: Speakers Bureau, none.

Clinicopathological Features of Nodular Sclerosis-Type Classical Hodgkin Lymphoma In the Elderly: Multicenter Study of Hodgkin Lymphoma In Japan

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2677-2677
Author(s):  
Naoko Asano ◽  
Tomohiro Kinoshita ◽  
Koichi Ohshima ◽  
Tadashi Yoshino ◽  
Nozomi Niitsu ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
The Elderly ◽  
Clinicopathological Features ◽  
Line Treatment ◽  
Classical Hodgkin Lymphoma ◽  
First Line ◽  
Advisory Committees ◽  
First Line Treatment

Abstract Abstract 2677 Background: Classical Hodgkin lymphoma (CHL), which is characterized by the presence of Hodgkin and Reed Sternberg (H-RS) cells in a background of non-neoplastic inflammatory cells, is divided into four histological subgroups, nodular sclerosis (NSCHL), mixed cellularity (MCCHL), lymphocyte-rich, and lymphocyte depletion. While NSCHL in young adults is characterized by a mediastinal mass and good prognosis, the clinicopathological characteristics of NSCHL in the elderly (NSCHL-e) remain uncertain. Patients and methods: Enrolled patients were diagnosed with CHL between 1986 and 2006 as part of the Hodgkin Lymphoma's Multicenter Study Group. To better characterize NSCHL-e, we compared the clinicopathological profiles of 84 NSCHL-e patients aged 50 or over with 237 NSCHL-y patients aged 49 or younger and 302 with MCCHL. Results: The total of 743 CHL patients consisted of 496 men and 247 women with a median age of 48 years (range, 15– 89 years). The pathological diagnoses were NSCHL in 324 patients (43%) and MCCHL in 303 (41%). NSCHL patients showed a bimodal age distribution, with an initial peak in their 20s and a second small peak in their 60s. We categorized the former as NSCHL-y (49 or younger) and the latter as NSCHL-e (50 and over). NSCHL-e patients were characterized by male predominance and a more advanced clinical stage (53%) than NSCHL-y. Immunophenotypically, H-RS cells had the prototypic immunophenotype of CD15+ CD30+ and Pax5+. NSCHL-e cases showed a significantly higher rate of CD20 (24%) than NSCHL-y (8%, P = 0.001). Furthermore, H-RS cells in 29 of 75 (39%) patients with NSCHL-e were positive for EBV RNA transcripts by in situ hybridization, whereas only 7% of NSCHL-y cases were EBER-positive (P < 0.0001) (Table). Regarding NSCHL-e and MCCHL, no significant difference between these patients was seen in clinical characteristics. Immunophenotypically, NSCHL-e patients showed significantly higher rates for CD3 and TIA-1, while MCCHL patients showed higher EBV positivity (75%). Fifty-five of 63 patients received systemic multi-agent chemotherapy as first-line treatment, consisting of doxorubicin, bleomycin, vinblastine, and dacarbacin (ABVD) in 38 patients; CHOP in 8; C-MOPP in 8; and BEACOPP in 1. Overall, 51 patients responded to first-line treatment, 39 with complete response and 12 with partial response. Disease-specific survival of NSCHL-e was poorer than that of NSCHL-y (P < 0.001) but similar to that of MCCHL (P = 0.43) (Figure). Conclusion: NSCHL-e is characterized by an unfavorable prognosis and different clinicopathological features to NSCHL-y, which is considered as typical NSCHL. A number of cases of NSCHL-e might have been associated with MCCHL, with most being EBV-positive. These results suggest the limitations of current histological subgroupings for CHL. Disclosures: Matsushita: Pfizer CO.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Co.: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Predictors of Early Relapse Following Initial Therapy for Systemic Immunoglobulin Light Chain Amyloidosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2082-2082
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Initial Therapy ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Early Relapse ◽  
First Line Treatment

Abstract Introduction Immunoglobulin light chain amyloidosis (AL Amyloidosis) is a monoclonal plasma cell proliferative disorder that is characterized by tissue deposits of misfolded insoluble κ or λ light chain derived amyloid fibrils, leading to organ dysfunction. The prognosis of patients depends on the number and severity of organ involvement, especially cardiac involvement. Autologous stem cell transplant (ASCT), if eligible, alkylator (melphalan) and novel drugs like proteasome inhibitors (PI) and immunomodulators (IMiD) have improved the overall survival (OS) during the past decades. But still, nearly half of the patients die within a year of diagnosis. We analyzed the factors predicting early relapse / progression or death (within 12 months) after first line therapy for systemic AL amyloidosis. Methods Clinical and laboratory data of all consecutive patients with systemic AL amyloidosis seen at Mayo Clinic within 90 days of their diagnosis, between 2006 and 2015, was collected by chart review and analyzed retrospectively. Patients who died within 3 months of starting the first line treatment were excluded from analysis. Early relapse (ER) was defined as relapse / progression requiring treatment change / re-institution or death within 12 months of starting first line treatment. Patients in the cohort with ER were compared with patients with a follow up of more than 12 months who had a relapse / progression beyond 12 months or had continuing response at the time of analysis. Categorical variables were analyzed using chi - square and Fisher's exact test and continuous variables using Kruskal- Wallis test and Wilcoxon rank sum test. Multivariate analysis was done using logistic regression model. Results Seven hundred and eighty six patients with newly diagnosed systemic AL amyloidosis met the study criteria and were included in the analysis. Among these, 230 (29.3%) patients had ER within 12 months of starting initial therapy while 556 (70.7%) patients either relapsed after 1 year or had continuing response at the time of analysis. Baseline demographics, organ involvement and type of first line therapy are presented in Table1. The median estimated follow up for the entire cohort from start of initial therapy was 62.9 months (95% CI; 59.9, 67.3). The variables included in the univariate and multivariate analyses for factors predicting ER were age at diagnosis (≤ vs > 70 years ), revised mayo stage (I and II vs III and IV), bone marrow plasma cell percentage (BMPC; ≤ 10% vs > 10%), presence of any chromosomal abnormalities, trisomies or IgH translocations by fluorescence in situ hybridization (FISH), multiorgan involvement [(>1 vs 1) (heart, liver, kidney, gastrointestinal tract, autonomic neuropathy), incorporation of ASCT in initial therapy. In univariate analysis, mayo stage (p<0.0001), multiorgan involvement (p=0.0008) and inclusion of ASCT as part of initial therapy (p<0.0001) were significantly associated with ER, while age (p=0.06), BMPC(p=0.9), FISH abnormalities (p=0.2) were not. However, in multivariate analysis, only mayo stage (III + IV vs I + II; p=0.01) and non-inclusion of ASCT in first line treatment (p=0.0001) were significantly predictive of ER. Conclusions Despite the introduction of ASCT and novel drugs, the early mortality in systemic AL amyloidosis remains high. This study demonstrates that patients with ER are older with higher prevalence of cardiac involvement and multiorgan involvement and higher Mayo stage (III and IV). Incorporation of ASCT as part of the initial therapy was associated with reduced early relapse, but it is difficult to separate the influence of the eligibility for ASCT from the effect of ASCT itself. This will help us in characterizing these patients to better understand their mechanisms of resistance to therapy and gives an insight to the type of initial therapy that benefits them. Disclosures Dispenzieri: GSK: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Research Funding; pfizer: Research Funding. Kapoor:Takeda: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Kesios: Consultancy; BMS: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Glycomimetics: Consultancy; Millennium: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; AbbVie: Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding.

scholarly journals Potentially Cured Follicular Lymphoma (PC-FL). an Analysis of 56 Cases with Prognostic Factors Evaluation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5328-5328
Author(s):  
Samantha Ferrari ◽  
Alessandra Tucci ◽  
Gloria Valimberti ◽  
Antonella Anastasia ◽  
Chiara Bottelli ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Median Duration ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
Younger Age ◽  
First Line Treatment

Abstract Introduction: Advanced stage follicular lymphoma (FL) is generally considered incurable. Although multiple remissions after treatment are possible, relapse is considered the rule, and the time to progression tends to become shorter after each relapse (Johnson, JCO 1995). Over the last decades, after the introduction of monoclonal anti-CD20 antibodies and of better treatment programs, the prognosis of FL has markedly improved from a median OS of 7 years to a 10-year OS rate >80%. Moreover, clinical observations of patients (pts) experiencing very long progression-free periods despite more than one previous treatment failure, have become not rare, suggesting that some pts could achieve operational FL cure. To assess the frequency of those prolonged long-term remissions and search for potential predictive factors, we have retrospectively analyzed the consecutive series of pts with FL seen at our institution. Methods: FL pts, aged >18 years, in maintained remission for more than 5 years after at least two lines of treatment were selected as "potentially cured" FL (PC-FL) and analyzed in detail. Their main characteristics at diagnosis and at last relapse, the different lines of treatment received and the time intervals (time to next treatment: TTNT) between them, were recorded and compared with those of FL pts seen in the same period (control group). Treatment strategies used were grouped and defined as follows: radiotherapy or surgery, for stage I-II (local), anthracycline and/or alkylating agents regimens (Alk/Ant), purine analogues regimens (Pur), monoclonal antibodies/radioimmunoconjugates as single agent (MoAb), autologous transplantation (ASCT). Results and discussion: Among 385 consecutive FL pts seen from January 1987 to December 2011, 56 (14,5%) met criteria for PC-FL. Their clinicopathological features at diagnosis, compared to controls, are shown in Table I. There were no significant differences except for a younger age (51 vs 58 years, p<0.00016) and for a lower frequency of grade 3a histology (p=0.04) in PC-FL pts. First line treatment used did also not differ (p=0.29). Among PC-FL pts, 33 received two, 16 received 3 and 7 more than 3 treatment lines. The median duration of last complete remission was 118+ months, whereas the median duration of the remission preceding the last treatment had been 24 months; disease duration from diagnosis to the last relapse preceding long term remission had been 50,5 months. The last treatments received before long-term remission were variable including local in 10 (18%), Alk/Ant in 5 (9%), Pur in 11 (19%), MoAb in 10 (18%) and ASCT in 20 (36%). Pts characteristics at last relapse and remission duration were similar among different treatment subgroups, except that more pts in localized stage received local treatments. Comparing clinicopathological characteristics of PC-FL pts at diagnosis and at last relapse there were no differences except for FLIPI score, which was significantly lower at relapse (low FLIPI 34% at diagnosis, 68% at relapse, p=0.002). First-line and last treatments were similar except that more pts underwent ASCT as last treatment, as expected since frontline ASCT is not recommended. In 10 pts TTNT after first-line was longer than 5 years and 7 of them are still in prolonged remission (median 11+ years) after second-line treatment, representing a particularly favorable subgroup. In 26 (46%) of PC-FL pts TTNT was shorter than 24 months after first line therapy. Among 14 of them who received R-chemo at diagnosis (POD24, Casulo, JCO 2015), 8 (57%) obtained long remission after ASCT, given in second line in six. Conversely, ASCT was used in only 1 of 12 pts not receiving Rituximab at diagnosis. Conclusions: Approximately 15% of FL pts could currently achieve a very prolonged remission of about 10 years, even after multiple relapses. Its duration was 5x that of the last treatment line and more than twice that of active lymphoma, strongly suggesting the possibility of having achieved lymphoma cure. Younger age and grade 1-2 FL histology at diagnosis, and FLIPI low risk at relapse favored the achievement of PC-FL status. No specific treatment was associated with PC-FL and even an early relapse after first line treatment did not preclude to reach PC-FL, although early ASCT may be more effective for POD24 patients. Whether the achievement of PC-FL status may be related to biological factors will be interesting to be investigated in the next future. Disclosures Rossi: Roche: 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; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria.

An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 902-902 ◽  
Author(s):  
Ian W. Flinn ◽  
Richard H. Van der Jagt ◽  
Brad S. Kahl ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Board Of Directors ◽  
Research Funding ◽  
Standard Treatment ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Pharmaceutical Industries ◽  
Grade 3 ◽  
First Line Treatment

Abstract Abstract 902 Background Bendamustine (B) is an active agent for relapsed and refractory indolent NHL, both as monotherapy and combined with rituximab (R), results recently updated by the StiL study group. This study compared efficacy and safety of BR with standard treatment regimens of R-CHOP and R-CVP as first-line treatment for indolent NHL or MCL. Methods Patients were randomized to 6–8 cycles of BR or R-CHOP/R-CVP (R-CHOP or R-CVP determined by investigator prior to randomization). BR regimen was B 90 mg/m2/day on days 1 and 2 plus R 375 mg/m2on day 1 of a 28-day cycle. Standard dosing and 21 day cycles were used for R-CHOP and R-CVP. Primary objective was to demonstrate noninferiority of complete response (CR) rate of BR vs standard treatment (noninferiority margin [ratio] 0.88). Secondary measures included overall response rate (ORR), progression-free survival, and overall survival. Tumor response was determined by a blinded independent review committee (IRC) using International Working Group revised response criteria for malignant lymphoma. Investigator assessments were compared with those of the IRC. Results Of 447 randomized patients, 436 received treatment (BR n=221; R-CHOP/R-CVP n=215 [R-CHOP n=99; R-CVP n=116]) and were evaluable for safety. Of these, 419 patients (BR n=213; R-CHOP/R-CVP n=206 [R-CHOP 97; R-CVP n=109]) were evaluable for efficacy. The randomized groups were well matched for age (median 60 and 58 years), sex (male, 61% and 59%), ECOG status (64% performance status 0, both groups), lymphoma type (83% indolent NHL, both groups), and Ann Arbor stage (62% stage IV, both groups). Among randomized patients and efficacy evaluable patients, the IRC-assessed CR rate was numerically higher for BR than R-CHOP/R-CVP and statistically noninferior (Table). In the randomized groups, CR rates for indolent NHL were numerically similar between BR and R-CHOP/R-CVP; however, in MCL, BR was statistically superior (P=0.018) (Table). Investigator-assessed response in randomized patients found superiority of BR vs R-CHOP/R-CVP (P=0.0013). IRC and investigator assessments differed mainly in quality of response (CR vs partial) rather than in whether a patient was a responder. For randomized patients, the ORR was 94% for BR and 84% for R-CHOP/R-CVP. Time-to-event data are immature and will be analyzed later. At time of data cut-off, 8% of the BR group had progressed, relapsed, or died, compared with 4% of R-CHOP/R-CVP group. Most patients completed 6 cycles (92% for BR and 91% for R-CHOP/R-CVP), with high relative dose intensity (>96%). Dose delays were more common for BR-treated patients (35% vs 19%), and dose reductions were less common (22% vs 29%). Most common AEs for BR and R-CHOP/R-CVP, respectively, were nausea (139 vs 102 patients), fatigue (113 vs 107), neutropenia (76 vs 85), constipation (65 vs 90), and alopecia (8 vs 74). Laboratory grade 3/4 hematologic toxicities for BR and R-CHOP/R-CVP were lymphopenia (137 vs 64), neutropenia (98 vs 151), leukopenia (84 vs 116), thrombocytopenia (16 vs 15), and anemia (6 vs 9), respectively. The most frequent investigator-reported nonhematologic grade 3/4 AEs for BR and R-CHOP/R-CVP were infusion-related reaction (13 vs 8 patients). Granulocyte colony stimulating factors were given at investigator discretion (per ASCO recommendations) to 29% of the BR group and 43% of the R-CHOP/R-CVP group. Fatal AEs occurred in 6 BR patients (pneumonia, respiratory failure, and sepsis; acute respiratory failure; cardiac arrest; pneumonia; chronic obstructive pulmonary disease; lung cancer) and 1 R-CHOP/R-CVP patient (sepsis). Conclusion In patients with advanced indolent NHL and MCL, BR produces a CR rate that is noninferior to that of R-CHOP/R-CVP. In the subgroup of patients with MCL, BR produces a significantly higher CR rate (51% vs 24%). High ORRs were attained in both treatment groups. The AE profile of BR was distinct from that of R-CHOP/R-CVP. Support: Teva Pharmaceutical Industries Ltd. Disclosures: Flinn: Teva Pharmaceuticals : Research Funding. Off Label Use: Bendamustine is FDA-approved for adults with chronic lymphocytic leukemia or indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Van der Jagt:Celgene: Consultancy, Research Funding, Sponsorship Other; Novartis: Consultancy, Research Funding, sponsorship, sponsorship Other; Roche: Consultancy, sponsorship, sponsorship Other; Cephalon: Consultancy, Research Funding; Incyte: Research Funding; Xanthus: Research Funding; Bristol-Myers Squibb : Consultancy. Kahl:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. MacDonald:Lundbeck: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Munteanu:Teva Pharmaceutical Industries Ltd.: Employment. Clementi:Teva Pharmaceutical Industries Ltd.: Employment. Chen:Teva Pharmaceutical Industries Ltd.: Employment. Burke:Spectrum Pharmaceuticals: Consultancy.

scholarly journals A Retrospective Multicenter Study to Evaluate the Efficacy of Rabbit Antithymocyte Globulin (rATG) Immunosuppressive Therapy As First-Line Treatment of Aplastic Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1217-1217
Author(s):  
Suporn Chuncharunee ◽  
Raymond SM Wong ◽  
Ponlapat Rojnuckarin ◽  
Cheng-Shyong Chang ◽  
Kian Meng Chang ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Antithymocyte Globulin ◽  
Dose Range ◽  
Recommended Dose ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
The Us ◽  
First Line Treatment

Abstract Background Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine is the preferred treatment for patients with severe acquired aplastic anemia (SAA) ineligible for hematopoietic stem cell transplantation. In 2007, horse ATG (hATG) was removed from most markets outside the US limiting patients to the use of rabbit ATG (rATG). Response rates for hATG range from 60-70%, with overall survival (OS) rates of 60-90% (Korean J Intern Med. 2014;29:713-726). Although, many studies have shown no differences in efficacy between ATG types, others have shown rATG to be inferior to hATG. A prospective study by the US National Institutes of Health (NIH) showed a 6-month RR of 37% for rATG compared to 68% for hATG (N Engl J Med. 2011;365:430-438). The discrepancies in efficacy could be due to many factors including dose and ethnicity. We aimed to analyze hematologic response, survival, and safety of rATG (Thymoglobulin®) as first-line therapy of SAA and very SAA (vSAA) in Asian patients of all ages. Methods We retrospectively reviewed the medical records of 97 consecutive patients who received rATG in combination with cyclosporine and/or a corticosteroid as first-line treatment of SAA or vSAA at participating centers in Malaysia, Taiwan, Hong Kong, and Thailand between 2006 and 2012. The primary endpoint was overall RR (ORR) (complete response [CR] plus partial response [PR]) at 6 and 12 months for patients receiving rATG within the recommended dose range (2.5-3.75 mg/kg/day). Response was evaluated using British Guidelines (Br J Haematol. 2009;147:43-70). Secondary endpoints included ORR in patients receiving any dose of rATG, 2-year OS, OS in responders vs non-responders, relapse rate, and safety. Response and survival with 95% confidence intervals (CI) were estimated using the Kaplan-Meier method. Results Patient median age was 31 years (range 2-81 years); 51% (n= 49) were male and 49% (n=48) female. Eighty-seven percent (n=84) were diagnosed with SAA and 13% (n=13) with vSAA. Twelve patients were excluded from the response evaluation due to the following: lack of post-baseline response data, n=6; second-line rATG within 3 months of first-line treatment, n=3; did not meet criteria for SAA, n=3. Of the 85 patients evaluable for response, only 73% (n=62) received rATG within the recommended dose range; 20% (n=17) received < 2.5 mg/kg/day and 7% (n=6) received > 3.5 mg/kg/day. For patients who received rATG within the recommended dose range, 6- and 12-month ORR were 17.4% (95% CI, 9.8-30.0) and 63.6% (95% CI, 49.4-77.7), respectively. For patients who received any dose of rATG, 6- and 12-month ORR were 24.3% (95% CI, 16.2-35.4) and 68.6% (95% CI, 56.9-80.1), respectively. The 2-year OS rate was 86.3% (95% CI, 77.0-92.0). For patients with a response to treatment (n=46), the 2-year OS was 97.7% (95% CI, 84.6-99.7) compared to 78.9% (95% CI, 59.9-89.6) for patients with no response (n=39), P =.006. The 2-year rate of relapse rate was 6.3% (95% CI 2.1-18.2). The most common serious adverse events (≥ 5%) that occurred within 30 days of last treatment were febrile neutropenia (28%), sepsis (12%), pyrexia (5%), and pneumonia (5%). Grade 4 infusion-related reactions occurred in only 1 (1%) patient. Conclusions Although the 6-month ORR for rATG was low compared to hATG in the NIH study, the 12-month ORR and 2-year OS were comparable to historical results obtained with hATG, suggesting that more time may be needed to achieve maximal response with rATG. Our results show that rATG is an effective form of IST in the Asian population with over 60% of patients achieving a CR or PR at 12 months and an overall survival rate of 86.3% at 2 years. Disclosures Wong: GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding; Pfizer: Research Funding; Roche: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Merck Sharp & Dohme: Research Funding; Biogen-Idec: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Rojnuckarin:Sanofi: Research Funding. Chang:Novartis: Honoraria.

scholarly journals Analysis of Factors Predictive of Risk of Transformation and Time to Transformation in Patients (pts) with Mantle Cell Lymphoma - Cohort Study of 369 Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1526-1526
Author(s):  
Preetesh Jain ◽  
Rashmi Kanagal-Shamanna ◽  
Chi Young Ok ◽  
Gonzalez-Pagan Omarya ◽  
Lucy Navsaria ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Advisory Board ◽  
Initial Diagnosis ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Ki 67 ◽  
Leukemic Phase ◽  
First Line Treatment

Introduction: A fraction of pts with classic variant MCL can transform to an aggressive histology (blastoid/pleomorphic) MCL. Outcomes of transformed pts are inferior to that of denovo blastoid variant MCL and classic variant MCL who never transformed (CNT) Jain P et al ASH 2018. Application of routinely available clinical variables at initial diagnosis to predict the future risk for transformation or time to transformation is an unmet need in MCL. Methods: We analyzed charts from 369 pts with MCL (293 were CNT and 76 were transformed MCL). Statistical analysis was performed from baseline pt characteristics collected from the time of initial diagnosis in CNT group and at the time of initial diagnosis of classic variant MCL who later transformed (t-MCL). Time to transformation (TTT) was calculated from initial diagnosis to the date of transformation in those who transformed and last follow up in those who never transformed. Univariate and multivariate logistic regression modeled the risk of transformation. Classification and regression tree (CART) analysis was performed to identify optimal cut off in categorical variables predictive of TTT. Results: Among the 369 pts, the median age was 62 yrs (range 34-90), 79% were males. Ki-67% values were available in 133 pts (36% of total) and median Ki-67% was 25% (range 1-80). 84% had initial bone marrow involvement and 12% had leukemic phase at diagnosis. The median follow up was 58.5 months and the median overall survival (OS) was 94.8 months and 47% were alive at the time of this analysis. Compared to pts in the CNT group, pts in t-MCL group exhibited differences in following baseline characteristics - higher values of median Ki-67% (30% vs 20% in t-MCL; p=0.04), higher LDH levels, higher proportions of pts with high risk simplified MIPI risk score, leukemic phase at initial diagnosis, complex karyotype and lower hemoglobin and lower proportion of pts achieving complete remission (CR) after first line treatment (78% in t-MCL vs 86% in CNT). In addition, first line treatments received by both groups were similar - R-HCVAD based, R-chemo based, ibrutinib based, chemotherapy alone and miscellaneous. Logistic regression model showed factors associated with the risk of transformation. In univariate analysis, higher risk was significantly associated with Ki-67% as a continuous variable - OR 1.03 (95% CI 1.01-1.05; p=0.006), leukemic phase at diagnosis, high risk MIPI score, complex cytogenetics. First line treatment with ibrutinib compared to R-HCVAD, autologous stem cell transplant SCT at any time point and higher number of nodal sites were associated with decreased risk of transformation. In multivariate analysis (MVA), higher number of nodal sites and SCT were associated with decreased risk of transformation. The median time to transformation in months for those who transformed was 39 (range 5-240 months) while in CNT it was 51 months (1-257 months). We further identified that incremental Ki-67% was significantly associated with TTT and OS (Figure-1A-B). Using CART analysis we identified Ki-67% ≥60 is significantly associated with shorter TTT (HR, 6.26; 95% CI 2.58-15.21; p &lt;0.001-1C). In addition, shorter TTT was associated with elevated LDH, high risk MIPI score, CNS involvement at baseline, higher WBC counts, leukemic phase MCL, complex cytogenetics and R-chemotherapy as first line treatment while longer TTT was associated with higher number of nodal sites, SCT at any time point, higher hemoglobin, CR after initial treatment (Figure-1D) and increased number of lines of treatment before transformation. In MVA, higher number of nodal sites, CR after initial treatment was predictive of longer TTT while CNS involvement at baseline and bone marrow involvement at baseline were predictive of shorter TTT. Further analysis on gene signature, type of treatments, response, VH gene mutation, Sox-11 status, somatic mutation status are ongoing and will be reported. Conclusions: This is the first analysis showing an association of routinely available clinical variables in determining risk for transformation of MCL and TTT. Routinely available variables such as incremental Ki-67%, LDH levels, number of nodal sites, ibrutinib based treatments, SCT, CR after first line treatment and leukemic phase at diagnosis reliably predicted for time to transformation in MCL. Disclosures Lee: Seattle Genetics, Inc.: Research Funding. Westin:Genentech: Other: Advisory Board, Research Funding; Curis: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Celgene: Other: Advisory Board, Research Funding; Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; Unum: Research Funding; 47 Inc: Research Funding; MorphoSys: Other: Advisory Board; Janssen: Other: Advisory Board, Research Funding. Nastoupil:Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Spectrum: Honoraria. Champlin:Sanofi-Genzyme: Research Funding; Actinium: Consultancy; Johnson and Johnson: Consultancy. Neelapu:Cellectis: Research Funding; Novartis: Consultancy; Precision Biosciences: Consultancy; BMS: Research Funding; Acerta: Research Funding; Incyte: Consultancy; Poseida: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Cell Medica: Consultancy; Karus: Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Allogene: Consultancy. Fowler:TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: 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; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria; MoreHealth: Consultancy, Equity Ownership; Pharmacyclics: Honoraria, Research Funding; Acerta Pharma: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding.

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