Retrospective Analysis Of The Recent Treatment Strategies For The Patients With Myeloma-Related Diseases Registered In Kansai Myeloma Forum

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3385-3385 ◽  
Author(s):  
Hirokazu Tanaka ◽  
Satoru Kosugi ◽  
Toru Kida ◽  
Kensuke Ohta ◽  
Ryosuke Yamamura ◽  
...  
Keyword(s):  
Clinical Features ◽  
Research Funding ◽  
Treatment Strategies ◽  
Novel Agents ◽  
The Novel ◽  
Disease Evolution ◽  
Best Response ◽  
Novel Agent ◽  
Better Than

Abstract Introduction There has been dramatic evolution in multiple myeloma (MM) therapy in the last decade. The novel agents (Thal, Bor, and Len) have been reported to improve natural history of the cases with MM. In order to use optimal drugs for each patient, we should investigate the actual conditions of the clinical practice. However, we could not have the information regarding epidemiology, clinical features, treatment results, prognosis, and so on because there is no large-scale database demonstrating the clinical features of MM-related diseases in Japan. Therefore, we have founded the study group, named as Kansai Myeloma Forum (KMF), for the purpose of registering the cases with MM-related diseases in Kansai area of Japan on November, 2012. In this study, we analyzed the clinical characteristics and outcomes of MM-related diseases registered in KMF and evaluated the treatment strategies in the novel agent era. Patients & Results Among a total of 923 cases initially diagnosed since 2006 and registered to KMF database until March 31, 2013, we analyzed 434 symptomatic MM cases (213 females/221 males), who were treated since 2006. The median age was 69 (range: 32-96), and the OS rates at 3 and 5 years were 68.7% and 45.3%, respectively. The prognosis of the cases treated after 2010 became significantly better than that of the cases treated between 2006 and 2009 (log-rank test: P=0.019). The prognosis of the cases treated with the novel agents was significantly better than without them (p=0.005). Among the non-transplanted 339 cases, the effects of the novel drugs were shown more clearly (p=0.002). The best response during the course differentiated the prognosis; the hazard ratios of CR, VGPR, PR, SD and PD compared to sCR were 2.23, 3.19, 9.54, 16.84 and 432.01, respectively (P<0.001). Ninety-five cases received the high-dose melphalan therapy (HD-MEL) with stem cell support. The OS rate of these 95 cases was significantly better than that of non-transplanted 339 cases (90.1% at 3-year/61.4% at 5-year vs. 61.6%/40.2%, p<0.001). CR/sCR rate after HD-MEL was 50%. Also, 83 out of 95 cases received at least one of the novel agents during their clinical courses, and 51 cases achieved CR/sCR as best response, showing significant better survival than the cases with best response of VGPR or <PR (p=0.008). The superiority of OS in HD-MEL group was also observed even when less than 65 years old patients (74 out of 95 patients) were compared to 55 patients (≤ 65 years) without HD-MEL but receiving novel agents (90.6% at 3-year/71.4% at 5-year vs. 73.6%/47.3%, p=0.036). Next, we analyzed 123 cases with MGUS and 54 with smoldering MM (SMM), who had diagnosed in 2006 or later. The median age at diagnosis was 66.0 (range: 34-88) in 123 MGUS cases (53 females/70 males). The type of paraprotein detected was IgA in 15.4% of the cases and IgG in 69.1 %. With a median follow-up period of 27.2 months, 8 cases (6.5%) received chemotherapies due to the disease evolution. The evolution rates at 1, 3 and 5 years after the diagnosis were 2.1%, 9.0% and 12.0%, respectively (2.4% per year). The 3-year OS after the start of treatments was 75.0%. In 54 SMM cases (29 females/25 males), the median age was 68.2 (range: 40-87), and IgG and IgA types comprised 72.2% and 14.8%, respectively. With a median follow-up period of 22.4 months, 15 cases (27.8%) received chemotherapy due to progression to symptomatic MM. The evolution rates at 1, 3 and 5 years after diagnosis were 15.4%, 36.7% and 62.5%, respectively (12.5% per year). The 3-year OS after the start of treatments was 76.9%. Discussion & Conclusion The current study revealed the significant effects of novel agents on symptomatic MM cases in the practical use. It has been still unknown and controversial whether HD-MEL with auto-PBSCT is necessary or not in the novel agent era. In this analysis, it was shown that HD-MEL could provide significant survival benefit to symptomatic MM cases even in the novel-agent era. However, it is necessary to determine when and how we should perform HD-MEL for MM during therapeutic sequences including novel agents. This study also suggested that it might be unnecessary to generally consider an early chemotherapy to MGUS or SMM cases before the evolution, since the prognosis after the evolution seemed not to be inferior to that of the de-novo symptomatic MM. Thus, KMF database would provide abundant and beneficial information to consider the treatment strategies of the cases with MM-related diseases. Disclosures: Tanaka: celgene: Research Funding. Kosugi:Janssen: Honoraria; celgene: Research Funding. Kida:celgene: Research Funding. Ohta:celgene: Research Funding. Yamamura:celgene: Research Funding. Shibayama:Janssen: Honoraria; celgene: Honoraria, Research Funding. Kohara:celgene: Research Funding. Kaneko:celgene: Research Funding. Fuchida:celgene: Research Funding. Kobayashi:celgene: Research Funding. Miyamoto:celgene: Research Funding. Shindo:celgene: Research Funding. Kuroda:celgene: Research Funding. Uoshima:celgene: Research Funding. Matsumura:celgene: Research Funding. Yoshii:celgene: Research Funding. Kamitsuji:celgene: Research Funding. Boku:celgene: Research Funding. Ishii:celgene: Research Funding. Matsuda:celgene: Research Funding. Takahashi:celgene: Research Funding. Hamada:celgene: Research Funding. Adachi:celgene: Research Funding. Nakatani:celgene: Research Funding. Nomura:celgene: Research Funding. Taniwaki:celgene: Research Funding. Takaori:celgene: Research Funding. Shimazaki:celgene: Research Funding. Tsudo:celgene: Research Funding. Hino:celgene: Research Funding. Matsumura:Janssen: Honoraria, Research Funding; celgene: Research Funding. Kanakura:celgene: Research Funding.

Continued Improvement in Survival in Multiple Myeloma and the Impact of Novel Agents

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3972-3972 ◽  
Author(s):  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Morie A Gertz ◽  
Martha Q Lacy ◽  
John A Lust ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Initial Therapy ◽  
Novel Agents ◽  
The Novel ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Past ◽  
The Impact

Abstract Abstract 3972 Background: The treatment paradigm for myeloma has undergone a dramatic shift in the past decade with the introduction of the novel agents and their application at every stage of the treatment. We and others had previously shown that survival of patients with myeloma had improved in the earlier half of the last decade and attributed this to a combination of novel therapies as well as increased use of stem cell transplant. It is not clear if this momentum in improving survival has been maintained. We examined the survival trends of patients with newly diagnosed myeloma seen within the past decade to examine this question. Patients and Methods: We studied 1056 patients with newly diagnosed myeloma, who were seen at Mayo Clinic between January 1, 2001 and December 31, 2010; who were seen within 30 days of their diagnosis. For examination of the time trends, we grouped the time interval into two five year periods, 2001–2005 and 2006–2010. Survival was estimated using Kaplan Meier method and survival curves were compared by log rank test. Impact of various prognostic factors was evaluated using Cox proportional hazards test. Results: The median age at diagnosis was 65 (range; 22–92), and 59% were male. The median estimated follow up for the entire cohort was 4.6 years (95% CI; 4.4, 4.9) and 57% of the patients were alive at last follow up. The median overall survival (OS) for the entire cohort was 5.4 years (95% CI; 5, 6.3). The overall survival for patients in the 2001–2005 group was 4.6 years compared with not reached for the 2006–2010 cohort (P< 0.001). The five-year estimated OS was 48% for the earlier group compared with 66% for the latter group. The estimated 1-year survival was 90% for the recent cohort compared with 83% for the earlier cohort, suggesting improvements in the early mortality. Interestingly, the improvement was predominantly seen in the older age group (>65 years; 49%). The 5-year survival of the older patients improved significantly from 31% (2001–2005) to 56% (2006–2010) (P<0.001). In contrast, among younger patients (≤65 years of age), the 5-year survival improved only marginally from 63% (2001–2005) to 73% (2006–2010) (P=NS). One or more novel agents (Lenalidomide, thalidomide or bortezomib) were used as part of initial therapy in 631 (62% of 1021 in whom treatment data was available). The OS among of this group was 7.3 years (95% CI; 5.9, NR) compared with 3.8 years (95% CI; 3.1, 4.6). In a multivariate model that included both use of novel agent and the year group, only the novel agent use was associated with improved survival suggesting that the improvement in the survival is related to the increased use of novel agents in the initial therapy. No significant differences were observed between the groups in terms of conventional prognostic factors. Conclusions: The current results confirm continued improvement in the overall survival of patients, even within the last 10 year period, and highlight the impact of initial therapy with novel agents. Most importantly, we demonstrate that the improved survival has primarily benefited older patients. Our study highlights that urgent need for additional new agents to provide further survival improvement for younger patients, and in order achieve a cure for this disease. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Cephalon: Research Funding; Genzyme: Research Funding. Dispenzieri:Celgene: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Janssen Research & Development: Research Funding. Gertz:Binding Site: Honoraria.

The Impact of Induction Regimen Choice on Transplant Outcome and Survival in Newly Diagnosed Multiple Myeloma in the Era of Novel Agents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3044-3044
Author(s):  
Rajshekhar Chakraborty ◽  
Shaji Kumar ◽  
Francis Buadi ◽  
David Dingli ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Novel Agents ◽  
Agent Based ◽  
Induction Regimen ◽  
Baseline Characteristics ◽  
The Impact ◽  
Novel Agent

Abstract Background Induction with novel agents, including proteasome inhibitors and immunomodulators, prior to autologous stem cell transplantation (ASCT) is the standard of care frontline treatment of transplant-eligible patients with multiple myeloma (MM). Common novel agent-based induction regimens include three drug combinations with a backbone of bortezomib (V), thalidomide (T) and/or lenalidomide (R). There is limited information on the comparative efficacy of novel regimens used as part of initial therapy prior to an ASCT in terms of overall survival (OS). To address this question, we retrospectively analyzed 1096 consecutive patients undergoing ASCT for MM at Mayo Clinic. Methods Study patients included those who underwent first transplant within 12 months of diagnosis, did not receive more than one induction regimen, did not relapse prior to transplant and did not receive treatment for smoldering MM in the past. Baseline characteristics, response rates and survival data were extracted from an electronic medical record and statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Choice of induction regimen was almost exclusively made by the referring physician. Results Median age at diagnosis was 60.3 years (Interquartile range 53.9-65.9). ISS staging at diagnosis was available for 49.7% of patients, of which, 34.2%, 39.3% and 26.5% of patients had ISS stage 1, 2 and 3 disease, respectively. Estimated median follow up was 65.6 months (95% CI 58.3-73.3). Baseline characteristics of patients by initial treatment have been summarized in table 1. Major subgroups by induction therapy included patients receiving Cy-Bor-d (n=193, 17.6%), Vd (n=64, 5.83%), Rd (n=253, 23.1%), VRd (n=126, 34.6%), Td (n=157, 14.3%) and VAD or dexamethasone alone as the non-novel agent comparator group (n=229, 20.9%). Median overall survival (OS) was significantly different between novel agent-based and conventional regimens (Log-rank test; p=0.0029), which were 102.7 months (95% CI, 95.2-112.2) and 78.8 months (95% CI, 67.8-92.6) respectively. Median OS with each regimen is shown in table 1. Among novel agent-based regimens, there was no significant difference in median OS, except Td, which was inferior to Rd (HR 1.62; 95% CI 1.17-2.24). Conclusion We cannot demonstrate with overall survival as an endpoint that the doublets of Vd and Rd are inferior to VRd or Cy-bor-d. There were insufficient patients treated with VTd to be included. Our study shows that the choice of novel induction regimen prior to ASCT does not affect survival (with the exception of Td being inferior to Rd), reflecting the wide array of effective salvage options. However, further prospective randomized clinical trials comparing these regimens are required to validate these findings. Table 1. Baseline characteristics and overall survival. Baseline characteristics and survival Cy-Bor-d (n=193) Vd (n=64) Rd (n=253) VRd (n=126) Td (n=157) VAD or Dex (n=229) p-value Median age 61.9 62.15 60.8 60.8 59.3 58.5 0.0041 Sex (percent males) 56.48 57.81 56.92 61.91 57.96 59.82 0.9271 ISS at diagnosis 1:24.82% 2:40.69% 3:34.48% 1:29.73% 2:24.32% 3:45.94% 1:40% 2:43.78% 3:16.22% 1:41.76% 2:34.06% 3:24.18% 1:28% 2:36% 3:36% 1:20% 2:60% 3:20% 0.0005 Median follow-up (95% CI) 20.3 (17.1-22.7) 49.5 (44.7-55.7) 59 (54.5-67) 26.9 (22.8-30.7) 126.7 (120.2-132.9) 143.4 (132.5-152.6) <0.0001 Median OS Not reached (Estimated 5 year OS rate 75%) 97.2 months (95% CI, 66.6-NR) 112 months (95% CI, 97.4-124.3) Not reached (Estimated 5-year OS rate 77%) 81.1 months (95% CI, 59.1-99.1) 78.8 months (95% CI, 67.8-92.6) 0.0019 Figure 1. Figure 1. Disclosures Kumar: Onyx: Consultancy, Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria.

Outcomes of Elderly cHL Patients in the Novel Agent Area: Improved Survival Since 2011 in the SEER-Registry Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Harsh Shah ◽  
Seongho Kim ◽  
Hyejeong Jang ◽  
Ahmad S Halwani
Keyword(s):  
Risk Factors ◽  
Sensitivity Analysis ◽  
Age At Diagnosis ◽  
Novel Agents ◽  
Stage Iii ◽  
The Novel ◽  
Factors Associated ◽  
Registry Analysis ◽  
Novel Agent

Background: Classical Hodgkin Lymphoma (cHL) patients that are older than 60 years have worse survival compared to those that are younger due to aggressive biology and treatment-related toxicities. Approval of novel agents such as brentuximab (2011) and checkpoint inhibitors (2016) in the relapsed/refractory setting has changed the treatment paradigm of cHL. To assess the effect of novel therapeutic agents on the survival of elderly cHL patients over time, we conducted a SEER 18 registry analysis (released Nov 2018) of cHL patients greater than 60 year old and compared outcomes of those diagnosed between 2006-2010 (before approval of novel agents) to those diagnosed between 2011-2015 (novel agent era). Methods: Patients from SEER 18 registry (released Nov 2018) with cHL and age 60 or greater were included in this study. Cohort 1 included patients from pre-novel agent era (diagnosed from 2006-2010) and cohort 2 included patients from novel agent era (diagnosed from 2011-2015). Last follow-up was available until Dec 2016. Kaplan-Meier estimates were used to summarize the distributions of OS . Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between prior chosen factors (age, sex, race [Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic (H), Non-Hispanic Asian/Pacific Islander (NH A/P)], stage at diagnosis [I-II vs III-IV], marital status [married vs others], treatment-era [pre-novel agents vs novel agents era] and OS. Sensitivity analysis was explored to adjust the effect of follow-up duration difference between the two cohorts; patients who were in cohort 1 and whose follow-up duration was greater than the maximum follow-up duration of cohort 2 were considered censored at the time of the maximum follow-up duration of cohort 2 Results: There were total of 4957 patients analyzed in this study. In cohort 1 (pre-novel agent era) there were total of 2546 patients, n=1980 (78%) for NHWs, n=309 (12%) for Hs, n=166(7%) for NHBs, n=91(4%) for NH A/PIs; in cohort 2 (novel agent era), there were 2411 patients, n=1761(73%) for NHWs, n=371(15%) for Hs, n=176 (7%) for NHBs, n=103(4%) for NH A/PIs (p=.001) (Table 1). There was no difference in age at diagnosis, marital status, and sex between the two groups. Cohort 2 had more patients with Stage III-IV disease (55% in C2 vs 50% in C1, with p=.002) (Table 1). In the novel agent era, there were more patients who had chemotherapy "Yes" status compared to "No or Unknown" status (73% with "Yes" in Cohort 2 vs 68% with "Yes" in Cohort 1 with p&lt;.001) (Table 1). Cohort 1 had median follow-up of 8.33 years and Cohort 2 had median follow-up of 3.33 years. Cohort 1 had median OS of 4 years (3.58-4.25) years and Cohort 2 had median OS of 4.75 years (4.25-5.67) with HR of .92 (.85-1.00); p=.052 (Figure 1a). Hispanics had worse OS compared to NHWs with HR of 1.24 (1.09-1.40) with p &lt; .001; NHBs had similar OS compared to NHWs with HR of .95 (.79-1.13) with p&gt; .99 (Figure 1b). In the univariable analysis (UVA) to assess risk factors associated with OS, older age at diagnosis, Hispanic race, Stage III-IV and unmarried status were associated with worse OS. In the multivariable (MVA) analysis to assess risk factors associated with OS, older age at diagnosis, male gender, stage III-IV, unmarried status, Hispanic race and pre-novel agent era were associated with worse OS (Table 2). In the sensitivity analysis, HR was for OS was .92 (.85-1.00) with p=.039 for Cohort 2 (novel agent era) compared to Cohort 1 (pre-novel agent era). In the sensitivity analysis, the difference in OS between the NHWs and Hispanics remained; UVA and MVA for risk factors associated with OS remained the same after this adjustment also. CONCLUSION: In this SEER analysis, we found that elderly cHL patients who were diagnosed with cHL after novel agents such as brentuximab and CIs were approved (2011 and after) have improved survival by about 9 months compared to patients diagnosed before the approval of such agents (2006-2010). The improved survival likely reflects better efficacy and tolerability of these agents in elderly population as opposed to cytotoxic chemotherapy options. Lastly, we did not see any difference in survival of NHBs compared to NHWs unlike in previous SEER analysis; however, Hs still had worse OS compared to NHWs. In conclusion, OS of elderly cHL patients is improving in the novel agent era. Disclosures No relevant conflicts of interest to declare.

scholarly journals Is there a role for warfarin anymore?

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 541-546 ◽  
Author(s):  
Alan Jacobson
Keyword(s):  
Bleeding Risk ◽  
Novel Agents ◽  
The Novel ◽  
Management Options ◽  
Health Care Outcomes ◽  
Routine Clinical Setting ◽  
Hemorrhagic Risk ◽  
Care Outcomes ◽  
Effective Use

Abstract Reduction of atrial fibrillation–associated stroke risk has become the leading indication for warfarin use. Optimal management of warfarin can only be achieved with a relatively complex infrastructure. Alternative anticoagulant agents have been developed, and 3 have demonstrated effectiveness, safety, and adherence that are comparable or superior to warfarin in the clinical trial setting. None of the novel agents requires routine laboratory testing to demonstrate effective anticoagulation. Whereas these new agents present potential advantages, such as fixed dosing and dramatically reduced intracranial hemorrhaging, they are also subject to caveats that ought to be considered in the context of an “ideal” anticoagulant. If used casually, they have the potential to worsen rather than improve health care outcomes. There is little question that the management burden of the novel agents will be less than with warfarin. However, with a hemorrhagic risk that was similar to warfarin in these trials, there will likely remain a significant need for both baseline education and some level of focused interval follow-up to assess for bleeding risk and adherence considerations. These novel agents offer a definite advance in the available management options for thromboembolic disease, but until we understand the requirements for safe and effective use in the routine clinical setting, we will not be able to establish the extent to which they should replace warfarin.

Therapy of Acquired Aplastic Anemia (AA) with Rabbit Antithymocyte Globulin (rATG): A Retrospective Analysis by the Working Group on Non-Malignant Disorders of Hematopoiesis of the German Society of Hematology and Oncology (DGHO),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3434-3434
Author(s):  
Britta Höchsmann ◽  
Christiane Neher ◽  
Ulrich Germing ◽  
Janne Vehreschild ◽  
Juliane Eggermann ◽  
...  
Keyword(s):  
Data Collection ◽  
Aplastic Anemia ◽  
Research Funding ◽  
Response Rate ◽  
Retrospective Data ◽  
First Line ◽  
Off Label ◽  
Best Response ◽  
Retrospective Data Collection

Abstract Abstract 3434 Introduction: Several clinical trials established treatment with horse ATG (hATG) and cyclosporine A (CsA) as standard treatment of AA in patients (pts) who are not candidates for stem cell transplantation (SCT). In 2007 the hATG brand Lymphoglobulin® was withdrawn from the market. As the hATG brand ATGAM®, is not approved in Europe, hATG was replaced by rabbit ATG (rATG). Recently a large prospective randomized one-center study from NIH, USA comparing hATG ATGAM®/CsA and rATG Thymoglobulin®/CsA in untreated AA showed significantly lower response rates and survival with rATG. To obtain further information on rATG treatment in an unselected AA population, especially with a higher median of age and use of different rATG dosages we performed a retrospective data collection of first line rATG therapy on several centers. This shall reflect outcome after rATG in a real-world situation. Methods: Retrospective data collection and analysis of first line rATG treatment of AA after approval by Ethical Committee. Results: Up to now retrospective data of 64 pts from 18 centres in Germany were analysed. Characteristics of the pts: 30 male, 34 female; median age at time of therapy 54 years (6–80 years); 87.5% of pts had idiopathic AA. 51.6% of pts had severe AA, 32.8% very severe AA and 15.6% non-severe AA. Median granulocyte count was 0.3 G/l. 86% of the pts required red blood cell and 92% platelet transfusions. 56 of the evaluable pts received Thymoglobulin® and 5 pts Fresenius ATG S®. 52 of the 56 Thymoglobulin®-treated pts got this therapy in the years 2007–2011, i.e. not as deliberate primary choice of rATG but because hATG was no longer available. Median daily dose of Thymoglobulin® was 3.5 mg/kg (range from 2.5 – 3.75 mg/kg) for 5 days. 62 of 64 pts received additional immunosuppressive therapy with CsA and 19 of 64 pts received G-CSF. The median follow-up for surviving pts was 558.5 days (range, 78–3800 days). Response rates at time of best response of pts were CR in 10/58 pts (17%), PR in 18/58 pts (31%) and NR in 30/58 pts (52%) (only surviving patients with a minimum follow-up of 120 days were analyzed). Median interval to best response was 217 days. Response rate (PR+CR) was 16/33 (48.5%) in pts who received a Thymoglobulin® dose of > 3.5 –3.75 mg/kg/day versus only 4/14 (28.6%) group of 14 pts with a dose of > 2.5 to < 3.5 mg/kg/day (p=0.17; Fisher`s exact test). Relapses occurred in 3/28 responders and clonal evolution was observed in 3 pts (2 PNH, 1 MDS). Eighteen of 63 evaluable pts received allogenic SCT after ATG-therapy and were censored at the date of SCT. 23% of 44 pts without SCT died. In 6 of these 10 pts death was caused by infections. Other causes of death were bleeding, cardiac event, acute respiratory distress syndrome, adynamia. Overall probability of survival at 3 years was 75.8% (95% confidence interval (CI): 61.8 – 89.9%) and survival censored for SCT was 79.9% (CI: 66.0–92.8%). Survival was significantly better in responders (PR and CR) (94.1% at 3 years; CI: 82.9–100%) than in non-responders (58.0% at 3 years; CI 34.0 – 81.3%) (p=0.04; log-rank test). Adverse events were reported in 79.4% of 63 evaluable pts consisting of anaphylaxis/allergy in 27.3%, serum sickness in 12.7%, fever/chills in 34.5%, and bacterial/viral/fungal infections in 54.5% of pts. Conclusion: Response rate and survival after rATG+CsA in this retrospective analysis is lower than in historical controls (e.g. hATG+CsA treatment in previous controlled studies of the German AA Study Group and the EBMT AA Working Party; Frickhofen et al., Blood 2003; Tichelli et al., Blood 2011) and rate of (early) infections seem to be high. Our results are in accordance with recent reports from other groups. Additionally the results of this retrospective data analysis suggest a benefit for the patient group treated with a Thymoglobulin® dosage of > 3.5 –3.75 mg/kg/day compared to lower doses (< 3.5 mg/kg/day). There is growing evidence that best results in terms of response and survival are obtained by hATG-based immunosuppression. hATG can not be replaced by rATG without negative impact on patient outcome. There is need for action to achieve availability of hATG worldwide. If hATG is not available, treatment with rATG should be considered instead of no treatment or treatment with CsA alone since still about half of the patients respond to rATG. Disclosures: Höchsmann: Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Genzyme: Consultancy, Honoraria, Research Funding. Off Label Use: The use of the horse ATG ATGAM in Aplastic Anemia is off-label in Europe. At the moment no horse ATG with approval is available in Europe. Schrezenmeier:Genzyme: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Research Funding.

Long-Term Outcomes of Patients with Systemic Light Chain Amyloidosis (AL) Treated At Diagnosis with Risk-Adapted Stem Cell Transplant and Consolidation with Novel Agents.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3150-3150 ◽  
Author(s):  
Raymond L. Comenzo ◽  
Daniel E Fein ◽  
Hani Hassoun ◽  
Christina Bello ◽  
Joanne F Chou ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Initial Therapy ◽  
Novel Agents ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematologic Response

Abstract Abstract 3150 Background: AL is a plasma cell dyscrasia characterized by the pathologic production of monoclonal light chains which misfold, deposit in various organs, including the heart, and can cause early death. High dose melphalan with stem cell transplant (SCT) results in high hematologic response rates and is a standard treatment for eligible patients. Achieving a complete hematologic response (CR) to SCT results in extended event-free and overall survival (OS), up to 8 and 13 years respectively in one large series. (Blood 2011; 118:4346) We have studied the addition of novel agents as consolidation following risk-adapted SCT (RA-SCT) in order to improve hematologic response (HR) rates and therefore outcomes. (Br J Haem 2007;139:224; Amyloid 2010;17:80a) In this report we examine the long-term outcomes of patients who received initial therapy with RA-SCT followed by consolidation for hematologic response less than CR (HR < CR). Methods: We performed a retrospective study to assess the HR rates, incidence of hematologic progression and overall survival (OS) of AL patients enrolled at diagnosis on two consecutive phase II trials using RA-SCT with consolidation for HR < CR (NCT01527032 and NCT00458822). OS was calculated from date of transplant to date of death or last follow up. Median event free survival (EFS) and OS were estimated by the method of Kaplan Meier. Cumulative incidence function was used to estimate the incidence of progression and death. Results: Between 2002 and 2011, 83 patients were enrolled and underwent RA-SCT on these trials and, following RA-SCT, those with HR < CR received consolidation with thalidomide and dexamethasone (TD) in the first and bortezomib and dexamethasone (BD) in the second trial. Thirty-six patients had cardiac involvement (43%) and all patients had free light chain measurements employed to score hematologic response and progression using consensus criteria (Am J Hematol 2005;79:319; Blood 2010;116:1364a). The frequency of CR following SCT was 24% and increased to 48% with post-SCT consolidation. The CR rates increased at 1 year compared to 3 months post-SCT from 21% to 36% with TD and from 28% to 62% with BD. With a median follow up of 5.1 years, the EFS is 4.5 years (95% CI: 2.6 to not reached) and the OS of all patients has not been reached (Figure 1). Sixteen patients died prior to hematologic progression and 26 patients have progressed with a cumulative incidence of hematologic progression of 8%, 18%, and 29% at 1, 2 and 3 years, respectively (Figure 2). Thirty-one percent (8/26) of relapsed patients have not required second-line therapy while among those who have, 78% (14/18) have responded including 44% (8/18) with CR. The median OS following hematologic progression was 5 years (95% CI: 2.6–5.8). Conclusions: Half of the AL patients on initial therapy trials employing RA-SCT and consolidation for HR < CR achieved CR with 36% of pts on the TD and 62% on the BD consolidation trial in CR at 1 year post-SCT respectively. At 3 years post-SCT the cumulative incidence of relapse was 29% and a third of relapsed patients did not require therapy, likely due to the very sensitive serum free light chain assay that detects low level hematologic progression in the absence of organ progression. Almost 80% of patients requiring second-line therapy responded, over half with CR, and median OS after relapse was 5 years. These results indicate that initial therapy with RA-SCT and consolidation is an effective initial treatment strategy for patients with AL in the era of novel agents. With over 5 years of follow up the median OS has not been reached. Disclosures: Comenzo: Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Use of the investigational agent MLN9708, an oral proteasome inhibitor, in the treatment of relapsed or refractory light-chain amyloidosis. Hassoun:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Giralt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. Landau:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding.

Retrospective Analysis of Lymphomas in the Setting of Autoimmune Disease and the Impact of Immunosuppression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2737-2737
Author(s):  
Adam M. Petrich ◽  
Stefan Klaus Barta ◽  
Frederick Lansigan ◽  
Trent Wang ◽  
Ananta Bhatt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Retrospective Analysis ◽  
Clinical Features ◽  
Research Funding ◽  
Cytotoxic Chemotherapy ◽  
Prior Exposure ◽  
Primary Therapy ◽  
Histologic Subtype ◽  
The Impact

Abstract Introduction: Post-transplant lymphoproliferative disease (PTLD) encompasses a heterogeneous array of cases of lymphoma/lymphoma-like conditions arising in the setting of immunosuppression (IS) for prior organ or marrow transplant. Such pts face heightened risk of toxicity from exposure to cytotoxic chemotherapy, and may be best treated in the frontline with reduction of IS (RI) and anti-CD20 monoclonal antibody treatment (Trappe, 2012). Autoimmune (AI) disease has been associated with an increased risk of developing lymphoma; however, the relative impact of baseline clinical features, including prior IS, is unknown. Methods: We conducted a multicenter, retrospective analysis of adult pts with pre-existing AI conditions who were diagnosed with lymphoma since 1997. Baseline clinical features at diagnosis of lymphoid malignancy, including International Prognostic Index (IPI) risk factors; underlying AI disease; duration and type of IS; EBV status (by EBER in-situ hybridization); and primary therapy received (RI, rituximab [R] monotherapy, chemotherapy [+/- R]); were collected. Survival analyses were performed using Kaplan-Meier method. We then focused on those who had A) received IS other than corticosteroids (CS) alone; and B) those diagnosed with DLBCL. Those variables found to have significant correlation with OS by univariate analyses (UVA) were used to construct Cox proportional hazards model (multivariate analysis [MVA]) in order to determine which might have the strongest association with OS. Lastly, we sought to evaluate a potential role for RI and/or R as frontline therapy for those with DLBCL. Results: A total of 130 pts were included (Table 1). The most frequent AI disease was rheumatoid arthritis and for all cases, 76% had documented exposure to IS, for a median duration of 4.5 years (range 0.17-57 years) prior to diagnosis of lymphoma. The most common histologic subtype was DLBCL (52%). EBV status was reported for only 34% of pts, but was positive in 68% (25/37), all of whom had received prior exposure to IS beyond CS, and 80% of whom (20/25) were diagnosed with DLBCL. EBV status was infrequently tested in pts not previously exposed to IS (3/31). At a median follow-up of 61 months for the entire cohort, 2-year PFS and OS were 79% and 91%, respectively (Figure 1, Panel A). By UVA, age>60; PS>1; LDH> upper limit of normal (ULN); DLBCL (vs all other histologies); underlying rheumatoid arthritis (RA; vs all other AI diseases); and prior exposure to IS, each correlated with inferior OS (Table 1). By MVA, PS>1 and prior IS maintained significance (p<0.05). If those receiving only CS are grouped with those not previously exposed to IS, the correlation of this factor with OS was strengthened (p 0.008), and by MVA, PS>1 (p 0.002) and prior IS (p 0.010) maintain significance (data not shown). Among 67 pts with DLBCL, median age was 61 (range 26-90), 60% had advanced stage disease, and 32% had IPI of 4 or 5. At a median follow-up of 32 months, the 2-year PFS and OS were 82% and 84%, respectively. There were no differences in frequency of any IPI factors between patients exposed to prior IS (n=53) and those who were naïve to prior IS (n=14). For those not exposed to prior IS, the 2-year OS was 100%, compared to 80% in those who received prior IS (p 0.24); corresponding 2-year PFS were 92% and 79%, respectively (p 0.41). Age>60 and PS>1 were associated with an inferior OS but use of IS was not associated with outcome (Table 2). The 2 year OS for those treated with R plus CHOP(like) chemotherapy, CHOP(like) chemotherapy (without R), R alone (+/- RI), and with RI alone were 92%, 75%, 90%, and 67%, respectively (Figure 1, Panel B; log-rank p value 0.55). Patients who received CHOP-like therapy +/- R, as compared to R and/or RI were more likely to be naïve to IS therapy (15/46 vs 0/22, p = 0.003) and have 2 or more EN sites of disease (15/46 vs 2/22, =0.041). These differences notwithstanding, the 2-year PFS for the two groups were 86% and 74% (p 0.16), and 2-year OS for the two groups were 88% and 82%, respectively (Figure 1, Panel C; p 0.91). Conclusions: Pts with immunosuppression-related lymphoma have high rates of 2-year OS and in DLBCL, IS does not appear to be associated with an inferior outcome. Similar to evolving treatment paradigms in PTLD, rituximab monotherapy and other cytotoxic chemotherapy-free regimens as well as risk-adapted approaches may warrant further evaluation in IS-related DLBCL. Disclosures Petrich: Seattle Genetics: Consultancy, Honoraria, Research Funding. Barta:Seattle Genetics: Research Funding. Feldman:Celgene: Honoraria, Speakers Bureau; Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding.

Analysis of Transfusion Dependency Development and Disease Evolution in Patients with MDS with 5q- and without Transfusion Needs at Diagnosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3180-3180
Author(s):  
Felix Lopez-Cadenas ◽  
Blanca Xicoy ◽  
Silvia Rojas P ◽  
Kaivers Jennifer ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Research Funding ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Rank Test ◽  
Advisory Committees ◽  
Disease Evolution ◽  
Free Survival

Abstract Introduction: Myelodysplastic syndrome with del5q (MDSdel5q) is the only cytogenetically defined MDS category recognized by WHO in 2001, 2008 and 2016 and is defined as a MDS with deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow. It is known that for patients with MDSdel5q and transfusion dependence (TD), Len (LEN) is the first choice of treatment. However, data regarding factors that may impact on the development of TD or disease evolution in patients diagnosed without TD are scanty. In our study a retrospective multicenter analysis on patients with low-int 1 MDSdel5q without TD at diagnosis has been performed in order to answer these questions. Patients and methods: We performed a multicenter collaborative research from the Spanish (RESMD) and German MDS registries. Data from 153 low risk MDSdel5q without TD at diagnosis were retrospectively analyzed. Statistical analysis: Data were summarized using median, range, and percentage. The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (LEN or ESA). Transfusion or treatment free survival (TFS), overall survival (OS) and leukemia free survival (LFS) were measured from diagnosis to TD or treatment, the first occurred (or to last follow up if none), last follow up or death from any cause and evolution to AML, respectively. TFS, OS and LFS were analyzed using the Kaplan Ð Meier method. The Log-rank test was used to compare variables and their impact on survival for univariate analysis.Multivariate analysis was performed using Cox's proportional hazards regression model. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p<0.05. Statistical analysis was performed using SPSS 20.0. Results: Main clinical and biological characteristics were summarizing in table 1. From the total of 153 patients, finally 121 were evaluable. During the study 56 patients (46.2%) became in TD and 47 (38.8%) did not develop TD but received a modified disease course treatment. In this sense, most of the patients developed relevant anemia regarding those data (103 out of 121 patients, 85%). Median time to TD or treatment (TFS) was 20 months (1-132) from diagnosis. Secondary MDS (p=0.02), thrombocytosis (>350 109/L) (p=0.007), and neutropenia (<1.5 x 109/L) (p=0.02) were associated with poorer TFS. Thrombocytosis and neutropenia retained statistical significance in the multivariate analysis (Table 2). Among the TD patients (N=56), 42 (75%) received treatment: 28 LEN, 7 ESA and 7 other treatments. Among patients that did not develop TD (N=65), 47 (72.3%) received treatment before TD development: 16 LEN, 28 ESA and 3 other treatments. In order to know the evolution of these patients, survival analysis was performed. Median follow up was 58.9 months among alive patients and 57% of them were alive at the time of the last follow up. Estimated OS at 2 and 5 years was 94% and 64%. Regarding Univariate analysis, platelet <100 x 109/L (p=0.03), patients older than 71 years (p=0.001), and progression into AML (p=0.02) were associated with poorer OS. On the contrary, patients who had received treatment showed better OS (p<0.0001). This benefit is more evident among patients receiving LEN, median OS for patients receiving LEN, ESA/other treatments and not treated group was 137 months (CI 95%: 59,4 -215,5), 99,3 months (CI 95%: 46,6 -152) and 57,9 months (CI 95%: 38,2 -77,6), respectively, p<0.0001 (Figure 1). In the multivariate analysis, patients older than 71 years and LEN treatment retained the statistical significant impact on OS (Table 2). Twenty-eight patients (23%) progressed into AML, median time to AML was 35 months (5-122). When univariate analysis was performed, variables with adverse impact on LFS were platelets <100 x 109/L(p=0.019), neutropenia < 0.8 x 109/L (p=0.026), an additional cytogenetic abnormality (p=0.013) while treatment with LEN had a favorable impact (p=0.035). In the multivariate analysis only the presence of additional cytogenetic abnormalities retained statistical significance (Table 2). CONCLUSIONS: Most of the patients with low risk del(5q) MDS and no TD at diagnosis developed symptomatic anemia very early after diagnosis (20 months). Carefully monitoring should be stablished in order to detect this time point. Outcome of this subset of patients could improve after target therapy. Figure 1 Figure 1. Disclosures Del Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees. Díez Campelo:celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees.

Multiple myeloma in octogenarians: Clinical features and outcome in the novel agent era

2012 ◽  
Vol 89 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Efstathios Kastritis ◽  
Sossana Delimpasi ◽  
Eirini Katodritou ◽  
Eleftheria Hatzimichael ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
The Novel ◽  
Novel Agent

scholarly journals Promising Real World Survival Data in Adult-Onset Langerhans Cell Histiocytosis: An Australasian Lymphoma Alliance 20 Year Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2570-2570
Author(s):  
Georgia Mills ◽  
John Moore ◽  
Edward Cliff ◽  
Chun Yew Fong ◽  
Sarah Mangalasseril ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Research Funding ◽  
Progressive Disease ◽  
Treatment Strategies ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Adult Onset ◽  
Cns Involvement ◽  
Mutation Status

Abstract Background: Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm originating from bone marrow-derived CD207+/CD1+ clonal dendritic cells, with cells expressing BRAF V600E in around 50% of cases. Although more common in the paediatric setting, LCH is rare in adults, with an incidence of 1 to 2 cases per million. This combination of disease heterogeneity and infrequency means that data on treatment strategies and outcomes is limited, and a consensus on management is lacking. Data has historically been extrapolated from the larger paediatric cohort, with emerging phase II data on the efficacy and safety of upfront methotrexate and cytosine arabinoside (AraC) in adult LCH. Other agents used include cladribine (CdA), hydroxyurea, vinblastine, and prednisolone-based regimens, and more recently MEK/BRAF inhibitors, but none of these have been trialled prospectively. LCH can be an aggressive disease with a poor prognosis. Methods : We included patients aged ≥18 years diagnosed with LCH on histopathology between January 1, 2000 and August 1, 2021 from ten sites across Australia and New Zealand. Variables included demographic data, system and organ involvement, central nervous system (CNS) involvement, bone marrow involvement and BRAF V600E mutation status. Outcomes measured included overall survival (OS), progression-free survival (PFS) and total lines of therapy. Response to therapy was modified from the Scoring System of the HS LCH III trial: Complete response (CR) was defined by resolution of all signs of disease activity, including neuroendocrine dysfunction, skin and radiological lesions; and a partial response (PR) was defined as patients with "active disease better" and those with "mixed response". Stable or worsening symptoms/radiology were classified as progressive disease (PD). Patients who were alive or lost to follow-up were censored on the date of last follow-up. Results : We identified 46 patients with a median age at diagnosis of 39 years (range 18-81) (Table 1). The sex ratio was 1. 41% of patients had MS-LCH at diagnosis, of which 24% had high risk organ (liver, bone marrow, or spleen) involvement. 37% had multifocal bone disease. 28% of patients had CNS involvement at diagnosis. BRAF V600E mutation status was assessed in only 43% of cases, with a mutation frequency of 40%. The median number of lines of therapy was 1.7 (range 0-9). Three patients (7%) underwent lung transplantation for isolated pulmonary LCH. 31% percent of patients were treated with chemotherapy upfront, with the majority receiving AraC (43%,) and the remainder receiving vinblastine, prednisolone and 6-mercaptopurine (6-MP) (21%), vinblastine/prednisolone (21%), CdA (14%) or methotrexate and 6-MP (2%). Of note, 67% (n=4) of patients who were treated with upfront AraC and 100% (n=2) of patients treated with upfront CdA had a CR, while those patients treated with upfront vincristine-based regimes had, at best, a PR (50%, n=3) or PD (50%). Of the 46 patients, with a median follow up of 34.6 months (range 0.63-250.2), there were 7 deaths (15%) with 6/7 due to progressive disease, and the remaining death due to complications of lung transplantation. Median OS was not reached (Figure 1), while OS at 5 years was 85%. Median PFS was 9 years (range 0.05-21) (Figure 2), with a non-significant trend towards reduced PFS in patients with MS-LCH (5 years) compared to SS-LCH (9 years) (Figure 3). There was also a trend towards reduced OS in patients who received AraC as systemic therapy versus other forms of systemic therapy. Conclusion: We report the largest multicentre Australasian cohort of patients diagnosed with adult-onset LCH. OS and PFS were longer than previously reported in the literature. There remains significant heterogeneity in diagnostic and treatment strategies. There was a trend towards improved response rate to upfront AraC or CdA when compared to the vinblastine-based regimens, and further prospective research with these agents is required in this setting. Progress in this disease is challenging due its rarity, highlighting the need for standardisation of diagnostic and treatment strategies as well as a national and/or international registry. Figure 1 Figure 1. Disclosures Fong: Amgen: Research Funding; AbbVie, Amgen, Novartis, Pfizer, Astellas: Honoraria; Amgen, BMS: Speakers Bureau. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Cunningham: Principia Biopharma: Research Funding; Rigel: Research Funding; Janssen: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Amgen: Research Funding; Astex: Research Funding; Celgene: Research Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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