A Prospective Study Evaluating the Safety and Efficacy of Combination Therapy with Fludarabine Plus Mitoxantrone Followed by Yttrium-90 (90Y) Ibritumomab Tiuxetan (Zevalin®) and Maintenance Rituximab as Front Line Therapy for Patients with Intermediate or High Risk Follicular Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1360-1360 ◽  
Author(s):  
Stephanie A. Gregory ◽  
Mohamad Kassar ◽  
Henry C. Fung ◽  
Parameswaran Venugopal ◽  
Teresa M. O’Brien ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Study ◽  
Response Rates ◽  
Stage Iii ◽  
Front Line ◽  
Ibritumomab Tiuxetan ◽  
Safety And Efficacy ◽  
Line Therapy ◽  
The Impact

Abstract Background: The combination of fludarabine and mitoxantrone (FM) as a front line therapy for advanced follicular lymphoma (FL) has been shown to result in higher complete response rates when compared with standard-dose CHOP. We assessed the safety and efficacy of FM followed by 90Y ibritumomab tiuxetan (IT) and maintenance rituximab (MR) in previously untreated patients (pts) with FL. Methods: Pts with newly diagnosed stage III-IV FL and an intermediate or high FLIPI scores were eligible. Pts were required to have an expected survival of at least 3 months, a performance status ≤2, and adequate bone marrow (BM) function (ANC 1500/mm3, platelets 100,000/mm3), liver, and renal function. Initial treatment consisted of 4 cycles of FM (fludarabine 25 mg/m2 on days 1–3, mitoxantrone 12 mg/m2 on day 1 of each 28-day cycle). After restaging, complete and partial responders with ≤25% BM involvement proceeded to the IT therapeutic regimen. Partial responders with >25% BM involvement received 2 additional cycles of FM before IT. The 90Y IT dose (0.3 or 0.4 mCi/kg) was adjusted according to the patient’s platelet count. MR (375 mg/m2 weekly× 4) was scheduled for every 6 months over 2 years. Results: Twenty patients have been enrolled. The median age was 53 years (range: 32–79), and 12 pts were male. 14 pts had stage IV with BM involvement and 6 had stage III. The median FLIPI score was 2 (range, 1–4). Only 1 pt had 6 cycles of FM. At the time of this analysis: 13 pts underwent therapy with IT, 3 of them finished MR cycles, 1 had 3 cycles, 5 had 2 cycles, 1 had 1 cycle, and 3 are still awaiting their first cycle of MR. 7 pts finished FM therapy but still awaiting treatment with IT. Overall response was achieved in 100% of pts; CR in 14/20 pts (70%) and PR in 6/20 pts (30%). The responses to FM were converted from PR to CR in 5 pts: 1 after IT, 1 after 2 cycles of MR, and 3 after completing MR. Grades 3 or 4 hematologic toxicities were encountered in 6/20 pts (30%); with grades 3 or 4 neutropenia in 5 pts (25%) and grades 3 or 4 thrombocytopenia in 5 pts (25%). Platelets, ANC, and hemoglobin nadirs occurred at 3–7 weeks following 90Y IT, and were reversible with median duration of nadirs of 4 weeks (range: 1–5). After median follow up of 16 months (range 3.5 – 39), only one pt developed progressive disease 14 months from registration, and after receiving IT therapy. Repeat BM biopsy at progression showed FL with focal areas of blastoid transformation. No death event has been reported to date. Conclusions: The initial results from this prospective study suggest: 1- FM followed by 90Y ibritumomab tiuxetan and maintenance rituximab regimen is safe and highly effective front line therapy for pts with intermediate or high risk FL (advanced stage with intermediate or high FLIPI scores at diagnosis). 2- The addition of IT and MR to the overall treatment strategy improves the quality of responses; and 3- Though the response rates are encouraging, longer follow-up will be required to evaluate the impact on progression-free survival and overall survival.

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

Alemtuzumab Plus Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Transplantation in Ultra High-Risk CLL: Interim Analysis of a Phase II Study of the GCLLSG and fcgcll/MW

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Florence Cymbalista ◽  
Véronique Leblond ◽  
Alain Delmer ◽  
Dirk Winkler ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Response Rates ◽  
Long Term Results ◽  
High Dose ◽  
Significant Difference ◽  
Ultra High Risk ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2854 Alemtuzumab (A) proved to be efficacious in CLL patients (pts) with very poor prognosis, either due to fludarabine (F) refractoriness or due to unfavorable cytogenetics (17p-). However, rate and duration of remissions still remain unsatisfactory. Therefore, the French and German CLL study groups jointly embarked on this trial, trying to achieve higher overall response rates (ORR) by adding high-dose dexamethasone (D) to A and, simultaneously, investigating the consolidation effect of prolonged A maintenance or allogeneic stem-cell transplantation (allo-SCT), respectively. Induction treatment consisted of subcutaneous A 30 mg weekly × 3 for 28 days, combined with oral D 40 mg on days 1–4 and 15–18, and prophylactic pegfilgrastim 6 mg on days 1 and 15. Depending on the remission status, pts were treated for up to 12 weeks. If CR was documented at 4 or 8 weeks, or at least SD was achieved at 12 weeks, consolidation was scheduled with either allo-SCT or A maintenance with 30 mg every 14 days for up to 2 years (y), at the discretion of pt and physician. Between January 2008 and July 2011, 124 pts were recruited at 26 centers, 120 of whom were eligible. Pts were generally subdivided into three cohorts: 55 pts were refractory (i.e. no response or relapse within 6 months) to regimens containing F or a similar drug (i.e. pentostatin, cladribine, bendamustine). Non-refractory pts all exhibited 17p- and had either untreated (n=39) or relapsed CLL (n = 26) requiring therapy. The median age was high with 66/64/66 y in 17p- 1st line, 17p- relapse, and F-refractory pts, respectively. The three cohorts had 46/54/75% Binet C disease, 41/35/27% B symptoms, 38/42/53% reduced performance status (ECOG 1/2), median thymidine kinase levels of 35/49/24 U/L, median ß2MG levels of 3.8/5.5/4.6 mg/L, and IGHV was unmutated in 89/96/87%. In the F-refractory group, 53% exhibited 17p deletion and 22% had 11q deletion. Pretreated patients had received a median of 3 (F-refractory) or 2 prior lines (17p- relapse). 5 pts had previously undergone autologous and 1 pt allo-SCT. Treatment and efficacy data are currently available for 87 pts who completed induction therapy :17p- 1st-line (n=30), 17p- relapse (n=17), and F-refractory (n=40). Of these, 80/53/55% received the full induction of 12 weeks. ORR (best observed status) was generally high with 97/76/70%. CR was achieved in 20/0/5%. After a median follow-up of 11.8 months (mo), median progression-free survival (PFS) was 16.9/10.4/8.4 mo. Deaths are recorded in 13/27/36% of pts, with median overall survival (OS) not yet reached (>24 mo) in the 17p- 1st line group, and 15/12 mo in 17p- relapse/F-refractory pts. Consolidation treatment was performed as maintenance A (median duration 32 weeks, range 2 – 89) in 34%, and allo-SCT in 30%, with a median age of 66 and 61 y in these subgroups. The main reasons for going off-study without consolidation were death due to infection (14%, n=11, of these 6 without response, and 10 in the F-refractory cohort), CLL progression (12%), and other toxicity (5%). Among the 28 pts not receiving consolidation, there were 19 (68%) deaths, 15 of them in the F-refractory cohort. When comparing A maintenance and allo-SCT for consolidation, there were 9 (35%) and 7 (30%) PD events, respectively and there was so far no significant difference in PFS (median 17 mo in both groups) or OS. During induction, grade 3/4 hematotoxicity consisted of anemia in 28%, neutropenia in 47%, and thrombopenia in 44%. Grade 3/4 non-CMV infection occurred in 29% of 17p- 1st-line, 15% of 17p- relapsed, and 56% of F-refractory pts. CMV reactivation was observed in 54/25/40%, without severe sequelae recorded. During A maintenance, grade 3/4 toxicity consisted of neutropenia in 39% pts and thrombopenia in 4% pts with 6 SAEs (ITP, diarrhea, infection, erythema, tachycardia, and thrombosis). Conclusions: The combination of A and D shows high response rates in ultra high-risk CLL, with promising preliminary findings for PFS and OS, despite the high median age of the pts. The results compare favorably to ORR/CR of 68%/5%, and median PFS of 11.3 mo in the 17p- subgroup of the CLL8 study treated with FCR, consisting of younger pts (median 61 y). In F-refractory CLL however, when compared to the preceding CLL2H study with single agent A, the improved initial response by adding dexamethasone does not seem to translate into improved long-term results. More mature follow-up is needed, especially with respect to the impact of allo-SCT. Disclosures: Stilgenbauer: Amgen: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding. Off Label Use: Alemtuzumab in 1st line CLL treatment. Cymbalista:Roche (d) Mundipharma (e) Genzyme (e): Honoraria, Research Funding. Hinke:WiSP (CRO): Employment.

Interest of the Association Azacitidine-Lenalidomide As Front Line Therapy in High-Risk Myelodysplasia (MDS) or Acute Myeloid Leukemia (AML) with Complex Karyotype

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5035-5035
Author(s):  
Elodie Scherman ◽  
Sandra Malak ◽  
Christine Perot ◽  
Norbert C. Gorin ◽  
Marie T Rubio ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Complex Karyotype ◽  
Front Line ◽  
Reduced Intensity Conditioning ◽  
First Line ◽  
Line Therapy ◽  
Acute Myeloid

Abstract Abstract 5035 Background. Results of intensive chemotherapy (ICT) in myelodysplasia (MDS) or secondary acute myeloid leukaemia (sAML) are poor, particularly in the presence of complex cytogenetic. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative treatment but only a minority of patients is eligible for HSCT notably because of difficulties to assess disease control underlining the need for novel strategies. Although, the use of hypomethylating agents has improved the overall survival (OS) of MDS with excess of blasts and might be interesting in AML (Fenaux, Lancet Oncol 2009), the prognosis of high risk MDS and AML remains poor (Itzykson, Blood 2011). Lenalidomide has demonstrated its efficiency in MDS with del5q and, has also been tested in patients with high-risk MDS or AML (Ades, Blood 2009). Aim. We report our experience of the association of azacitidine and lenalidomide in patients presenting with high risk MDS or sAML and who were unfit for ICT. Patients and treatment. Eight consecutive patients were referred to our haematological department from August 2008 to March 2010 with a diagnosis of high-risk MDS or sAML because of the presence of a complex karyotype including in all cases abnormalities of the 5q chromosome. At diagnosis, median age of patients was 66.5 years (range, 23–76); median WBC was 2×10.9/L (range, 0.11–7.1) and median marrow blast was 23% (range, 11%-37%). Four patients had secondary therapy-related AML and four patients had type-2 refractory anemia with excess of blasts (RAEB). None of them was eligible for an intensive chemotherapy because of age and/or poor performans status and/or comorbidities. They received cycles of 28 days of azacitidine (75 mg/m2 Day 1 to 5 or 7 SC) and lenalidomide (10 mg per day, day 1 to 14 or 21, oral) as first line treatment for a median of 4.5 cycles (range, 1–13 cycles). Results. Main side effects were cytopenias: 7 patients on the 8 developed grade 4 thrombocytopenia. Five patients, 4 with baseline ANC more than 1000/mm3 developed grade 4 neutropenia. Severe infections occurred in neutropenic patients: 6 sepsis (4 fevers of unknown origin, 1 facial cellulitis, 1 fungal infection and 1 CMV reactivation.) including 2 septic shock. However, no death was related to the toxicity of the treatment. Of the eight patients, 6 achieved a haematological response (3 complete response (CR), 3 partial response (PR)) and 2 progressed under treatment. Among the 6 responding patients, initial responses occurred at a median of 10 weeks (range, 6–28 weeks) from the beginning of therapy. Two patients were allografted, one with a reduced intensity conditioning in haematological and cytogenetic CR at transplant, and the other one with a sequential type reduced intensity conditioning in complete haematological but partial cytogenetic remission at HSCT. With a median follow-up of 60 weeks for the responding patients, (range, 0–72), the 4 responding patients who were not allografted because of age did experience relapse at a median of 12 weeks (range, 8–36 weeks) from initial response while the two patients who were allografted are still alive in CR at 15 and 14 months after HSCT, respectively. Considering the whole population, with a median follow up of 18 months, the median OS was 15 months (range, 1–18 months), and median progression-free survival (PFS) was 9.5 months (range, 0–18 months). Conclusion. The association of azacitidine and lenalidomide in the context of high risk MDS and sAML might offer a significant probability of remission with tolerable toxicity. For patients considered for an allogeneic HSCT, the use in first line therapy of such novel combination strategy rather than intensive chemotherapy represents an interesting option particularly in the case of complex cytogenetic. Disclosures: Off Label Use: Interest of the association Azacitidine-Lenalidomide as front line therapy in high-risk myelodysplasia (MDS) or acute myeloid leukemia (AML) with complex karyotype.

Phase II Study with R-FND Followed by 90-Y Ibritumomab Tiuxetan Radioimmunotherapy and Rituximab Maintenance for Untreated High-Risk Follicular Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 99-99
Author(s):  
Nathan H. Fowler ◽  
Sattva S. Neelapu ◽  
Michelle A. Fanale ◽  
Maria A. Rodriguez ◽  
Barbara Pro ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rates ◽  
Stage Iii ◽  
Ibritumomab Tiuxetan ◽  
Advisory Committees ◽  
Rituximab Maintenance

Abstract Abstract 99 Background: Follicular lymphoma (FL) patients (pts) with high-risk features using the FL International Prognostic Index (FLIPI) have an expected 5-year survival of approximately 50% with conventional chemotherapy. The incorporation of anti-CD20 monoclonal antibody therapy has improved results in this poor risk subgroup. (Buske, Blood 2006;108:1504) We have previously demonstrated that R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) is an effective regimen for indolent lymphoma, capable of inducing molecular remissions. (McLaughlin, ASCO 2003;102:564). Both extended dosing of rituximab following induction, and consolidation of first remission with 90-Y ibritumomab tiuxetan radioimmnotherapy (RIT) can improve complete response rates and progression free survival (PFS) rates for patients with advanced FL. (Morschhauser, JCO 2008;32:5156; Salles, Lancet 2011;377:42) This is the first report of a chemoimmunotherapy approach followed by both RIT consolidation and rituximab maintenance. Methods: Untreated patients with FL (grade 1–3), with high risk disease (FLIPI score ≥ 3) who had adequate hematologic function and extensive stage (III/IV) disease were eligible for study entry. Patients received rituximab (375mg/m2 days 1 and 8 of cycle 1, and day 1 of subsequent cycles) fludarabine (25mg/m2 days 1–3), mitoxantrone (10mg/m2 day 1), and dexamethasone (20mg days 1–5) for four 28 day cycles. RIT was given 12–16 weeks following R-FND pending hematologic recovery. Six weeks following RIT, patients received rituximab 375mg/m2 every two months for one year. The primary objective of the study was to determine the PFS rates based on 1999 International Working Group criteria. The secondary objectives included assessing the safety and tolerance of RIT and maintenance rituximab after R-FND, assessing the CR and overall response rates, and determining the overall survival following treatment. Results: Forty nine patients were enrolled and 47 received treatment between October 2004 and April 2009. Forty-six patients were eligible for efficacy analysis. The median age was 61 (37–78), 80% had bone marrow involvement, and all had stage III/IV disease. Twenty four (51%) patients had bulky disease (>5cm) and 42 (91%) had elevated β2M. Thirty six patients completed all planned courses of treatment. Eight patients did not receive RIT, two due to neutropenia after R-FND. One patient had progressive disease while on treatment. Following R-FND, the complete (CR + CRu) and partial response rates were 87% and 13%. With RIT consolidation, the CR rate increased to 91%. At a median follow up of 50 months, the projected five year overall survival and PFS rates were 93% and 74%. Toxicity was mainly hematologic. Grade ≥ 3 neutropenia and thrombocytopenia occurred in 57% and 35% of patients respectively. Thirty seven patients required growth factors and 17 patients required transfusions. The median time to hematologic recovery following RIT was 10 weeks. The most common non-hematologic adverse events (≥Gr 3) were fatigue (17%), dypsnea (13%), and myalgia (11%). There were 3 cases of myelodysplasia (MDS), one in a patient who did not receive RIT. Conclusions: The combination of R-FND followed by RIT intensification and rituximab maintenance results in OS and PFS outcomes that are better than traditional combinations in this high risk population. Given the potential for serious toxicity (eg. MDS) seen in this trial and other intensive treatment strategies, this approach may be most appropriate in high-risk FLIPI patients whose outlook with standard therapy is poor. Acknowledgments: This study was sponsored by Genentech and Spectrum. Disclosures: Fowler: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fanale:Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Younes:Genentech, SBIO, Seattle Genetics, Syndax, Sanofi-Aventis: Honoraria, Research Funding.

A Comparison of the Effectiveness of First-Line Chemoimmunotherapy Regimens for Follicular Lymphoma (FL) Used in the United States

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 97-97 ◽  
Author(s):  
Loretta Nastoupil ◽  
Rajni Sinha ◽  
Michelle Byrtek ◽  
Michael Taylor ◽  
James R Cerhan ◽  
...  
Keyword(s):  
Research Funding ◽  
Response Rates ◽  
Practice Setting ◽  
Front Line ◽  
First Line ◽  
Poor Risk ◽  
Line Therapy ◽  
The Us ◽  
Baseline Characteristics

Abstract Abstract 97 Background: There is no consensus or standard of care for front-line therapy for FL as demonstrated by our initial publication of the National LymphoCare Study (NLCS) showing that strategies used in newly diagnosed FL patients (pts) in the US included: watchful waiting (17.7%), rituximab (R) with chemotherapy (51.9%), R alone (13.9%), radiation therapy (5.6%), chemotherapy (3.2%), or a clinical trial (6.1%). Given the lack of observational data comparing the effectiveness of front-line R-chemotherapy regimens, we examined the outcomes for patients with stage III/IV FL receiving R with cyclophosphamide, vincristine, and prednisone (RCVP), R with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), or R with a fludarabine-based regimen (RFlu) as first-line therapy. Methods: The NLCS is a prospective, multicenter, observational study collecting data on 2,738 previously untreated patients (pts) with FL diagnosed from 2004 to 2007 at 265 sites in the US. Initial management decisions were made by the treating physician without protocol-specified treatment assignments. Descriptive statistics for the baseline characteristics of pts who received RCVP, RCHOP, and RFlu were compared using Pearson Chi-square tests. A generalized logistic model was used to identify baseline factors of clinical interest (FLIPI, sex, practice setting [academic vs. community]) that were correlated with treatment. Kaplan–Meier estimation was used to evaluate progression-free survival (PFS) and overall survival (OS) for the treatment regimens; comparisons for the 2-year landmark estimates were obtained using a Wald statistic. PFS was defined as the number of days from diagnosis up to and including the date of progressive disease (PD) as assessed by the treating physician or death from any cause. Pts who had not yet experienced PD at the time of analysis were censored at the date of the most recent response assessment. To evaluate the effects of treatment on PFS and OS, Cox proportional hazards models were used controlling for FLIPI, sex, community or academic practice setting, and maintenance R or observation following treatment. Results: Of the 2,738 pts enrolled in NLCS, 926 pts were identified as having stage III/IV FL and having received the regimens of interest. Within this cohort 60% received RCHOP (n=558), 27% received RCVP (n=247) and the remaining 13% received RFlu (n=121). Baseline characteristics were correlated with induction treatment and whether a patient received subsequent R maintenance. Women (odds ratio [OR]=1.50, 95%CI 1.05–2.13) and pts aged >60 years (OR=2.36, 95%CI 1.64–3.38) more commonly received RCVP than RCHOP, and pts with LDH > upper limit of normal (OR=1.75, 95%CI 1.02–3.03) more commonly received RCHOP than RFlu. A greater % of pts receiving RCVP (61%) had poor-risk FLIPI (3–5) vs. RCHOP (49%) or RFlu (44%). In this cohort, 60% of RCVP, 43% of RCHOP, and 46% of RFlu pts received maintenance R. The overall response rates for RCVP, RCHOP, and RFlu were 88%, 94%, and 96%, respectively, and 2-year PFS was 72% (95% CI 66–78%) for RCVP, 78% (95%CI 74–81%) for RCHOP, and 76% (95%CI 67–-83%) for RFlu. There were no significant differences in PFS between treatments after adjustment (p= 0.07). However, with a median follow-up of 58 months there were significant differences in unadjusted OS (p=0.03), with 2-year OS probabilities of 88% (95%CI 84–92%) for RCVP, and 91% (84–95%) for RFlu, and 94% (92–96%) for RCHOP (Figure A). After adjustment for sex, FLIPI, practice setting, and maintenance use, the OS benefits of RCHOP persisted over RCVP HR=1.67 (95%CI 1.15–2.42) but not RFlu HR=0.94 (0.53–1.68). The benefits of RCHOP were even more pronounced in poor risk FLIPI pts (Figure B). Conclusions: First-line R-chemotherapy regimens in clinical practice have high overall response rates and high 2-year PFS and OS. With 4.75 years of follow-up in this large pt cohort, these regimens appear similar in response rates and early PFS and OS with suggestions that RCHOP may provide benefits over RCVP particularly for poor risk patients. Disclosures: Sinha: Celgene: Research Funding. Friedberg:Genentech: Consultancy; astellas: ; Lilly:; Abbott/Trubion:; Seattle Genetics: Honoraria; Cephalon: Consultancy. Hirata:Roche: Equity Ownership; Genentech Inc/Roche: Employment. Flowers:Seattle Genetics: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech/Roche (unpaid): Consultancy; Novartis: Research Funding; Spectrum: Consultancy, Research Funding.

scholarly journals Oral Arsenic Trioxide in Front Line Therapy for Acute Promyelocytic Leukemia. A Prospective Costa Rican Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3838-3838 ◽  
Author(s):  
Mariela Rodriguez ◽  
Ronald Rojas ◽  
Alejandra Vargas ◽  
Miguel Angel Rodriguez ◽  
Claudia Garcia ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Oral Formulation ◽  
Promyelocytic Leukemia ◽  
Front Line ◽  
Line Therapy ◽  
Grade 3

KEY WORDS: Acute Promyelocytic Leukemia, oral Arsenic Trioxide, ATRA, Front Line Therapy. CONTEXT: Studies showed the combination of all-trans-retinoic acid (ATRA) with Arsenic trioxide (ATO) as an effective treatment of patients with newly diagnosed Acute Promyelocytic Leukemia (APL), permitting a chemotherapy-free treatment approach. Oral formulations of ATO were developed with similar efficacy compared to the IV formulation, and a slightly safer profile. OBJECTIVE:To determine the effectiveness and safety of a locally produced oral ATO with ATRA as a first line therapy in APL. DESIGN:We designed the LPCR05 protocol based on established treatment protocols. Treatment regimen: Induction phase: all patients received ATRA (45 mg/m2 daily) and an locally produced oral formulation of ATO (10 mg daily), with a dose of Idarubicin (12 mg/m2 on days 1,3,5 and 7, if older than 60 years only given on day 1) added only to the high-risk patients. Consolidation Phase: 3 cycles of ATO + ATRA for 30days every 6 weeks. Maintenance Phase: 4 Cycles of ATRA+ATO daily for 15 days every 3 months. Oral formulation for ATO is prepared by the Laboratory of Pharmaceutical Products from our Social Security System according to the literature and approved by local health and pharmaceutical regulators. RESULTS: We report data on our first 26 APL patients enrolled on the LPCR05 protocol. Six patients were classified as high risk, eighteen intermediate and two low risk (Table 1). One high risk patient discontinued after first consolidation because of lost follow up. The median follow up is 12.5 months. Hematological complete remission was obtained after 30 days of treatment in all 26 patients. Molecular complete remission in 22 evaluated patients after first and third consolidation was achieved in 95% and 100% respectively (Table 2). None of the patients have relapsed. There were no withdrawals of the protocol because of side effects and no induction deaths because of coagulopathy. No severe cardiac or neurological toxicity was found. Grade 3 hepatic toxicity was seen in two patients, in both cases, temporary discontinuation of ATRA and ATO resolved the side effect. One patient developed non treatment related grade 3 renal toxicity and other one developed a probably related grade 3 skin toxicity. Severe infectious complications were seen in three patients, two had pneumoniae (one death) and one enteritis (Table 3). Patients are managed in the ambulatory setting, with fewer hospitalizations (mean hospitalization days per patient of 38,1 with ATRA + chemotherapy vs 14,1 with oral ATO and ATRA), and therefore the cost is three times lower (US$65 208 vs US$24 195) than our previous approach with ATRA + chemotherapy protocol. CONCLUSION: Our data demonstrate both efficacy and safety of oral ATO with ATRA as front line therapy in all risk groups. This strategy also demonstrated lower operational costs, fewer hospitalization days, and improved convenience for patients. We expect longer follow-up will confirm that treatment with oral ATO and ATRA is a curative therapeutic strategy for patients with APL that is particularly attractive for use in low and medium income countries. Disclosures No relevant conflicts of interest to declare.

Cohort Analysis of Patients With Localized, High-Risk, Extremity Soft Tissue Sarcoma Treated at Two Cancer Centers: Chemotherapy-Associated Outcomes

2004 ◽  
Vol 22 (22) ◽  
pp. 4567-4574 ◽  
Author(s):  
Janice N. Cormier ◽  
Xuelin Huang ◽  
Yan Xing ◽  
Peter F. Thall ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Local Therapy ◽  
Distant Recurrence ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Clinical Benefits ◽  
The Impact

Purpose Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) have high risks of distant recurrence and death. The role of chemotherapy for these patients remains controversial despite several randomized trials and a meta-analysis. Methods We reviewed the treatments and outcomes of 674 consecutive adult patients presenting with primary stage III extremity STS between 1984 and 1999. Pre- or postoperative doxorubicin-based chemotherapy was used in a nonrandomized fashion in approximately half of this high-risk population. The objective of this review was to evaluate the impact of chemotherapy while accounting for known prognostic variables. Results Among 674 patients, 338 (50%) were treated with local therapy only, and 336 (50%) were treated with local therapy plus chemotherapy. The median follow-up for survivors was 6.1 years. Five-year local and distant recurrence-free interval probabilities were 83% and 56%, respectively, for the two groups combined. The 5-year disease-specific survival (DSS) rate was 61%. Cox regression analyses showed a time-varying effect associated with chemotherapy. During the first year, the hazard ratio associated with DSS for patients treated with chemotherapy versus no chemotherapy was 0.37 (95% CI, 0.20 to 0.69; P = .002). Thereafter, this hazard ratio was 1.36 (95% CI, 1.02 to 1.81; P = .04). Conclusion It seems that the clinical benefits associated with doxorubicin-based chemotherapy in patients with high-risk extremity STS are not sustained beyond 1 year. These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up.

Early Safety and Efficacy Analysis of a Phase II Study of Sequential R-CHOP and Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) for Elderly High Risk Patients with Untreated DLBCL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 926-926 ◽  
Author(s):  
Paul A. Hamlin ◽  
Craig H. Moskowitz ◽  
Brett C. Wegner ◽  
Carol S. Portlock ◽  
David J. Straus ◽  
...  
Keyword(s):  
High Risk ◽  
Sudden Death ◽  
Elderly Patients ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Safety And Efficacy ◽  
Grade 5 ◽  
Grade 3 ◽  
Yttrium 90

Abstract Introduction: Elderly patients (pts) with high risk DLBCL represent an increasing demographic, are often underserved in clinical trials, and need improved therapies. By the age-adjusted international prognostic index (aaIPI), pts &gt;60 years (yrs) with high-intermediate (HI) and high risk (H) disease had 5 yr survival (OS) rates of 37%, and 21%, respectively. Rituximab’s addition to CHOP has improved responses and outcomes, but &gt;50% of high risk pts still relapse. We are investigating the safety and efficacy of sequential RCHOP followed by Yttrium-90 ibritumomab tiuxetan (Zevalin ®) radioimmunotherapy (RIT) in an effort to improve these results. An early safety analysis of this sequential program is presented here. Methods: Untreated ASCT-ineligible pts &gt;60 yrs, with aaIPI HI or H risk DLBCL are eligible for study. Induction: pts receive R-CHOP chemotherapy at standard doses q 21 days x 6 cycles with prophylactic pegfilgrastim (or G-CSF) and darbepoetin alfa (Aranesp ®) support. Consolidation: pts with ≥ stable disease at post RCHOP restaging are eligible for 90Y-90 ibritumomab tiuxetan, given 6–9 weeks post RCHOP; For platelet (plt) counts ≥ 150K → 0.4 mCi/kg dose, plt counts of 100–149K → 0.3 mCi/kg. Weekly CBC’s are performed until week 12–13 restaging. Results: 26 pts have been enrolled as of July 12th, 2005. Median age is 75 (range 65–85; male:female 9:17); KPS &lt;80% in 55% (median 70%, range 60–90%); LDH &gt; nl: 89% (range 150–804); Stage III/IV: 11.5% / 88.5 %; Extranodal sites are &gt;1 in 50%; B symptoms in 54%; aaIPI HI (2 factors) = 46%, H (3 factors) = 54%; 18/26 pts have completed RCHOP; 8 pts are off study before RIT for: 4 cardiovascular events (1 CHF,1 Non-Q-wave MI, 1 sudden death, 1 V. Fib arrest), 3 neutropenic sepsis (1=grade 4, 2=grade 5), 1 leptomeningeal progression; 14 pts have received RIT. Median nadir counts during RIT occur at week 6–7: absolute neutrophil count (ANC) = 850 cells/mm3 (0.3–5.4), Hemoglobin (Hgb)= 10.1 gm/dl (6.6–14.6), plt = 28K cells/mm3 (7–103); Grade 3 and 4 ANC = 39%/39%, Hgb 39%/0%, Plt 46%/15%; During RIT, blood and Plt transfusion occurred for 46% and 31%, respectively; colony stimulating factor and erythropoietic support was used in 39% and 31%, respectively. One pt had delayed count recovery post RIT (448 days, transfusion independent from week 12→). Non-hematologic serious adverse events after RIT include: two grade 3 neutropenic infection (1 without fever), 1 grade 5 sudden death at week 7 (autopsy refused). OS and EFS for all pts by intent to treat is 60% and 55%, respectively, with 14 months median followup. Of pts post-RIT &gt;12 weeks (11 pts), none have relapsed with 21 months median follow-up. Conclusions: Treatment of elderly aaIPI HI and H risk DLBCL pts with sequential RCHOP followed by 90Y ibritumomab tiuxetan is feasible and associated with manageable toxicity. Hematologic toxicity with RIT is similar to single agent toxicity, with slightly greater thrombocytopenia that warrants careful follow-up. Toxicity during RCHOP induction is significant in high risk elderly patients and cycle one modification is being implemented. Accrual continues to evaluate the potential long term impact of RIT on EFS and OS.

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