Effectiveness and Cost of Rituximab for CLL in the Province of Manitoba Prior to Its Approval As Part of First Line Treatment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4701-4701
Author(s):  
Pamela Skrabek ◽  
Rajat Kumar ◽  
James B Johnston ◽  
Joseph Baptiste ◽  
Bernie Lozar ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Clinical Outcomes ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
The Third ◽  
Treatment Line ◽  
Oncology Drug ◽  
First Line Treatment

Abstract Abstract 4701 Introduction: In Manitoba (MB), population 1.25 million, utilization of parenteral oncology drugs is captured through a provincial oncology drug program (PODP) database. The MB Oncology Drug Utility and Clinical Outcomes Program (MODUCO) evaluates drug/regimen utilization with correlation to clinical outcomes. Rituximab (R) accounts for a significant proportion of PODP expenditures, as such monitoring effectiveness at the population level is essential. First line treatment of CLL with FR or FCR was approved in MB in 2009. Prior to this, approval for R based regimens required a non-formulary request. This was a MODUCO initiative to determine effectiveness and cost of R based therapy for CLL in MB, prior to formulary approval of R as part of first line treatment. Methods: Using the PODP database all patients in MB with CLL (and SLL) who received any form of R based therapy between January 14, 2003 and December 14, 2007 were identified. Using this cohort, treatment with R based regimens up until March 14, 2011 was analyzed with follow up until August 1, 2012. Treatment with R for transformed lymphoma was excluded. The primary outcome measure of Treatment Free Survival (TFS) was defined as the interval from initiation of R to next treatment or death. Patients were censored if alive without further treatment at the date of last follow up. The following factors were analyzed for impact on TFS: age, gender, treatment line (greater than or equal to 1), R treatment line (greater than or equal to 1), regimen, treatment indication (symptomatic disease, lymphocyte doubling time (DT), autoimmune cytopenias, or stage 3/4 disease) and response (No /Yes). Response was defined as improvement in peripheral blood counts or reduction in lymphadenopathy and/or organomegaly. Exact dose of R received during each treatment was recorded for cost analysis. Results: Between 2003–2007 R based therapy was administered for the first time to 86 patients (57 males) with mean age 65.1 years. Median number of prior treatments was 3 (range 1–9). Second time treatment with R was given to 40 patients (46.5%) while 12 (14%) received R on three or more occasions during the follow up period. Overall response was seen in 72.4%. The median time to next treatment or death (TFS) was 1.28 years (95% CI 1.01–1.64) with 50 deaths. Factors contributing to shorter TFS based on univariate analysis were (a) lack of response (p<0.0001), (b) 2nd or 3rd time R administration (p 0.04 and 0.0002), and (c) use of RCVP or RCHOP (p <0.02) or other regimens (p <0.001) compared to the reference (FR/FCR). Multivariate analysis revealed that treatment initiation due to DT, compared to all other indications, was associated with decreased rate of retreatment or death (HR 0.36, 95% CI 0.17–0.73). As seen in Figure 1, patients receiving R for the third time (or greater) had shorter median TFS (HR 2.54, 95% CI 1.48–4.36). Regimens other than FR, FCR, RCVP, RCHOP and RCD had increased risk of needing alternative treatment or dying (HR 1.82, 95% CI 1.08–3.06). Mean cost of R per regimen was $12,999.91. The total cost of R for this cohort was $1.87 million. Cost of R when used for the third time or greater was $410,698. Conclusion: This population-based retrospective analysis of cost and effectiveness of R, prior to formulary inclusion for CLL, reveals that patients derive maximum benefit with 1st and 2nd administration of R. These patients had refractory or relapsed disease with multiple prior treatments, yet a high proportion responded to treatment confirming the utility of R for salvage therapy. Duration of response is an important consideration in cost-effectiveness, with the MODUCO experience suggesting that effectiveness diminishes with non-standard regimens and greater than 2 previous R containing regimens. Improving patient access to treatments in health care systems that are publically funded means balancing cost with effectiveness in the population. Disclosures: Kumar: Celgene: Membership on an entity's Board of Directors or advisory committees. Johnston:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bourrier:Roche: Grant Funding for Educational Initiatives Other.

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.

scholarly journals Combining Imatinib-Following-Nilotinib Treatment in First Line Therapy for Chronic Phase Chronic Myeloid Leukemia. Update from the PhilosoPhi34 Study at 24 Months of Follow-up

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5435-5435
Author(s):  
Maria Luisa Pioltelli ◽  
Ester Pungolino ◽  
Mariella D'adda ◽  
Chiara Elena ◽  
Lorenza Maria Borin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Sokal Score ◽  
First Line Treatment

Abstract Background Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder which molecular base is represented by the bcr-abl fusion gene, encoding for the constitutionally activated BCR-ABL tirosine-kinase. Three Tirosin-Kinase Inhibitors (TKI) are approved for first line treatment: Imatinib (IM) and the second generation (2G) TKI Nilotinib (NIL) and Dasatinib. 2G TKI are known to provide faster and deeper molecular responses (MR) compared to Imatinib, but serious toxicities may hamper long term treatment with these molecules. Furthermore, 2G TKI were usually employed as second line after IM failure, while the inverse sequence from second to first generation TKI (like an induction-maintenance model) has not been explored yet. We used this schedule in a small group of patients in the PhilosoPhi34 study (EudraCT: 2012-005062-34), a clinical trial designed by the REL (Rete Ematologica Lombarda) cooperative group. This study was composed by three consecutive phases: a Recruitment Phase, a Core Phase (CP) in which patients received NIL 300 mg BID for 12 month (mos), and an Observational Phase (OP), restricted for patients who obtained at least complete cytogenetic response at the end of the CP. During OP, treatment choice was up to the physician and any TKI approved for first line treatment could be used, including IM. In 2017 we presented preliminary data showing that a 12-mos-NIL treatment followed by IM appears as a safe and effective choice for first line therapy in chronic phase CML. Fluctuations in BCR/ABL ratio were similar between IM and NIL treated pts, and the probability of loss of MR4 or MR3 was the same in the two groups; furthermore, despite fluctuations, MR was maintained or improved over time in IM subgroup. Our purpose is to verify these data after 24 mos follow up (FU) at the end of OP. Methods We analyze PhilosoPhi34 database; MR is reported at 3, 6 and 12 mos during the CP and every 6 mos during the OP. The last pt completed the 24 mos of OP in June 2018. Database is still open, evaluations ongoing, and some data can be missing yet: our preliminary observations concern pts with available data of 24 mos OP. Results Seventy-nine pts started the OP. Fourteen pts switched to IM during the OP (Table 1) due to high cardiovascular risk or grade 1-2 chronic AEs . Only 11 pts started IM since the beginning of OP, and we consider these pts in our analysis. Sokal score was high in 2 pts (18%), intermediate in 5 (45.5%), low in 4 (36.5%). At the beginning of OP, 6 pts had a MR ≥ 4 (54.5%), 5 had MR3 (45.5%). At 12 mos of the OP, 7 had MR ≥ 4, 3 had MR3 and 1 had lost MR3 with PCR 0.192%IS (1/5, 20%). At 24 mos of the OP, 9 had MR ≥ 4 (81,8%), and 2 had MR3. Notably, none of pts lost MMR; 2/3 pts(66%) improved response from MR 3 to MR 4 and the pt who transiently lost MMR at 12 mos, recovered it at 24. Sixty-four pts maintained 2G TKI: 62 NIL, 2 other TKI (not considered for analysis). Of them, 4 were lost during this phase: 2 within the first year of OP, other 2 within 12 and 24 mos of OP. In the NIL group, Sokal score was high in 10 pts (16.6%), intermediate in 19 (31.6%) and low in 31 (51.6%). At the beginning of OP, 32 pts had MR ≥ 4 (51.6%), 21 had MR3 (33.8%) and 9 less than MR 3 (14.5%). Responses were improved over time: at 12 mos, 36 pts had MR ≥ 4 (60%), 20 had MR3 (33%) and 4 less than MR3 (6%). At 24 mos 46 pts had MR ≥ 4 (78%), 8 MR3 (13.5%) and 4 less than MR3 (8,5%), Among them, 1 pt experienced disease progression due to a mutation. In particular, during the second year of OP, 11 pts improved response from MR3 to MR ≥ 4(11/20, 55%). Discussion Our data show progressive MR improvement in both IM and NIL group. In particular, risk of loss of MMR is not increased in IM group. More data, more balanced groups and a longer FU are necessary to further confirmations, but after three years of FU, we consider this combination of NIL-followed-by-IM a possible strategy for first line treatment in chronic phase CML, in particular for pts with cardiovascular risk factors. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

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 &lt; 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 Prognostic Comparison Between ISS and R-ISS in Real-Life Setting of Myeloma Patients: An Example of Utilization of Electronic Biobank Database

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5645-5645
Author(s):  
Samu Kurki ◽  
Klaus Tamminen ◽  
Tatu Miettinen ◽  
Kari Remes
Keyword(s):  
Board Of Directors ◽  
Real Life ◽  
Hazard Ratio ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Kaplan Meier ◽  
Real Life Setting ◽  
First Line Treatment

Abstract Introduction: Identification of patients with high-risk (HR) multiple myeloma (MM) is important to optimise their treatment. In 2015, revised International Staging System (R-ISS) guidelines were published (Palumbo, 2015) where HR cytogenetics (CG) and elevated serum lactase dehydrogenase (LDH) were added to the traditional ISS staging criteria. Thus, R-ISS stage III includes one of the HR CG abnormalities or elevated LDH, ISS stage I patients have no HR CG and normal LDH; the rest of patients belong to R-ISS stage II. There are limited data on the prevalence of R-ISS groups in comparison to the old ISS grouping and impact on clinical outcomes in the real-life setting. The aim of the present analysis was to use structured longitudinal electronic health records (EHR) provided by the Finnish Auria Biobank to compare the prevalence and survival outcome between patients in ISS and R-ISS groups in a real-life patient cohort of 100 patients treated at Turku University Hospital. Auria Biobank covers roughly 15% of the population of Finland and collects samples with the associated data from all diseases treated at Turku University Hospital based on the Finnish Biobank Act. Methods: Auria Biobank database was analysed retrospectively for all MM-patients diagnosed between 2008-2013 (incident cohort) and whose fluorescence in situ hybridization analysis was performed at the time of diagnosis. Data for age, gender, LDH, creatinine, ISS, R-ISS, CG, time to next treatment and overall survival were collected from Auria Biobank. Classification into ISS groups was done based on data at the time of diagnosis and OS. Classification into R-ISS staging was done according to IMWG (Palumbo, 2015). For HR CG at least one of the following CG abnormalities was required: del(17), t(4:14), or t(14:16). Estimated glomerular filtration rate was calculated by using the CKD-EPI formula. Drug treatments were classified as conventional (e.g. melphalan + prednisolone) or novel (proteasome inhibitors, IMIDs). Descriptive methods and Kaplan-Meier survival analysis were used for comparison of the groups. Results: The median age of the 100 patients was 64 yrs (range: 37 - 80), and 43% were female. At the time of diagnosis, 17% of patients had high risk CG status, 32% had at least moderate kidney failure (estimated glomerular filtration rate <60ml/min) and 26 % had elevated LDH. 41% patients received autologous stem cell transplant and 64% and 14% were treated with novel and conventional treatments in first line, respectively. 26%, 48% and 26% were classified to ISS stage I, II and III groups respectively, and 21%, 63% and 16% to R-ISS stage I, II and III groups, respectively. Criteria to include patients into R-ISS III were HR CG in 62 %, elevated LDH in 69 % and 31 % fulfilled both criteria. Neither ISS- nor R-ISS staging had any influence on first line treatment decisions between novel and conventional treatments. In all patients 2-year OS (from diagnosis) was 82% (median OS not yet reached). The 2-year OS in ISS I, II and III groups was 90%, 88%, and 60% respectively, and in R-ISS I, II and III groups 87%, 85% and 42%, respectively. R-ISS had a statistically significant effect on survival time (log rank P=0.032), with R-ISS III patients having a 3.8-fold risk of death compared to R-ISS I (Fig 1). R-ISS III patients had also shorter (ns) treatment free survival than R-ISS I patients (HR 2.1, log rank P=0.479) (Fig 2). No statistically significant difference was observed between the survival curves stratified by ISS staging groups. Conclusion: The new R-ISS staging system, using additional information including CG-profile and serum LDH, separated in our real-life setting more profoundly patients with poor prognosis than the old ISS staging. Structured EHRs can successfully be used to derive useful clinical and prognostic data from real-life MM patients. Figure 1 Kaplan-Meier curves for overall survival in different R-ISS groups. Time is measured from diagnosis to death or end of follow-up. Log rank P=0.032. R-ISS III vs. R-ISS I hazard ratio 3.8. Figure 1. Kaplan-Meier curves for overall survival in different R-ISS groups. Time is measured from diagnosis to death or end of follow-up. Log rank P=0.032. R-ISS III vs. R-ISS I hazard ratio 3.8. Figure 2 Kaplan-Meier curves for time to next treatment in different R-ISS groups. Time is measured from beginning of first line treatment to beginning of second line treatment or end of follow-up. Log rank P=0.479. R-ISS III vs. R-ISS I hazard ratio 2.1. Figure 2. Kaplan-Meier curves for time to next treatment in different R-ISS groups. Time is measured from beginning of first line treatment to beginning of second line treatment or end of follow-up. Log rank P=0.479. R-ISS III vs. R-ISS I hazard ratio 2.1. Disclosures Tamminen: Aava Healthcare group: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Roche: Employment; Takeda: Employment. Remes:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees.

PET/CT Is a Useful Tool For Both Refining The Definition Of Complete Response (CR) In Multiple Myeloma (MM) and Detecting Otherwise Unrevealed Progression During The Follow-Up Of The Disease: A Single Centre Experience On 282 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1936-1936 ◽  
Author(s):  
Elena Zamagni ◽  
Cristina Nanni ◽  
Annalisa Pezzi ◽  
Katia Mancuso ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Pet Ct ◽  
Prognostic Groups ◽  
Definition Of ◽  
First Line Treatment

Abstract PET/CT is a reliable technique for assessing skeletal involvement in MM and a valuable tool at the onset of the disease for predicting outcomes in those patients who are eligible to subsequently receive autologous stem cell transplantation (ASCT). However, the prognostic role of PET/CT after treatment and/or during the follow up of the disease, as well as in the non ASCT setting, still remains less defined. To address these issues, we retrospectively analyzed 282 symptomatic MM pts, with a median age of 58 yo, (range 22-83), who were diagnosed and treated in a single institution between 2002 and 2012, and were followed for a median of 66 months. Treatment included ASCT in 70%, novel agents in 77% and was bortezomib-based in 37% of the cases. All the pts were studied with PET/CT at baseline, then every 12-18 months during follow-up, and at the time of each subsequent relapse; for 189 of them PET/CT scans at baseline and 3 months after the end of first line treatment were available. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FLs), their associated standardized uptake value (SUVmax) and presence of extra-medullary disease (EMD) were recorded. Forty two percent of the pts at diagnosis had > 3 FLs and in 50% of them SUVmax was > 4.2; EMD was present in 5% of the cases. On multivariate analysis, these 3 variables adversely affected PFS and OS, and retained prognostic relevance independently of the treatment received (including or not ASCT, bortezomib- or non-bortezomib-based). On multivariate analysis, ISS stage 3, presence of >3 FLs at PET/CT and failure to achieve CR during or after first line treatment were the leading factors independently associated with shorter PFS and OS. These 3 variables enabled the definition of a scoring system, based on the number of risk factors simultaneously present (score 0: none of the 3 adverse factors, 31% of the pts; score 1: only one out of the 3, 37%, score 2+: 2 or 3 factors, whatever of them, 32% ), that predicted for PFS and OS. More specifically, median PFS was 36 months (mos) for pts with score 0, 58 mos for score 1 and 74 mos for score 2+ (P=0.000). OS was also significantly influenced by the number of adverse factors, with a progressive increase in hazard ratios. A similar stratification into 3 prognostic groups was obtained when SUVmax > 4.2 and presence of EMD replaced FLs>3 within the scoring system. After treatment, PET/CT negativity (PET-CR) was observed in 70% of the pts, while conventionally-defined CR was achieved in 53% of them. Attainment of PET-CR favorably influenced PFS and OS, both in uni and multivariate analyses. Notably, 29% of the pts who achieved CR according to conventional criteria still had positive PET/CT scans: their median PFS was 50 mos as compared with 90 mos for those pts who also achieved PET-CR (P= 0.01) (fig. 1). OS was significantly inferior, as well, for pts not achieving PET-CR, with 6-year estimate of 65% in comparison to 90% for PET negative pts (P=0.0035) (fig. 1). On multivariate analysis, PET-CR was an independent factor predicting for prolonged PFS (P= 0.004) and OS (P= 0.02) within the conventionally-defined CR group. Sixty three percent of the pts experienced relapse or progression, after a median of 56 mos from the end of first-line treatment. In 37% of them, progression was only serological, both serological and skeletal in 48%, only skeletal in 15% and in 12% of these latter patients it was exclusively detected by systematic PET/CT during the follow-up (no pain or pathological fractures). A logistic regression analysis of baseline and post treatment features revealed that persistence of SUVmax > 4.2 after the end of first line treatment was independently associated with exclusive PET/CT progression. In conclusion, PET/CT was confirmed as a reliable predictor of outcome in newly diagnosed MM pts, whatever the treatment. PET/CT combined with ISS stage and attainment of CR to first line therapy was able to split pts in different prognostic groups. Importantly, PET/CT contributed to a more careful and deep evaluation of CR, going beyond the conventionally defined level, and should thus be recommended as a complementary tool to define “true” CR. Finally, in pts with a persistent high glucose metabolism after first line treatment, PET/CT can be recommended during the follow-up, in order to point out possible progression, not otherwise identifiable. Disclosures: Zamagni: Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Consultancy, Honoraria, 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; Millennium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

scholarly journals The Prognostic Utility of Serial MASS-FIX in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1619-1619
Author(s):  
Nadine Abdallah ◽  
David L Murray ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Disease Progression ◽  
Board Of Directors ◽  
Research Funding ◽  
Disease Monitoring ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Immunofixation Electrophoresis ◽  
First Line Treatment

Abstract Background: MASS-FIX is a novel method for detection, characterization and quantification of serum and urine monoclonal proteins in multiple myeloma (MM) which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). MASS-FIX has been endorsed by the International Myeloma Working Group (IMWG) as an alternative to immunofixation electrophoresis for diagnosis and disease monitoring in MM and has replaced immunofixation electrophoresis in our institution. This technique has demonstrated superior sensitivity and specificity compared to conventional gel-based methods, but its prognostic value is still unknown. We designed this study to evaluate whether serum M protein monitoring by MASS-FIX has prognostic significance in predicting disease progression in patients with MM. Methods: In the first part of the study, we included patients with MM who had a documented negative MASSFIX after first-line treatment and had serial MASS-FIX data available (n=187). We then compared the time to next treatment (TTNT) between patients who became positive by MASS-FIX and those who remained negative by last follow up. In the second part, we included patients who were positive by MASS-FIX within 90 days from diagnosis and had available serial MASS-FIX data (n=203). We compared TTNT between patients who became negative by MASS-FIX and those who remained positive by last follow up. TTNT was defined as the time of initiation of the first-line treatment to the time of initiation of second-line treatment or last follow up. Results: Part 1: We included 155 patients diagnosed with MM between January 2013 and December 2019 who had a documented negative MASSFIX with first-line treatment and had serial MASSFIX data available. After a median follow up of 3.1 (95%CI: 2.6-3.5) years, 44 (28%) patients became MASSFIX positive, while 111 (72%) still had negative MASS-FIX. The median time from treatment start to negative MASSFIX was 18.0 (IQR: 6.4-33.5) months. The median TTNT was 4.1 (95%CI: 3.2 - NR) years in patients who became MASSFIX positive and not reached (NR) (95%CI: NR-NR) in patients who were MASS-FIX negative by last follow up (P&lt;0.001). The 2-year OS was 97% and 100% in the 2 groups, respectively (P=0.27). Part 2: We included 203 patients who had positive MASSFIX within 90 days from diagnosis and available serial MASSFIX data. The median follow-up was 1.5 (95%CI: 1.5-1.7) years. By last follow up, 39 (19%) patients became MASSFIX negative while 164 (81%) still had positive MASSFIX. The median TTNT was NR (95%CI: 2.0-NR) years in patients who developed negative MASSFIX and 2.3 (95%CI: 1.9 - NR) years in patients who were still MASS-FIX positive by last follow up (P=0.03). The 2-year OS was 97% and 94% in the 2 groups, respectively (P=0.84) Conclusion: The utilization of MASS-FIX in disease monitoring of MM patients provides prognostic information; among patients who become MASS-FIX negative after first line treatment, an earlier conversion to positive MASS-FIX predicts disease progression. Similarly, persistent MASS-FIX positivity after treatment initiation predicts earlier disease progression. Larger studies and longer follow up are needed to evaluate whether the MASS-FIX is associated with overall survival. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Sorrento Therapeutics: Consultancy; Oncopeptides: Consultancy; Pfizer: Research Funding; Alnylam: Research Funding; Takeda: Research Funding; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Sanofi: Consultancy; GSK: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Alexion: Consultancy. Kumar: Amgen: Consultancy, Research Funding; Bluebird Bio: Consultancy; Antengene: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Merck: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Novartis: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

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 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) (&lt;2mg/kg) in lower grade aGVHD (grade 2a) and most centers (88%) starting with higher doses (2mg/kg) in aGVHD grades &gt;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 (&gt;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.

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