GMI-1271, a novel E-selectin antagonist, combined with induction chemotherapy in elderly patients with untreated AML.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2560-2560 ◽  
Author(s):  
Daniel J. DeAngelo ◽  
Brian Andrew Jonas ◽  
Pamela S. Becker ◽  
Michael O'Dwyer ◽  
Anjali S. Advani ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Remission Rate ◽  
Chemotherapy Resistance ◽  
Leukemic Cell ◽  
Hepatic Function ◽  
Hematologic Toxicity ◽  
Survival Pathways ◽  
Grade 3 ◽  
Acceptable Side

2560 Background: The outcomes for elderly patients (pts) with acute myeloid leukemia (AML) remain poor, therefore newer and less toxic therapies are urgently needed. The binding of E-selectin (E-sel), an adhesion molecule expressed in the bone marrow, to the leukemic cell surface activates survival pathways and promotes chemotherapy resistance. GMI-1271, a novel E-sel antagonist, enhances chemotherapy responses and protects from common toxicities in preclinical models (Becker ASH 2013; Winkler ASH 2013 and 2014). We report interim Phase 2 data for GMI-1271 plus chemotherapy in elderly untreated pts with AML. Methods: Pts ≥ 60 yrs with untreated AML, ECOG 0-2, and adequate renal and hepatic function were eligible. Prior treatment of MDS was allowed. GMI-1271 (10 mg/kg) was given 24 hrs prior, during and 48 hrs post induction with infusional cytarabine and idarubicin (7+3). Safety, tolerability, and anti-leukemia activity were assessed. Two cycles of induction were allowed and responders could receive consolidation with GMI-1271 plus intermediate dose cytarabine. Dose-limiting toxicity (DLT), defined as myelosuppression in the absence of disease or related Grade 3 (Gr) non-hematologic toxicity beyond day 42, was assessed in the first 3 pts. Results: 24 pts have been enrolled to date and 17 are evaluable for response. The median age was 68 years (range, 60-79) with 58% male pts, 50% secondary AML (sAML) pts and 25% with high-risk cytogenetics (by SWOG). The first 3 pts had no DLT, allowing enrollment to proceed. Common Gr 3/4 AEs included febrile neutropenia (47%), pneumonia (20%), pulmonary edema (13%) and non-fatal respiratory failure (13%). 2 pts died of sepsis within 60 days. The remission rate (CR/CRi) was 12/17 (71%). CR/CRi rate was 75% for pts with de novodisease and 67% for pts with sAML. E-sel ligand was expressed at high levels on blasts in the majority of pts. Conclusions: The addition of GMI-1271 to anthracycline-based induction chemotherapy in untreated elderly pts with AML demonstrates a high remission rate with acceptable side effect profile and low induction mortality. This study compares favorably to previous studies (Lancet, ASCO 2016). A randomized trial is being planned. Clinical trial information: NCT02306291.

Combination of Daunorubicin and Cytarabine Chemotherapy with Gemtuzumab Ozogamicin as Initial Therapy for Elderly Patients with Previously Untreated Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4636-4636
Author(s):  
Lisa A. Kujawski ◽  
Irene Ryan ◽  
Kent Griffith ◽  
Harry P. Erba
Keyword(s):  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Stopping Rules ◽  
Intermediate Risk ◽  
Early Stopping ◽  
Secondary Aml ◽  
Perforated Appendix ◽  
Grade 3

Abstract Acute myeloid leukemia (AML) is a hematopoietic neoplasm that primarily affects older adults. The prognosis for elderly patients with AML remains poor. Treatment with standard induction chemotherapy leads to response rates of only 30–50%. More effective therapies for this population are needed. Gemtuzumab ozogamicin (GO) is a humanized murine anti-CD33 monoclonal antibody linked to calicheamicin, a potent cytotoxic agent. GO has been shown to be effective in elderly patients with AML in first relapse with 26% achieving a remission. Phase II studies reveal CR rates of 20–25% when used as single-agent induction therapy for elderly patients with newly diagnosed AML, and encouraging results when GO was combined with standard induction chemotherapy in younger patients. From Oct. 2003 to Jan. 2005, 16 patients ≥ 55 years of age with previously untreated CD33+ AML received a combination of GO and standard induction chemotherapy. A two-stage study design was used with early stopping rules for lack of efficacy and veno-occlusive disease (VOD); if fewer than 7 of the first 16 patients achieved CR, the study would be terminated early. Treatment regimen: daunorubicin 45 mg/m2/day IV days 1–3, cytarabine 100 mg/m2/day continuous IV infusion days 1–7, and GO 6 mg/m2 IV day 4. If persistent AML was noted on a day 14 bone marrow biopsy, a second induction with daunorubicin 45mg/m2/day for 2 days and cytarabine 100 mg/m2/day for 5 days was given. Bone marrow biopsies were performed every 2 weeks until remission or refractory AML was documented. Post-remission therapy was at the discretion of the physician. Supportive care included filgrastim and interleukin-11 started day 14, allopurinol, acyclovir, and norfloxacin. Patients received acetaminophen, dexamethasone, and diphenhydramine prior to GO to help prevent infusion reactions. Patient characteristics: median age 68 years (56–78); 4 with secondary AML, 4 and 11 with poor and intermediate risk karyotypes respectively, 9 had a PS of ≤ 2. Results: 6/16 patients achieved a CR (37.5%), 2 PR (12.5%), 4 had no response (25%), and 4 died prior to a response evaluation (1 sepsis, 1 intracranial hemorrhage, 1 perforated appendix, and 1 with peripheral blasts suggestive of persistent disease). Based on early-stopping rules for lack of efficacy, the study was terminated after accrual of 16 patients. Of the 6 patients who achieved a CR, 2 had secondary AML, but all had an intermediate risk karyotype. 4 patients relapsed with a median relapse-free survival of 4.8 months (2.3–12.5 months). Two patients remain in a CR at 4 and 18 months from response. Of the 2 patients with a PR, both obtained a CR with a second cycle of induction chemotherapy. 1 patient relapsed within 4 months of response, and the other remains in a CR at 5 months. Treatment-related toxicities: grade 3–4 neutropenia (avg. duration 22 days) and thrombocytopenia (avg. duration 23 days), grade 2 infusion reaction in 2 patients, grade 2 GI bleed in 2 patients, grade 2 CHF in 1 patient, and grade 2 diffuse alveolar hemorrhage in 1 patient. Grade 3–4 neutropenic fever occurred in all patients, with 2 deaths from sepsis, and 1 patient with a perforated appendix who later died. 1 patient died from an intracranial hemorrhage. 12 patients developed grade 1–2 elevation of liver transaminases, but VOD was not observed. Conclusion: The addition of GO to standard induction chemotherapy did not appear to increase the CR rate above that expected with chemotherapy alone in previously untreated, elderly AML patients.

Safety and Efficacy of 90Y Ibritumomab Tiuxetan (Zevalin®) for Untreated FollicularNon-Hodgkin's Lymphoma (FL) Patients, An Italian Cooperative Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 100-100
Author(s):  
G. Pica ◽  
S. Nati ◽  
Umberto Vitolo ◽  
Sara Galimberti ◽  
Pier Luigi Zinzani ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Remission Rate ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
Multicenter Trial ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Highly Effective ◽  
Grade 3 ◽  
Treatment Safety

Abstract Abstract 100 90Y ibritumomab tiuxetan (Zevalin®) combines the targeting advantage of monoclonal antibody with the radiosensitivity of FL. Previous studies showed that Zevalin resulted safe and highly effective in relapsed/refractory indolent NHL, irrespective to prior treatment with rituximab. Based on these results, we designed a multicenter trial to evaluate the safety and the efficacy of “upfront” single-agent Zevalin in FL. The primary endpoint was the incidence of responses in terms of overall remission rate (ORR) and complete remissions (CR). The secondary endpoints were the treatment safety by monitoring hematology and biochemistry parameters as well as adverse events. Fifty patients, with a median age of 59 years (range, 35–81), were treated. Forty-eight percent had bone marrow involvement (<25%) and 14% an elevated LDH. Thirty-four percent of patients had high risk FLIPI. Forty-six patients were also assessed by qualitative and quantitative PCR for Bcl2/IgH or IgH clonal rearrangement, for total 30 cases PCR-positive (65.2%). Results: The ORR was 93% (45/48) with a CR rate of 82% (41/48). Twenty-six patients, who were PCR-positive at diagnosis, were assessed at week 14. Twenty out of 26 (77%) became PCR-negative. After a median follow up of 24 months, the 2-year EFS for all patients was 85%; moreover, 15 patients (55%), who were PCR-positive at diagnosis, maintain PCR negativity. As expected, the main toxicity was moderate myelosuppression, with 30% and 26% of patients developing Grade 3/4 neutropenia and thrombocytopenia, respectively. Very few patients required platelets transfusion (4%) or growth factor use (6%). None of the patients experienced grade 3/4 non hematologic toxicity. In conclusion, Zevalin is highly effective and safe treatment for newly diagnosed FL patients. In the next future, the role of radioimmunotherapy - i.e. including optimal sequencing with chemotherapy - should be established in randomized studies. Disclosures: No relevant conflicts of interest to declare.

A Phase 1/2 Study of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1068-1068 ◽  
Author(s):  
Anna B. Halpern ◽  
Megan Othus ◽  
Emily M Huebner ◽  
Kaysey F. Orlowski ◽  
Bart L. Scott ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Induction Chemotherapy ◽  
Research Funding ◽  
Phase 1 ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Grade 3 ◽  
Dose Levels

Abstract Introduction:"7+3" with standard doses of cytarabine and an anthracycline has remained the mainstay of induction chemotherapy for newly diagnosed AML. Since some studies have shown improved outcomes with high-dose cytarabine, cladribine, or escalated doses of anthracyclines, we conducted a phase 1/2 study (NCT02044796) of G-CLAM using escalated doses of mitoxantrone for newly diagnosed AML or high-risk MDS (>10% blasts). Methods: Patients≥18 years were eligible if they had treatment-related mortality (TRM) scores of ≤6.9 (corresponding to a predicted risk of early death with standard induction chemotherapy of ≤6.9%) and adequate organ function (LVEF ≥45%, creatinine ≤2.0 mg/dL, bilirubin ≤2.5 times upper limit of normal). Excluded were patients with uncontrolled infection or concomitant illness with expected survival <1 year. In phase 1, cohorts of 6-12 patients were assigned to 1 of 4 total dose levels of mitoxantrone (12, 14, 16, or 18 mg/m2/day, days 1-3, compared to 10 mg/m2/day used in standard dose G-CLAM previously established in relapsed/refractory AML). Other drug doses were G-CSF 300 or 480 μg/day (for weight </≥76 kg; days 0-5), cladribine 5 mg/m2/day (days 1-5), and cytarabine 2 g/m2/day (days 1-5). In phase 2, patients were treated at the maximum tolerated dose (MTD) of mitoxantrone. A second identical course of G-CLAM was given if complete remission (CR) was not achieved with cycle 1. Up to 4 cycles of consolidation with G-CLA (mitoxantrone omitted) were allowed if CR or CR with incomplete platelet or blood count recovery (CRp/i) was achieved with 1-2 cycles of induction therapy. Dose-limiting toxicities (DLTs) were: 1) grade 3 non-hematologic toxicity lasting >48 hours that resulted in >7-day delay of the subsequent treatment cycle; 2) grade ≥4 non-hematologic toxicity if recovery to grade ≤2 within 14 days, both excluding febrile neutropenia, infection or constitutional symptoms. Results: Among 33 patients (median age of 57.3 [range: 26-77], median TRM score 2.31 [0.16-5.90]) treated in phase 1, one DLT occurred at dose levels 3 and 4 (respiratory failure in both cases), establishing G-CLAM with mitoxantrone at 18 mg/m2/day as the MTD. Sixty-two patients, including 6 treated in phase 1, received G-CLAM at MTD. Patient characteristics were as follows: median age 58 (21-81) years, median TRM score 2.85 (0.06-6.73), with AML (n=52) or high-risk MDS (n=10). Cytogenetics were favorable in 6, intermediate in 44, and adverse in 12 (MRC criteria); 11 patients had NPM1 and 6 had FLT3 mutations. Fifty-two patients (83.9%, 95% confidence interval: 72.3-92.0%) achieved a CR (n=48 [77.4%: 65.0-87.1%]), or CRp/i (n=4 [6.5%: 1.8-15.7%]) with 1-2 cycles of therapy. Only 3 patients required 2 cycles to best response. Among the 48 CR patients, 43 (89.6%) were negative for measurable residual disease (MRDneg) by flow cytometry. Four patients had morphologic leukemia free state, 1 patient with myeloid sarcoma had a partial remission, 4 had resistant disease, and 1 died from indeterminate cause. One patient died within 28 days of treatment initiation (septic shock). Median times to an absolute neutrophil count ≥500/μL and a platelet count of ≥50,000/μL were 26 and 23 days. Besides infections and neutropenic fever, maculopapular rash, and hypoxia (fluid overload/infection-related) were the most common grade ≥3 adverse events. In addition to the phase 1/2 MTD cohort, there were 15 patients treated in an expansion cohort and 3 eligible patients treated off protocol with mitoxantrone at 18 mg/m2. For these 80 patients combined treated at MTD, the CR and CR/CRp/i rates were 76.3% and 81.2%. After multivariable adjustment, compared to 300 patients treated with 7+3 on the SWOG S0106 trial, G-CLAM with mitoxantrone 18mg/ m2 was associated with an increased probability of CR (odds ratio [OR]= 3.08, p=.02), CR/CRp/i (OR=2.96, p=.03), a trend towards improved MRDnegCR (OR= 3.70, p=.06), and a trend towards improved overall survival ([OS]; hazard ratio=0.34, p=.07). For the entire study cohort, the 6 and 12-month relapse-free survival were 73% (64-83%) and 62% (42-74%) and the 6 and 12-month OS were 89% (82- 96%) and 77% (67-88%). Conclusions: G-CLAM with mitoxantrone up to 18 mg/m2/day is well tolerated and has potent anti-leukemia activity. This regimen may warrant further randomized comparison with 7+3. We also plan to examine the addition of sorafenib to G-CLAM in newly diagnosed AML patients regardless of FLT3 status. Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding. Erba:Ariad: Consultancy; Gylcomimetics: Other: DSMB; Pfizer: Consultancy; Sunesis: Consultancy; Jannsen: Consultancy, Research Funding; Juno: Research Funding; Novartis: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy; Celgene: Consultancy, Speakers Bureau; Agios: Research Funding; Astellas: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Seattle Genetics: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding.

Use of anti-EGFR agents among elderly patients with metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Ashley James D'Silva ◽  
Efrat Dotan ◽  
Dwight D. Kloth ◽  
Andrew Beck ◽  
Steven J. Cohen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Elderly Patients ◽  
Treatment Initiation ◽  
Single Agent ◽  
Stage Iv ◽  
Cancer Center ◽  
Hematologic Toxicity ◽  
Kras Status ◽  
Grade 3

657 Background: Limited data are available regarding the tolerance of older mCRC patients to anti-EGFR therapy. To evaluate the treatment patterns and tolerability of cetuximab/panitumumab in this patient population, we conducted a retrospective review of elderly patients treated with these agents at Fox Chase Cancer Center between 2004-2010. Methods: Patients ≥ age 65 with mCRC treated with cetuximab/panitumumab were included in the analysis. Patient demographics, disease characteristics, treatment drugs and duration, KRAS status and overall survival were recorded. Toxicity evaluation included review of common hematologic and non-hematologic toxicities seen with these agents. Results: 118 patients were included; 100 received cetuximab and 18 received panitumumab therapy. The majority of patients were male (59.3%) with colon cancer (82.2%) and stage IV disease at presentation (50.8%). The median age at treatment initiation was 73 yrs (range: 65-90). Median overall survival was 510 days, and the median time on treatment 73 days. Most patients were treated prior to the incorporation of routine KRAS testing thus, KRAS status was available for 35 patients (29.7%) with 14.2% KRAS mutant tumors. 66% of cetuximab and 45% of panitumumab treatments were given in combination with another agent. The overall incidence of any grade 3/4 non-hematologic toxicity was 36% (34% for single agent; 37.8% for combination therapy). Common grade 3/4 non-heme toxicities were: hypomagnesemia-16.9%, diarrhea-10.2%, and rash-9.3%. Diarrhea and hypomagnesemia were more common among patients receiving combination therapy. The overall incidence of any grade 3/4 hematologic toxicity was 15.2% (6.8% for single agent ; 20.3% for combination therapy). Anemia was the most common heme toxicity in both single and combination therapy. Advanced age at treatment initiation was associated with higher incidence of single agent therapy (p=0.0005, ANOVA statistics). Conclusions: Our data demonstrate that elderly patients with mCRC tolerate anti-EGFR therapy, with toxicity rates similar to those reported in large clinical trials with younger patient populations. Older mCRC patients can safely receive anti-EGFR treatment as part of their therapy.

S-1 monotherapy for the treatment of elderly patients with advanced gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15671-e15671
Author(s):  
J. Lim ◽  
J. Kim ◽  
H. Yi ◽  
H. Kim ◽  
M. Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Early Death ◽  
Progression Free Survival ◽  
The Other ◽  
Subdural Hemorrhage ◽  
Hematologic Toxicity ◽  
Grade 3

e15671 Background: Elderly patients have often been excluded from clinical trials and only limited data are available regarding treatment of these patients. The efficacy of S-1 chemotherapy for elderly patients with advanced gastric cancer (AGC) is not well investigated. The aim of this study is to evaluate the efficacy and safety of S-1 monotherapy in elderly patients with AGC to whom conventional chemotherapy is difficult to deliver. Methods: From January 1, 2007 to August 31, 2008, a total of seventeen patients older than 70 were given S1 monotherapy. They received S-1 at a dose of 40mg/m2 BID either every 3 weeks (2 weeks on, 1 week off) or every 6 weeks (4 weeks on, 2 weeks off). Response was assessed according to RECIST criteria. Results: The patients consisted of 11 men and 6 women whose median age was 77 years (range: 71–83) with their performance status in 1 to 2. Five patients had recurrent AGC and the other 12 patients metastatic AGC at the time of diagnosis. Total 89 cycles of S-1 chemotherapy were given (median 4 cycles, range 2–12). Fifteen patients were evaluable for response because of early death in 2 patients. Response rate was 17.6% (95% Condifence Interval, 0 to 35.7); Complete remission in 0, partial remission in 3 (17.6%) and stable disease in 5 patients (29.4%). At a median follow up of 9.7 months (range: 8–11.4), median progression free survival was 5.1 months (range: 3.5–6.7) and overall survival was 9.5 months (range: 5.6–15.5). Most of the adverse effects of S1 monotherapy did not extend beyond grade 3. Grade 3 or 4 non- hematologic toxicities were not frequent and were easily manageable except in two, one of whom died of neutropenic sepsis and the other who died of subdural hemorrhage in grade 4 thrombocytopenia. Conclusions: S1 chemotherapy showed modest efficacy in elderly patients with AGC. The hematologic toxicity should be cautiously monitored in these elderly patients to avoid fatal events. Further studies are warranted for optimal management of elderly patients with metastatic or recurrent AGC. No significant financial relationships to disclose.

scholarly journals Rituximab, Bendamustine and Cytarabine (RBAC500) As Induction Therapy in Elderly Patients with Mantle Cell Lymphoma: Final Results of a Phase 2 Study from the Fondazione Italiana Linfomi

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 472-472 ◽  
Author(s):  
Carlo Visco ◽  
Annalisa Chiappella ◽  
Luca Nassi ◽  
Caterina Patti ◽  
Simone Ferrero ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Phase 2 ◽  
Advisory Committees ◽  
Ki 67 ◽  
Phase 2 Study ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: The combination of rituximab (R, 375 mg/m2 intravenously [IV], day 1), bendamustine (B, 70 mg/m2IV, days 2 and 3), and cytarabine (800 mg/m2, IV on days 2 to 4) was highly active in patients with mantle-cell lymphoma (MCL) in a phase 2 study [R-BAC; Visco et al, JCO 2013]. This regimen was well tolerated, but hematologic toxicity was quite relevant, especially in terms of transient grade 3 to 4 thrombocytopenia (76% of cycles). Aiming at reducing hematologic toxicity, the Fondazione Italiana Linfomi (FIL) designed a phase 2 trial adopting the R-BAC schedule, but lowering cytarabine dose to 500 mg/m2 (RBAC500). Materials and Methods: Patients with newly diagnosed MCL, aged 61 to 80 years, not eligible for autologous transplant and fit according to the comprehensive geriatric assessment, were enrolled. Patients presenting with non-nodal leukemic disease were excluded. The primary endpoints were complete remission rate (CR) measured by FDG-PET according to Cheson criteria 2007, and safety. Secondary endpoints included rate of molecular response (MR) by nested-PCR using patient specific IGH or BCL1 based targets, progression-free (PFS) and overall survival (OS). The study was conducted according to the Bryant and Day two-stage design. Results: From May 2012 to February 2014, 57 patients with MCL from 29 centers were recruited and treated. Central pathology revision was performed in 87% of cases. Median age was 71 years (range 61-79), 75% were males, and 91% had Ann Arbor stage III/IV disease. Mantle Cell International Prognostic Index (MIPI) was low in 15%, intermediate in 40%, high in 45%, Ki-67 was ≥30% in 31%, and 9% had the blastoid cytological variant. Overall, 53 patients (91%) received at least 4 cycles, while 36 (63%) had 6 cycles (median 5.3 cycles per patient). Fifteen patients (26%) discontinued treatment before reaching cycle 6 because of toxicity/adverse events, that mainly consisted of prolonged hemato-toxicity between cycles. Only one patient discontinued due to progressive disease. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 49% and 52% of administered cycles, respectively. Febrile neutropenia occurred in 6% of cycles. Extra-hematologic toxicity was mainly cardiac (5%). Overall response rate was 96%, and CR was 93%. The MR rate at the end of treatment was 76% on peripheral blood and 55% on bone marrow (BM) samples. With a median follow-up of 34 months (28-52), the 2-years PFS (± confidence interval) was 81%±5% and the OS 85%±4%. Elevated Ki-67 (≥30%), and the blastoid variant were the strongest independent predictors of adverse PFS. Patients with either of these two features (33%), had a significantly inferior PFS (41% vs 97% after 34 months) compared to patients with classical/pleomorphic variants and low proliferative index (p<0.0001, Figure 1). Conclusions: The R-BAC500 regimen can be safely administered as first line therapy to elderly patients with MCL. Hematologic toxicity is substantially reduced compared to our previous experience. With 93% of FDG-PET negative CR, and a 2-years PFS of 81% without maintenance therapy, the R-BAC500 regimen is a highly effective treatment for patients with MCL, and compares favourably with previously reported regimens in this patient population, including R-bendamustine. Figure 1 Figure 1. Disclosures Visco: Gilead: Speakers Bureau; Lundbeck: Consultancy; Mundipharma: Research Funding; Celgene: Speakers Bureau. Spina:Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee; Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee. Di Rocco:Celgene: Honoraria. Carella:Millenium: Speakers Bureau; Genentech: Speakers Bureau. Vitolo:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gilead: Honoraria; Celgene: Honoraria.

scholarly journals Standard 6-week chemoradiation for elderly patients with newly diagnosed glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Loïg Vaugier ◽  
Loïc Ah-Thiane ◽  
Maud Aumont ◽  
Emmanuel Jouglar ◽  
Mario Campone ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Real Life ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3 ◽  
Neurological Progression ◽  
Neurological Disabilities

AbstractGlioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72–77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I–II and III–IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5–17.5), median OS was 11.7 months (CI 95%: 10–13 months). Median PFS was 9.5 months (CI 95%: 9–10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.

Karyotype Plus NPM1 Mutation Status Defines a Group of Elderly Patients with AML (≥60 Years) Who Benefit From Intensive Post-Induction Consolidation Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2504-2504
Author(s):  
Wolfgang R. Sperr ◽  
Otto Zach ◽  
Iris Poell ◽  
Michael Kundi ◽  
Susanne Herndlhofer ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
Predictive Variables ◽  
Monosomal Karyotype

Abstract Abstract 2504 Whereas treatment strategies for AML patients (pts) aged <60 years are well established, therapy in the elderly deserves special consideration. In the present study, we analysed survival and risk factors predicting outcome in 192 consecutive patients (pts) with de novo AML aged ≥60 years (median age: 70.5 years, range 60–89 years). Pts were treated at a single center (Medical University of Vienna) between November 1994 and January 2011, and received conventional induction chemotherapy with DAV (daunorubicin, 45 mg/m2/day, days 1–3; etoposide, 100 mg/m2/day, days 1–5; ARA-C, 2 × 100 mg/m2/day, days 1–7; between 1994 and 2008). Pts achieving a complete hematologic remission (CR) were scheduled to receive a full consolidation program with up to 4 cycles of IDAC (ARA-C, 2 × 1 g/m2/day i.v. on days 1, 3, and 5). Of the 192 pts, 115 (60%) achieved a CR following induction therapy, 57 pts (30%) did not achieve a CR, and 20 pts (10%) died within 40 days after start of induction therapy. Among several parameter including the leukocyte count, hemoglobin, platelet count, LDH, and fibrinogen, only the karyotype according the the Breems-Score was an independent predictor for achieving CR in our multivariate analyses. CR rates in pts with core binding factor (CBF) AML, cytogenetically normal (CN) AML, non-monosomal karyotype (Mkneg) AML, and monosomal karyotype (Mkpos) AML, were 100% (8/8), 66% (57/87), 56% (33/59), and 44% (11/25), respectively (p<0.05). Of the 115 pts in CR, 106 (92%) received up to 4 cycles of IDAC (4 cycles, n=53 pts [50%]; 3 cycles, n=20 pts [19%]; 2 cycles, n=20 [19%]; and 1 cycle, n=13 [12%]). Treatment was well tolerated without grade 3 or 4 neurotoxicity. The most frequent non hematologic toxicity was febrile neutropenia requiring antibiotics (1st consolidation: 50.5%; 2nd consolidation: 58.4%, 3rd consolidation: 55.6%, 4th consolidation: 51.0%). A remarkable finding was that the median time of absolute neutropenia in all IDAC cylces (8–9 days/consolidation) was relatively short when compared to induction chemotherapy or other consolidation regimens. Only two patients died during consolidation with IDAC (cardiac failure, n=1, severe sepsis, n=1). The median overall survival (OS) for all pts was 9.7 months, and for pts achieving a CR, the OS amounted to 24.2 months. The most important predictive variables for continuous complete remission (CCR) were the karyotype and the presence of an NPM1 mutation determined by PCR and melting point analysis. As assessed by uni- and multivariate analysis, both parameters were found to be independent predictive variables (p<0.05), whereas the other markers examined, i.e. FLT3 ITD, overexpression of ERG, MN1, or BAALC, as well as the number of induction cycles required to achieve CR, showed no predictive value. The median CCR and CCR after 5 years were 17.9 and 31.3%, respectively in pts with CN/Mkneg-NPM1 mutated AML, and 11.3 months and 25% for pts with CBF AML (p<0.001; see figure). In pts with CN/Mkneg and wild type NPM1 AML and Mkpos AML, the median CCR rates were 10.8 and 6.0 months, respectively. Together, our data show that elderly patients with CN/Mkneg-NPM1 mutated AML or CBF AML can achieve long term CCR when treated with intensive chemotherapy and up to 4 consolidation cycles of IDAC, whereas pts with CN/Mkneg-NPM1 wild type AML and Mkpos AML did not achieve long term CCR despite intensive consolidation. These results are in favour of individualized chemotherapy in elderly pts with AML and suggest that patient-selection in advanced age should not only be based on patient-related factors and the karyotype but also on the NPM1 mutation status. Disclosures: No relevant conflicts of interest to declare.

Clinical and Pharmacologic Study of the Farnesyltransferase Inhibitor Tipifarnib in Cancer Patients With Normal or Mildly or Moderately Impaired Hepatic Function

2006 ◽  
Vol 24 (28) ◽  
pp. 4558-4564 ◽  
Author(s):  
Wandena S. Siegel-Lakhai ◽  
Mirjam Crul ◽  
Peter De Porre ◽  
Steven Zhang ◽  
Ilsung Chang ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Hepatic Function ◽  
Moderate Hepatic Impairment ◽  
Hematologic Toxicity ◽  
Pharmacokinetic Data ◽  
Impaired Hepatic Function ◽  
Normal Hepatic Function ◽  
Starting Dose ◽  
Grade 3 ◽  
The Individual

Purpose This study explored the feasibility of treating patients with impaired hepatic function with tipifarnib. The safety profile, pharmacokinetics, and relationship between the pharmacokinetics and toxicities were evaluated. Patients and Methods Patients with mildly or moderately impaired hepatic function (Child-Pugh classification) were treated with tipifarnib bid on days 1 to 5 of cycle 1. Further dosing was based on the individual day 5 pharmacokinetic data and absolute neutrophil count. For patients with normal hepatic function, tipifarnib was dosed on days 1 to 14, followed by 1 week of rest. For all patients, in subsequent cycles, tipifarnib was administered for 21 consecutive days out of every 28 days. Results Twenty-eight patients were included in the normal (n = 16), mild (n = 9), and moderate (n = 3) impairment groups. The most important grade 3 to 4 hematologic toxicity was leukocytopenia/neutropenia, which was mostly observed in patients with moderate impairment. Common nonhematologic toxicities were fatigue, nausea, and vomiting. The pharmacokinetic data showed higher plasma concentrations of tipifarnib in patients with liver impairment compared with patients with normal hepatic function. Conclusion In patients with mildly impaired hepatic function, tipifarnib can be administered safely at a starting dose of 200 mg bid, but it is not safe to treat patients with moderate hepatic impairment.

scholarly journals Old Does Not Necessarily Mean Worse: Standard Stupp Regimen for Elderly Patients (≥ 70 years) with Newly Diagnosed Glioblastoma

2021 ◽  
Author(s):  
Loig Vaugier ◽  
Loïc Ah-Thiane ◽  
Maud Aumont ◽  
Emmanuel Jouglar ◽  
Mario Campone ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Real Life ◽  
Treatment Decision ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Class Iii ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3 ◽  
Neurological Disabilities

Abstract Introduction Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard Stupp regimen in particular, although this is the mainstay for younger (<65 years) patients. Methods All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for Stupp treatment were reviewed from 2004 to 2018. MGMT status was not available for treatment decision. The primary endpoint was overall survival (OS). Secondary outcomes were relapse-free survival (RFS), early (≤ 1 month after RCT) adverse neurological events (symptoms of intracranial hypertension and/or use of corticosteroids and/or hospitalization) and temozolomide hematologic toxicity assessed by CTCAE v5. Results 128 patients were included. The median age was 74.1 (IQR: 72-77). 15% of patients were ≥80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I-II and III-IV, respectively. 81% of patients received the entire RCT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5-17.5), median OS was 11.7 months (CI95%: 10-13 months). Median RFS was 9.5 months (CI95%: 9-10.5 months). 60% of patients had early adverse neurological events, of whom 44% had progression and 8% experienced grade ≥3 hematologic adverse events. RPA class III-IV and occurrence of neurological events were associated with lower OS rates, whereas post-operative neurological disabilities were not. Age ≥80 was not associated with worsened outcomes. Conclusions Stupp radiochemotherapy was feasible and effective for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities.

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