Risk-adapted therapy utilizing upfront brentuximab vedotin (Bv) and rituximab (R) with reduced toxicity chemotherapy in children, adolescents, and young adults with Hodgkin lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10532-10532
Author(s):  
Jessica Hochberg ◽  
Liana Klejmont ◽  
Lauren Harrison ◽  
Allyson Flower ◽  
Quihu Shi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Hodgkin Lymphoma ◽  
Combination Chemotherapy ◽  
Early Response ◽  
Brentuximab Vedotin ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Risk Patients

10532 Background: Cure rates for CAYA patients with Hodgkin Lymphoma remain high, however are limited by significant toxicity of chemoradiotherapy. Brentuximab Vedotin and Rituximab have shown efficacy in relapsed HL. We hypothesize that the addition of both to combination chemotherapy will be safe in newly diagnosed HL preserving current EFS with elimination of more toxic chemoradiotherapy. Objective: To evaluate the safety and overall response and EFS of Brentuximab and Rituximab in combination with risk adapted chemotherapy in CAYA with newly diagnosed HL. Methods: Age 1-30 yrs with newly diagnosed classical HL given 3 to 6 cycles of chemoimmunotherapy: Brentuximab vedotin with Doxorubicin, Vincristine, Prednisone and Darcarbazine (Bv-AVPD) for Low risk patients or Doxorubicin, Vinblastine, Darcarbazine and Rituximab (Bv-AVD-R) for Intermediate/High risk. Early response measured by PET/CT scan following 2 cycles. Slow responders received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk patients. Radiation therapy was given ONLY to those patients not in CR. Results: Total = 19 patients. Median age = 15yr (range 4-23yr). Risk = 2 low, 13 intermediate, 4 high. Toxcity = 1 episode of GrIII mucositis, 1 episode of GrIII infusion reaction to Brentuximab. 17 patients have completed therapy. All 17 patients achieved a complete response to therapy for a CR = 100%. Eleven (58%) have achieved a rapid early response. No patient has required radiation therapy. For 17 patients who have completed therapy, the EFS and OS is 100% with a median follow up time of 915 days (30 months). Conclusions: The addition of Brentuximab vedotin and Rituximab to combination chemotherapy for newly diagnosed Hodgkin Lymphoma appears to be safe. Our early results show significant promise with a CR rate of 100% and 58% rapid early response. We have successfully deleted toxic alkylator, topoisomerase inhibitor, bleomycin and radiation from this treatment regimen. The EFS/OS to date is 100% with a median follow up time of 2.5 years. Further follow up and a larger cohort is needed to determine long term outcomes of this approach. Clinical trial information: NCT02398240.

scholarly journals Reducing the Burden of Chemoradiotherapy with the Combination of Brentuximab Vedotin and Rituximab with Reduced Toxicity Chemotherapy in Children, Adolescents and Young Adults with Newly Diagnosed Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 127-127
Author(s):  
Jessica C. Hochberg ◽  
Jaclyn Basso ◽  
Liana Klejmont ◽  
Lauren Harrison ◽  
Allyson M. Flower ◽  
...  
Keyword(s):  
Young Adults ◽  
High Risk ◽  
Hodgkin Lymphoma ◽  
Early Response ◽  
Brentuximab Vedotin ◽  
Adolescents And Young Adults ◽  
Newly Diagnosed ◽  
Risk Patients ◽  
Stage Ia

Background: Cure rates for newly diagnosed Hodgkin Lymphoma remain high through the combined use of chemoradiotherapy. (Hochberg/Cairo Cancer Journal 2018) However, this has resulted in significant adverse physical and psychosocial function that significantly impacts the quality of life among survivors, including cardiotoxicity, neurocognitive deficits, poor quality of life, and secondary malignancies. Pediatric cancer survivor studies have shown significant increases adverse health events following therapy throughout adulthood. Major risk factors for late effects include significant exposure to radiation, anthracyclines, cyclophosphamide, etoposide and bleomycin. (Bhakta et al Lancet 2017, Oeffinger et al NEJM 2006, Gibson et al Lancet Oncol 2018) Immunotherapy targeting the Reed Sternberg cell and tumor microenvironment, including regulatory B-cells, has potential to reduce the burden of traditional treatment. Brentuximab Vedotin, an anti-CD30 antibody-drug conjugate, and Rituximab, a chimeric anti-CD20 monoclonal antibody, have both shown efficacy in relapsed Hodgkin Lymphoma and Brentuximab has gained FDA approval in up front adult HL in combination with standard chemotherapy. (Younes et al JCO 2012, Younes et al Blood 2012, Connors et al NEJM 2018) We hypothesized that the addition of Brentuximab vedotin (Bv) and Rituximab (R) combined with risk adapted chemotherapy will be well tolerated and effective in children, adolescents and young adults with all stages of newly diagnosed Hodgkin lymphoma and will allow for the elimination of more toxic chemotherapies as well as need for radiation. Objectives: To evaluate the safety, tolerability and overall response rate of Brentuximab vedotin and Rituximab in combination with risk adapted chemotherapy in children, adolescents and young adults with newly diagnosed Hodgkin Lymphoma. Methods: Eligible patients 1-30 yrs with all stages of newly diagnosed classical Hodgkin Lymphoma. Patients were risk assigned as either Low (Stage IA, IIA, no bulk), Intermediate (Stage IA bulk/E, IB, IIA bulk, IIB or IIIA) and High Risk (Stage IB bulk/E, II bulk, IIIA bulk, IIIB, IV). Low risk patients were given 3 cycles of Brentuximab vedotin (1.2mg/kg) with Doxorubicin (25mg/m2), Vincristine (1.5mg/m2), Prednisone and Dacarbazine (375mg/m2) on Days 1 and 15. Intermediate and High Risk patients received 4 or 6 cycles of Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine and Rituximab (375mg/m2) on Days 1,2 and 15, 16. (Figure 1) Early response was measured by PET/CT scan. Slow responders, defined by lack of a complete metabolic response or <80% size reduction, received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk. Involved Field RT was restricted to only patients with bulk disease with SER and those not in a CR at the end of therapy. Humoral and cellular immunity was measured upon completion of therapy. Results: Total enrolled = 33 patients. Median age = 15yr (range 4-23yr). Total 12 males, 21 females. Risk Assignment = 4 low, 17 intermediate, 12 high. Toxicity = 1 episode of Gr III mucositis, 1 episode of Gr III infusion reaction to Brentuximab vedotin, 2 episode Gr III peripheral neuropathy. All 33 patients achieved a complete response for a CR = 100%. Eighteen patients (58%) achieved a rapid early response. Four patients (only 12%) have required radiation therapy to date due to the presentation of bulky disease with a slow early response. Each of these patients was in CR prior to the start of radiation therapy. At a median follow-up of 18 months, the mean±SEM IgG level, CD19 and CD3 levels were 1097±63, 325±105, and 1273±290, respectively, all within normal range. Furthermore, none of the patients developed agammaglobulinemia or required hospitalization for systemic infection during or following treatment. The EFS and OS is 100% with a mean follow up time of 1320 days (= 44 months, range 3-80). (Figure 2) Conclusions: The addition of Brentuximab vedotin and Rituximab to combination risk adapted chemotherapy (without cyclophosphamide, etoposide or bleomycin) for newly diagnosed Hodgkin Lymphoma appears to be safe in children, adolescents and young adults. Our results show significant promise with a CR rate of 100%, 58% rapid early response and significant reduction in the use of toxic chemotherapy and radiation. The EFS/OS to date is 100% with a median follow up time of greater than 3.5 years. Disclosures Cairo: Osuka: Research Funding; Miltenyi: Other: MTA; Jazz Pharmaceuticals: Other: Advisory Board, Research Funding, Speakers Bureau.

scholarly journals Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care—a cohort study

2019 ◽  
Vol 30 (3) ◽  
pp. 402-407
Author(s):  
Daphne M Stol ◽  
Monika Hollander ◽  
Ilse F Badenbroek ◽  
Mark M J Nielen ◽  
François G Schellevis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Cohort Study ◽  
High Risk ◽  
Newly Diagnosed ◽  
Additional Risk ◽  
High Risk Patients ◽  
Detection Program ◽  
Risk Patients

Abstract Background Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline ‘the prevention consultation’ provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. Methods A cohort study among 30 934 patients, aged 45–70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. Results Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. Conclusions Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors—such as elevated glucose, blood pressure and cholesterol levels—found, requiring active follow-up and presumably treatment in the future.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 292-292 ◽  
Author(s):  
Joseph M Connors ◽  
Stephen Ansell ◽  
Steven I. Park ◽  
Michelle A. Fanale ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Rate ◽  
Phase 1 ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Genetics Research

Background: The ABVD regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine is a common standard of care for the frontline treatment of advanced stage Hodgkin lymphoma (Santoro 1987; Duggan 2003) and is curative for the majority of patients; however, up to 30% of patients require a secondary therapy. Hodgkin Reed-Sternberg cells of classical HL (cHL) typically express CD30. In a pivotal phase 2 trial brentuximab vedotin (A, ADCETRIS®), comprised of an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) induced an objective response rate (ORR) of 75% and complete response rate (CR) of 34% in highly treatment-refractory patients with cHL (Younes 2012). Methods: We conducted a phase 1, open-label, multicenter study to evaluate the safety and efficacy of A when administered in combination with standard therapy (ABVD) or the same regimen without bleomycin (AVD) (Younes 2013). Adult patients with newly diagnosed advanced stage (II bulky, II B, III or IV; 80% stage III or IV) received doses of 0.6, 0.9, or 1.2 mg/kg A with standard doses of ABVD or 1.2 mg/kg with AVD, depending on cohort assignment on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Previously we reported that among patients assessable for response 95% of patients given ABVD+A achieved a CR, as did 96% of patients given AVD+A. None of 26 patients given AVD+A but 11 of 25 (44%) given ABVD+A experienced pulmonary toxicity, including 2 deaths, establishing that A cannot be safely combined with bleomycin. In this current study we provide the long term survival and safety data on patients enrolled in the phase 1 trial. Results: In total 51 patients were assigned to either ABVD+A (n=25) or AVD+A (n=26). 1 patient who withdrew from the trial during the first cycle of ABVD+A is excluded from this analysis and 1 patient who received 3 cycles of ABVD+A, then withdrew, then received 3 cycles of ABVD alone and 2 patients who died during treatment (pulmonary toxicity) are included (total n=50). Median follow-up from diagnosis for the 24 patients treated with ABVD+A is 41 months (range 9-51 months) and for the 26 patients treated with AVD+A, 31 months (range 9-35 months). All 26 patients treated with AVD+A have been followed longer than the longest time to relapse (7 months). 45 patients remain in first CR and 5 treatment failures have occurred: 4 in the ABVD+A cohort (2 toxic deaths; 2 relapses (9 and 23 months from diagnosis)) and 1 after AVD+A (7 months from diagnosis). 3y-failure-free survival (3y-FFS) is 83% and 96% for ABVD+A and AVD+A, respectively, and 3y-overall survival (3y-OS), is 92% and 100%. No additional toxic deaths have occurred in follow-up. Conclusions: These updated outcomes reflecting the impact of adding brentuximab vedotin (1.2 mg/kg) to standard doses of AVD for classical Hodgkin lymphoma, demonstrating 96% 3y-FFS and 100% 3y-OS with no major unexpected toxicity, strongly support the current large international trial comparing AVD-A (AVD+1.2mg/kg brentuximab vedotin) to standard ABVD (ECHELON-1, clinicaltrials.gov NCT01712490), which may identify a new, less toxic gold standard treatment for advanced stage classical Hodgkin lymphoma. Disclosures Connors: Seattle Genetics: Research Funding. Off Label Use: brentuximab vedotin in phase 1 trial. Ansell:Seattle Genetics: Research Funding. Park:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding. Fanale:Seattle Genetics: Research Funding. Younes:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding.

Characteristics and Treatment Response of Newly Diagnosed Advanced-Stage and Relapsed/Refractory Hodgkin Lymphoma in Taiwan: A Nationwide Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Chieh-Lin Jerry Teng ◽  
Tran-Der Tan ◽  
Yu-Wen Lin ◽  
Pei-Wen Lien ◽  
Hsin-Chun Chou ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Outcomes ◽  
Clinical Features ◽  
Advanced Stage ◽  
Stage At Diagnosis ◽  
Newly Diagnosed ◽  
First Line ◽  
Stage Disease ◽  
Risk Patients

Background Hodgkin lymphoma (HL) is a highly curable hematological neoplasm, even in an advanced stage. However, despite improvements in treatment, patients with primary refractory and/or relapsed HL (RRHL) still have a poor prognosis. Because of relatively low incidence, studies focusing on the clinical characteristics or outcomes for patients with advanced-stage HL and RRHL in Asia are few. The present study aimed to describe the clinical features and survival of these patients in Taiwan using a nationwide database. Methods This retrospective descriptive study was conducted by using the Taiwan Cancer Registry and the National Health Insurance Research Database. All newly diagnosed HL patients who started frontline treatment with an intent to cure were enrolled from 2009 to 2016. Patients who had an advanced-stage disease (i.e., stage III/IV) at diagnosis were identified. All chemotherapy agents prescribed during the 60-day period after the date of first treatment were considered as the same line regimen. Patients with RRHL were identified as those receiving a new chemotherapy for HL (across stages) other than the first-line regimen or undergoing an autologous stem cell transplantation (ASCT) at any time. We described the first-line regimens for newly diagnosed advanced-stage HL and salvage therapy for RRHL. Characteristics and survival outcomes, including overall survival (OS) and time to next treatment (TTNT, as a surrogate for progression-free survival, PFS), were further analyzed for patients who received ABVD or ABVD-like (BVD and AVD) regimen as the first-line treatment, specifically in those with advanced stage at diagnosis and RRHL patients who received ASCT. Results Between 2009 and 2016, 1,156 newly diagnosed HL patients with an intent-to-cure treatment were enrolled; of whom 490 were advanced stage at diagnosis. A bimodal age distribution with peaks around 20-44 and after 65 years was observed. Among the patients with an advanced stage disease, ABVD was the dominant frontline regimen, accounting for 79% of treated HL cases, followed by ABVD-like regimens (15%), and BEACOPP (3%). The median age of patients receiving ABVD/ABVD-like regimen was 34 years, and 62% were male. Over half of the patients were stage IV (57%), having extra-nodal disease (58%), and/or B-symptoms (54%). Only 19% of them received radiotherapy along with chemotherapy. With a median follow-up of 4.7 years, the OS and PFS rates were 76% and 52%, respectively. Among 321 RRHL patients, 288 had received ABVD/ABVD-like regimens as frontline therapy. In this 288-patient cohort, 135 (47%) proceeded to ASCT. Among these 135 patients, ESHAP was the commonest salvage therapy (62%), followed by ICE (15%), and others (7%). After a 3.9-year median follow-up, the OS and PFS rates were 76% and 47%, respectively. Discussion The current study describes the clinical characteristics and treatment outcomes of patients with advanced-stage HL and RRHL in Taiwan. Prior studies describing clinical features and outcomes of HL patients in Taiwan are limited to a single medical center experience. Our study provides nationwide data and suggests the clinical features of advanced-stage HL patients are not much different from those in Western countries. Though the OS of advanced-stage HL remained high, half of the patients who received standard treatment developed relapsed/refractory disease, suggesting a strong unmet need for better novel therapies. Among the RRHL patients receiving ASCT, about half of them experienced further disease progression, and a quarter died afterwards. This observation highlights the importance of identifying high-risk patients for progression. Moreover, regimens that include novel agents may improve the outcomes of early high-risk patients. Further studies are needed to determine the real-world treatment outcomes and cost-effectiveness of these novel agents. Conclusion The characteristics of advanced-stage HL in Taiwan were comparable to those in Western countries. Considering the poor prognosis of RRHL, it is crucial to identify patients with a high risk of progression in the first line so that we can optimize their treatment outcomes. Disclosures Lien: Takeda Pharmaceuticals Taiwan: Ended employment in the past 24 months. Chou:Takeda Pharmaceuticals Taiwan: Current Employment. Lin:Takeda Pharmaceuticals Taiwan: Research Funding.

Factors contributing to delayed diagnosis in nasopharyngeal carcinoma

1999 ◽  
Vol 113 (7) ◽  
pp. 633-636 ◽  
Author(s):  
Jern-Lin Leong ◽  
Kam-Weng Fong ◽  
Wong-Kein Low
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Delayed Diagnosis ◽  
Atypical Presentation ◽  
Newly Diagnosed ◽  
Therapeutic Radiology ◽  
Singapore General Hospital ◽  
Risk Patients

AbstractNasopharyngeal carcinoma (NPC) can be difficult to diagnose. Not only is the post-nasal space (PNS) inaccessible to examination, it is frequently occupied by normal lympho-epithelium which can make differentiation from NPC difficult. Together with its frequent atypical presentation, it is not surprising that the diagnosis is missed or delayed. This is undesirable as the treatment of early NPC carries an excellent prognosis. The aim of this study is to ascertain the extent of the problem of missed or delayed diagnosis and to study the factors responsible.This was a retrospective study of all newly diagnosed patients with NPC from the Singapore General Hospital and treated in the Department of Therapeutic Radiology in the year 1996 (1 January-31 December).A total of 126 patients were studied. Eighteen patients (14.3 per cent) were found to have delayed diagnosis of more than a month. The delay ranged from 1.2 to 25 months (mean 7.2 months). Factors identified which contributed to delayed diagnosis included i) Clinicians not considering a diagnosis of NPC ii) Clinicians suspecting NPC but misled by the results of investigations iii) Patients refusing investigation or defaulting follow-up.Nearly a fifth of patients with NPC had delayed diagnosis. Many of the factors responsible for the delays appear to be preventable by better patient education and counselling, doctors having sharper clinical acument and skills in NPC diagnosis and the hospital administration having a system of tracking down high risk patients who default.

scholarly journals Long-Term Follow-Up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma

2020 ◽  
Vol 38 (17) ◽  
pp. 1928-1937 ◽  
Author(s):  
Nisha S. Joseph ◽  
Jonathan L. Kaufman ◽  
Madhav V. Dhodapkar ◽  
Craig C. Hofmeister ◽  
Dhwani K. Almaula ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Therapy ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Entire Cohort ◽  
Induction Regimen ◽  
Risk Patients ◽  
Standard Risk

PURPOSE The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a highly effective and convenient induction regimen for both transplantation-eligible and -ineligible patients with myeloma. Here, we present the largest cohort of patients consecutively treated with RVD induction therapy followed by risk-adapted maintenance therapy with the longest follow-up and important information on long-term outcomes. PATIENTS AND METHODS We describe 1,000 consecutive patients with newly diagnosed myeloma treated with RVD induction therapy from January 2007 until August 2016. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board–approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. RESULTS The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively. CONCLUSION RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes. This study includes the largest cohort of patients treated with RVD reported to date with long follow-up and demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.

scholarly journals Firstline Daratumumab Shows High Hematologic and Organ Response Rates in Advanced Cardiac AL Amyloidosis - a Retrospective Case Series

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3123-3123
Author(s):  
Georg Jeryczynski ◽  
Antonia Eder ◽  
Eva-Maria Reitter ◽  
Maria-Theresa Krauth ◽  
Hermine Agis
Keyword(s):  
High Risk ◽  
Median Time ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Stage Iiia ◽  
Hematologic Response ◽  
Risk Patients ◽  
Organ Response ◽  
Very High

Background AL amyloidosis is a plasma cell dyscrasia and the most common form of amyloidosis. It is associated with deposition of light chain amyloid, which leads to organ dysfunction, most commonly of the heart and kidneys. Treatment focuses on the reduction of the production of the monoclonal light chains and includes the off-label use of antimyeloma drugs. Their use, however, is often limited by the advanced organ dysfunction frequently encountered in these patients. Daratumumab, a monoclonal CD38 antibody has shown efficacy in both newly diagnosed and relapsed AL amyloidosis in several reports. It is usually well tolerated in patients with advanced AL amyloidosis-related heart failure and requires no dose adjustment for impaired kidney function. Aims and Methods The aim of this study was to retrospectively assess the efficacy of daratumumab in a single-center cohort of newly diagnosed AL amyloidosis patients. A chart review was performed on all patients treated with frontline daratumumab as an individual healing attempt at the Department of Oncology at the Medical University of Vienna between April 2017 and May 2019. Results A total of 14 patients (nine male, five female) were evaluable. According to the 2004 Mayo staging system one patient was stage I, four patients were stage II and nine patients were stage III, two of which were in the very high risk group IIIb (NT-proBNP > 8500 ng/L). Twelve patients produced monoclonal lambda light chains. Median number of organs involved was 2 (1-4), with heart (78.6%) and kidneys (64.3%) being the most common. All patients received daratumumab at the dose of 16 mg/m2 for at least 3 cycles (range 3-19). Dexamethasone was reduced to 20 mg per daratumumab infusion to increase tolerability. After a median follow-up of 12.5 months (range 2.17-25.17), eleven patients were still receiving daratumumab at time of analysis. One patient with stage IIIa proceeded to heart transplant after four cycles and later underwent autologous stem cell transplantation, while two patients were lost to follow-up (one patient had to withdraw from treatment due to psychiatric comorbidities; one patient moved to a different center). Seven patients were treated with daratumumab alone, seven patients received either additional proteasome inhibitors, additional IMIDs, or both during the course of their treatment. One patient was also briefly treated with oral cyclophosphamide. Two patients experienced infusion reaction at first administration. There was no severe toxicity leading to discontinuation observed, the most significant toxicity was susceptibility to infections for which six patients received intravenous immunoglobulins. Hematologic and organ response were assessed using previously published criteria (Comenzo et al 2012). All patients showed hematologic response at last follow-up. First hematologic response was classified as PR in 50% and VGPR in 50% after a median time of 44 days (7-252). Best hematologic response was VGPR in 78.6% and CR in 21.4%. The rates remained the same to last follow-up. Median time to best response was 277 days (14-412). In the group of high and very high risk patients 77.8% achieved VGPR and two stage IIIa patients (22.2%) achieved CR at last follow-up. Cardiac response was seen in five out of eleven evaluable patients, all classified as stage IIIa, while kidney response was seen in three out of nine (33.3%) patients with kidney involvement. Median time to heart and kidney response was 281 (88-348) and 196 (62-215) days respectively. Conclusion Daratumumab showed high efficacy as a firstline treatment in newly diagnosed AL amyloidosis yielding a 100% objective hematologic response rate and a significant organ response rate even in high risk patients that usually have a very poor prognosis and limited treatment options. Despite the limitations inherent to any retrospective study, our data underline the role of daratumumab as a safe, effective, and tolerable treatment option in AL amyloidosis both as a monotherapy as well as a combination partner for other agents, in particular in patients with advanced stage AL amyloidosis. Figure OffLabel Disclosure: Off-label use of daratumumab in AL Amyloidosis as an individual healing attempt

For Standard and High-Risk Patients with Hodgkin Lymphoma Six Cycles of Tailored BEACOPP, Based On Interim Scintigraphy, Are Effective and Female Fertility Is Preserved.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1552-1552 ◽  
Author(s):  
Eldad Dann ◽  
Rachel Bar-Shalom ◽  
Ada Tamir ◽  
Menachem Ben-Shachar ◽  
Irit Avivi ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Young Female ◽  
Prognostic Features ◽  
High Risk Patients ◽  
Female Patients ◽  
Interim Pet ◽  
Pet Ct ◽  
Risk Patients

Abstract Abstract 1552 Poster Board I-575 This prospective study (124 patients) evaluated the outcome of patients with Hodgkin lymphoma (HL) whose therapy was tailored based on results of scans performed after 2 cycles of chemotherapy, thus reducing the dose for early responders and maximizing the dose for those with subptimal early response or progression. The study was initiated in 1999 for patients with HL aged 18-60 years. Eligibility criteria were: unfavorable HL stages I, II and stage III or IV. Disease was defined according to the International Prognostic Score (IPS). Standard risk patients were treated with 2 cycles of standard BEACOPP (SB) and those with IPS of 3 3 got 2 cycles of escalated BEACOPP (EB): Ga67(on 57 patients prior to 2001) or hybrid PET/CT scan (on all 67 since 2001) were performed at diagnosis and after the 1st or 2nd cycle for all 124 patients. If early interim scan remained positive, additional 4 cycles of EB were used; otherwise, SB was given. Data for 108 patients were previously reported (Blood, 2007); albeit with a median follow-up of only 4 years. Herein is an updated 6- year median follow-up for all previously reported patients who had Ga67 or PET/CT as well as 16 additional patients who underwent interim PET/CT. Furthermore, importantly, the fertility of all young female patients is herein reported. For all 124 patients on study, the 7-year event-free survival (EFS) for patients with IPS 0-2 is 89% and for those with IPS of 3 3 87%. Seven year overall survival (OS) is 90%. Sixty seven patients (39 males and 28 females aged 18-55 [median 33]) were treated after 2001 when hybrid FDG-PET/CT became available. Forty one patients had IPS of 0-2 and 26 ≥3. Complete remission (CR) rate was 96%, 5-y FFS and OS were 92% and 97%, respectively at a median follow-up of 56 months (8-90). 5-y EFS and OS were similar for standard and high risk patients. HL progressed in 2/12 patients with interim positive PET/CT versus 3/55 with negative PET (p<0.02) (Table 1). Ninety four percent of patients with negative interim PET/CT had no disease progression during the follow-up, while 17% of patients with interim positive PET/CT progressed. One patient died from breast cancer. Thirty-eight females < 40 years old who had been treated with tailored BEACOPP since 1998 were assessed for fertility status. This is described in Table 2. Twenty six were co-treated with the GnRH agonist triptorelin, concomitantly with chemotherapy. Nineteen conceived during follow-up. Thirteen delivered 17 healthy babies, 6 terminated their pregnancy. Conclusion PET/CT is useful for making an early interim decision about chemotherapy dose on an individual basis, thus reducing unnecessary toxicity and escalating therapy where appropriate based on poor interim prognostic features. The results of 6 cycles of risk-adapted BEACOPP compare favorably with the reported data following 8 cycles of EB. Use of tailored therapy enables reduction of cumulative chemotherapy and preservation of fertility in the majority of young female patients. Disclosures Rowe: Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.

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