Nivolumab and brentuximab vedotin (BV)-based, response‐adapted treatment in children, adolescents, and young adults (CAYA) with standard-risk relapsed/refractory classical Hodgkin lymphoma (R/R cHL): Primary analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8013-8013
Author(s):  
Peter D. Cole ◽  
Christine Mauz-Körholz ◽  
Maurizio Mascarin ◽  
Gérard Michel ◽  
Stacy Cooper ◽  
...  
Keyword(s):  
Metabolic Response ◽  
High Dose Chemotherapy ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Primary Analysis ◽  
Immune Mediated ◽  
Phase 2 Study ◽  
Report Data ◽  
Standard Risk

8013 Background: Outcomes for younger patients (pts) with R/R cHL are poor, particularly for those without complete metabolic response (CMR) before autologous transplant (auto-HCT). Nivolumab + BV has shown 67% CMR and a high 2-y PFS rate as first salvage in adults with R/R cHL. CheckMate 744 (NCT02927769) is an ongoing phase 2 study for CAYA with R/R cHL, evaluating a risk-stratified, response-adapted approach using nivolumab + BV and, for pts without CMR, BV + bendamustine. In the initial analysis of the standard-risk cohort (R2), the regimen was well tolerated with high CMR rates before consolidation with high-dose chemotherapy plus auto-HCT. We report data from the primary analysis. Methods: Pts were aged 5–30 y and had first-line treatment (tx) without auto-HCT. Risk stratification has been described previously (Harker-Murray, ASH 2018). Pts received 4 induction cycles of nivolumab + BV; pts without CMR by blinded independent central review (BICR) received BV + bendamustine intensification. Pts with CMR at any time could proceed to consolidation off study. Response was per Lugano 2014 criteria. Primary endpoint: CMR rate (Deauville ≤3) per BICR any time before consolidation. Results: At database lock, 44 pts were treated in R2 (median follow up: 20.9 mo); 43 received 4 induction cycles and 11 received intensification. Median age was 16 y (range 9–30); 24 (55%) pts had primary refractory cHL and 20 had relapsed cHL. CMR rates and ORR any time before consolidation and after induction are shown in Table. 1-y PFS rate by BICR was 91% (90% CI 77–96). During induction, 8 (18%) pts experienced grade (G) 3–4 tx-related adverse events (TRAEs); the most common any grade TRAEs were nausea and hypersensitivity (20% each). 1 TRAE led to discontinuation (G3 anaphylaxis). Most tx-related immune-mediated AEs were G1–2 (1 pt had 2 G3 infusion-related reactions). Conclusions: This risk-stratified, response-adapted approach offers a well-tolerated salvage strategy with high CMR rates and no new safety signals for CAYA with R/R cHL. Most pts avoided alkylator exposure prior to consolidation. Further follow up may confirm durability of disease control. Clinical trial information: NCT02927769 . [Table: see text]

scholarly journals SEOM clinical guideline for management of adult medulloblastoma (2020)

2021 ◽  
Author(s):  
R. Luque ◽  
M. Benavides ◽  
S. del Barco ◽  
L. Egaña ◽  
J. García-Gómez ◽  
...  
Keyword(s):  
Residual Tumor ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Molecular Alterations ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Risk Patients ◽  
Standard Risk

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

scholarly journals Prolonged Overall Survival (OS) in a Subset of Responders to the Combination of Brentuximab Vedotin (Bv) and Bendamustine (B) in Heavily Treated Patients with Relapsed or Refractory Hodgkin Lymphoma (HL): Results of an International Multi- Center Phase I/II Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2907-2907 ◽  
Author(s):  
Ahmed Sawas ◽  
John Kuruvilla ◽  
Jennifer Kimberly Lue ◽  
Changchun Deng ◽  
Jennifer E Amengual ◽  
...  
Keyword(s):  
Research Funding ◽  
Response Rate ◽  
Phase 1 ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Refractory Hodgkin Lymphoma

Abstract Introduction Prognosis for patients who fail to respond to high-dose chemotherapy or progress after high dose chemotherapy and autologous stem cell transplant (ASCT) is particularly poor, with a recent study reporting 71% of patients dying in year 1 and 90% by year 2, with a median -progression survival of 1.3 years [1]. In our study of brentuximab vedotin plus bendamustine (BvB) in patients with relapsed or refractory Hodgkin's lymphoma, we recently reported an overall response rate (ORR) and complete response rate (CR) of 71% and a 32% respectively (N=65) in a heavily treated patient population [2]. Having noted several patients with a progression free survival (PFS) of 1 year or longer, we reviewed all enrolled patients for protracted duration of benefit, raising the question as to whether these patients may have been cured by BvB in the salvage setting. (ClinicalTrials.gov #NCT01657331). Methods Among 65 enrolled patients we identified 23 with a PFS of more than one year after treatment with BvB. Patients had received Bv on Day 1 with B on Days 1 and 2 of a 3-week cycle for up to 6 cycles. In the Phase 1 study 4 dose levels were evaluated: (1) Bv = 1.2mg/kg; B = 70mg/m2; (2) Bv = 1.2mg/kg; B = 80mg/m2; (3) Bv = 1.8mg/kg; B = 80mg/m2; and (4) Bv = 1.8mg/kg; B = 90. Accrual followed a classic Fibonacci dose escalation, with 3 patients being treated at each dose level. Dose Limiting Toxicity (DLT), defined as any CTC version 4 Grade 3 or 4 toxicity led to expansion of the dose cohort. The recommended phase II dose was Bv 1.8 mg/kg on Day 1 and B 90 mg/m2 on Days 1 and 2. The Phase 2 portion of the study accrued an additional 37 patients. Response was assessed by the investigator per Cheson 2007 after cycles 2 and 6. Patients were followed post completion of therapy every 3 month until disease progression and imaging was conducted every 3- 6 months. Study procedures and follow-up were concluded on June 30th 2018. In addition, plasma and serum biomarkers were prospectively collected for correlation with toxicity and response. Results With a median follow-up of 33 months (range 20-58 month) we identified 23/65 patients (43% male) with a median age of 34 years (range, 18-55) who experienced a PFS of 1 year or more. The median number of prior systemic therapies was 3 (range 1-6); with 11 patients having had prior ASCT and 10 patients receiving prior radiation therapy. Median number of BvB cycles administered was 4 (range 2-6). A best response of CR was documented for 17 patients (74%) and partial response (PR) was documented for 6 patients (26%). Consolidation with HDCT-ASCT was performed in 10 patients, 3 of whom received maintenance Bv post-transplant. The median duration of response (DOR), PFS and OS among this group was 28, 32 and 34 months, respectively. All responses are ongoing with no evidence of relapse. Long term survival with no further therapy after a median of 6 cycles of BvB ( range 2-6) was observed in 13 patients (20% of the treated population) (median post-BvB PFS 36 months, range 20-58). Exploratory analysis of the correlation between disease outcome and changes from baseline in select biomarkers demonstrated a significantly lower mean baseline sCD30 level among long term responders (p=0.01). No correlations were noted between other clinical outcome metrics and sCD30, nor with other biomarkers including TARC, CD163, or galectin. Conclusion In this heavily treated population with HL, the combination of BvB represents an effective and tolerable outpatient salvage regimen with long term response and protracted survival among a subset of patients, and raises the prospect that these patients, with a historically poor outcome may be cured with BvB. We intend to follow these patients to obtain additional information on their longer term outcome. ReferencesZagadailov, E.A., et al., Real-world effectiveness of brentuximab vedotin versus physicians' choice chemotherapy in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplantation in the United Kingdom and Germany. Leuk Lymphoma, 2018. 59(6): p. 1413-1419.O'Connor, O.A., et al., Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet Oncol, 2018. 19(2): p. 257-266. Disclosures Kuruvilla: Princess Margaret Cancer Foundation: Research Funding; Merck: Consultancy, Honoraria; Leukemia and Lymphoma Society Canada: Research Funding; Lundbeck: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria. O'Connor:ADC Therapeutics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding.

Risk Adapted BEACOPP Regimen Based on Early Scintigraphy Can Reduce the Cumulative Dose of Chemotherapy for Standard and High Risk Hodgkin Lymphoma (HD) with No Impairment of Outcome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 815-815
Author(s):  
Eldad J. Dann ◽  
Rachel Bar Shalom ◽  
Nissim Haim ◽  
Ada Tamir ◽  
Menachem Ben Shachar ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose Chemotherapy ◽  
Stage I ◽  
Stage Iii ◽  
High Dose ◽  
Eligibility Criteria ◽  
Risk Patients ◽  
A Prospective Study ◽  
Standard Risk

Abstract A prospective study evaluating the outcome of HD pts whose chemotherapy was tailored based on results of scans performed after 1or 2 cycles of chemotherapy reducing the cumulative chemotherapy for early responders and maximizing the dose for late responders. Study was initiated in 1999 for patients with classical HD age 18–65y. Eligibility criteria were either stage I, II with unfavorable features (see table) or any stage III or IV HD. Those with I-II B or bulky or any Stage III-IV were defined according to IPS. Patients with standard risk were treated with 2 cycles of standard BEACOPP (SB). Those with high risk were treated with 2 cycles of escalated BEACOPP (EB). GA67 or FDG PET scan was performed at diagnosis and after the 1st or 2nd cycle for 57 and 55 pts respectively. If the early scan remained positive then additional 4 cycles of EB were administered, otherwise, SB was given. 108 pts 44 F64 M age 18–63y (median 33) who had at least 1 year of follow up are reported. The CR rate was 97%. The 4-yr disease free (DFS) and overall survival (OS) is 84% and 90% respectively at a median follow up of 35-month (5-70). The 4-yr DFS and OS are similar for standard and high risk patients. The disease progressed in 3/10 pts with an interim positive PET versus 1/40 negative scans (p&lt;0.03) and in 1/13 (8%) interim positive Ga67scan versus 7/44 (16%) negative scan (NS). Negative predictive value of early normal PET and GA67 scans are 98% and 84% respectively. Only one patient developed secondary leukemia following salvage therapy and high dose chemotherapy. One patient died during therapy from unrelated cause. Conclusion: PET is a useful tool for early interim decision regarding dose of chemotherapy. Early PET allowed for chemotherapy reduction in 80% of high-risk pts. Only 14% of standard risk patients required dose intensification. Similar DFS and OS can be obtained regardless of IPS. 6 cycles of risk adapted BEACOPP are effective. Standard Risk High Risk Standard BEACOPP Escalated BEACOPP Stage I, II ≥ Age 50yrs; ≥ 4 sites; “B” symptoms or Bulky, stage III,IV IPS 0-2 IPS 3-7

Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach

2017 ◽  
Vol 133 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Taryn B. Fay-McClymont ◽  
Danielle M. Ploetz ◽  
Don Mabbott ◽  
Karin Walsh ◽  
Amy Smith ◽  
...  
Keyword(s):  
Young Children ◽  
High Dose Chemotherapy ◽  
High Dose

scholarly journals Anecdotal Response to Amphotericin in a Patient with Probable Susac Syndrome: Implications in the Pathogenesis

2019 ◽  
Vol 32 (11) ◽  
pp. 727
Author(s):  
Raquel Gil-Gouveia ◽  
Natália Marto ◽  
Pedro Vilela ◽  
Ana Catarino
Keyword(s):  
Hearing Loss ◽  
Fungal Infection ◽  
Infectious Agent ◽  
Brain Biopsy ◽  
High Dose ◽  
Radiological Findings ◽  
Susac Syndrome ◽  
Infection Treatment ◽  
Immune Mediated

Susac syndrome is a rare, probably immune-mediated endotheliopathy presenting with encephalopathy, sensorineural hearing loss and retinal arterial occlusions. A 33-year-old female with Susac syndrome was worsening despite high-dose steroids so a brain biopsy was performed which suggested a possible fungal infection. Treatment with amphotericin B resulted in prompt reversal of symptoms and radiological findings, and no further symptoms occurred during 8 years of follow-up. A diagnosis of fungal infection was not confirmed. The etiology of Susac syndrome is unknown and this anecdotal observation suggests that an infectious agent susceptible to amphotericin might have caused or triggered Susac syndrome in this patient.

scholarly journals Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children’s Oncology Group Trial ACNS0333

2020 ◽  
Vol 38 (11) ◽  
pp. 1175-1185 ◽  
Author(s):  
Alyssa T. Reddy ◽  
Douglas R. Strother ◽  
Alexander R. Judkins ◽  
Peter C. Burger ◽  
Ian F. Pollack ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
High Dose Chemotherapy ◽  
Rhabdoid Tumor ◽  
High Dose ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Primary Analysis ◽  
Historical Cohort ◽  
Entire Cohort ◽  
Atypical Teratoid ◽  
Group Trial

PURPOSE Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients < 36 months of age compared with a cooperative groups’ historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS Of 65 evaluable patients, 54 were < 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients < 36 months of age compared with the historical cohort ( P < .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.

scholarly journals Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

2020 ◽  
Vol 8 (1) ◽  
pp. e000775 ◽  
Author(s):  
Danny Rischin ◽  
Michael R Migden ◽  
Annette M Lim ◽  
Chrysalyne D Schmults ◽  
Nikhil I Khushalani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Antitumor Activity ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Primary Analysis ◽  
Link Type ◽  
Phase 2 Study ◽  
Group 3 ◽  
Group 1

BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

scholarly journals Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up

2009 ◽  
Vol 45 (6) ◽  
pp. 1119-1120 ◽  
Author(s):  
M Magni ◽  
M Di Nicola ◽  
C Carlo-Stella ◽  
L Devizzi ◽  
A Guidetti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy And Safety ◽  
Long Term Follow Up
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