Phase II trial of chemotherapy with high-dose FOLFIRI plus bevacizumab in the front-line treatment of patients with metastatic colorectal cancer (mCRC) and genotype UGT1A1*1/ UGT1A1*1 or UGT1A1*1/ UGT1A1*28 (FFCD 0504 trial). Results of a planned interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4065-4065
Author(s):  
E. Mitry ◽  
O. Bouché ◽  
L. Dahan ◽  
F. Bonnetain ◽  
P. Laurent-Puig ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Trial ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
Group 2 ◽  
Group 1

4065 Background: The antitumor efficacy of irinotecan may be dose dependent. In a recent phase II trial, the combination of high-dose irinotecan (260 mg/m2) with LV5FU2 regimen was feasible with an acceptable safety profile and promising efficacy data (Ducreux et al. Oncology 2008;74:17–24). The aim of this study was to evaluate the association of the high-dose FOLFIRI plus bevacizumab in patients (pts) selected on the UGT1A1 polymorphism, which could be predictive of the irinotecan toxicity. Methods: Pts with UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotypes and previously untreated mCRC were treated with bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1 and 5FU 2400 mg/m2 46h infusion D1–2 every 2 weeks. Using Bryant & Day design with OR (independent review, H0 ≤ 40%; H1 : ≥ 60%) and toxicity (gr 4 neutropenia or febrile neutropenia or gr3–4 diarrhea; H0 ≥ 20%; H1≤ 5% ) as primary endpoints; a total of 108 pts, 54 in each group, was required (alpha 5% and power 80%) with a planned interim analysis after the inclusion of 17 pts by group. The trial will be stopped at interim analysis if ≤ 7 pts had an OR and/or ≥ 3 pts had a severe toxicity. All analyses were performed in ITT. Results: At the time of interim analysis, done for group 1 when the 17th pt had a 6-months follow-up, 96 pts have been included (group 1: 40 pts, group 2: 46 pts). An objective response rate was observed in 9/17 pts but 7/17 pts had a severe toxicity (gr 4 neutropenia: 2 pts, febrile neutropenia: 2 pts, gr 3 diarrhea: 4 pts). Overall, 14/17 pts had a gr3–4 toxicity. There was no toxic death. According to interim analysis rules, the trial was closed to inclusion (for both groups) on December 16th 2008 for toxicity. The interim analysis for pts of group 2 is planned for February 2009 when the 17th patient will have a 6-months follow- up. Conclusions: High-dose FOLFIRI plus bevacizumab, although effective, was associated with a high toxicity rate among pts with UGT1A1 *1/*1 genotype. Complete tolerance, efficacy and survival results for all included patients will be presented at the meeting. [Table: see text]

A multicentric prospective study of intensive induction chemotherapy (API-AI) in localized osteosarcoma patients: Results of a phase II trial coordinated by the French Sarcoma Group (FSG) and the FNCLCC BECT

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9521-9521 ◽  
Author(s):  
S. Piperno-Neumann ◽  
B. Bui ◽  
J. Blay ◽  
H. Roché ◽  
F. Pichon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Dose Intensity ◽  
Poor Responders ◽  
High Dose ◽  
Severe Toxicity ◽  
Salvage Regimen ◽  
The Impact

9521 Background: Based on the severe toxicity of high dose methotrexate (MTX) in adult patients, an alternative intensive chemotherapy (CT) was designed, associating doxorubicin, cisplatinum and ifosfamide in API-AI regimen. Promising results in 32 patients in a single institution study (Le Cesne ASCO 2004) led to a national multicenter phase II trial coordinated by the FSG of FNCLCC. Methods: Patients with a localized operable osteosarcoma were eligible. API-AI regimen consisted in 2 cycles every 28 days of doxorubicin 60 mg/m2 d1 and d15, cisplatinum 100 mg/m2 d1 and ifosfamide 5g/m2 d2 and d15, with equivalent dose of mesna and lenograstim after each course for 7 days. Good responders ≥95% necrosis (GR) received 2 postoperative API courses, and poor responders <95% necrosis (PR) a salvage regimen of 3 cycles of etoposide 100 mg/m2 d1 to d3 and ifosfamide 4 g/m2 d1 to d3. Results: From March 2001 to January 2004, 43 patients (male/female 28/15) with a median age of 23 years (range 17–50), were included. The median tumor size was 88 mm (13–280). All 43 patients received the preoperative API-AI regimen, with a dose intensity of ≥ 89% of the planned protocol. Toxicity was mainly haematological, with grade 3–4 sepsis, grade 4 neutropenia and thrombocytopenia observed in 12%, 79% and 49% of patients respectively. There was no severe renal and cardiac toxicity. All but 5 patients had a limb sparing surgery performed 77 days (median) after the first cycle (range 56–114 days). Intent to treat analysis showed 16/43 GR (37%). With a median follow-up of 36 months (25–48), the 2 year event-free and overall survival were 74% and 86% respectively. Conclusions: Despite the haematological toxicities, these results compare favorably with other previous induction CT schedules containing MTX in adults. A longer follow-up is required to evaluate the impact of this regimen on overall survival. No significant financial relationships to disclose.

Multicentric phase II trial of gemcitabine plus capecitabine combination in the treatment of previously anthracycline(An)-treated metastatic breast cancer (MBC): SOLTI 0301 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1051-1051 ◽  
Author(s):  
E. M. Ciruelos ◽  
J. Baselga ◽  
H. Cortes-Funes ◽  
A. Lluch ◽  
J. I. Mayordomo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Clinical Activity ◽  
Her2 Overexpression ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

1051 Background: Based on clinical activity of capecitabine(C) and gemcitabine (G) on the treatment of MBC, we performed a multicentric phase II trial of the combination to test its efficacy and safety profile. Methods: Sample size of 72 evaluable MBC patients (pts) previously An-treated (neoadjuvant 8%, adjuvant 69%, advanced 30%). Median age: 59 years (35–76 years). Estrogen Receptor positive: 47 (65%). HER2 overexpression: 16 (22%). Prior hormonal/trastuzumab allowed. Soft tissue/ganglionar/pleural/bone disease: 19 (26%); visceral metastasis: 53(74%). Stratification: previous chemotherapy (CT) for advanced disease (none: group 1; any: group 2). Study treatment: oral bid C 1,660 mg/m2/day (d) (d1–14) + iv G 1,000 mg/m2/d (d1&8). Cycles repeated every 3 weeks. RECIST/NCI-CTC 2.0 criteria. Primary end point: Objective Response Rate. Results: Response Rates and Clinical Benefit (CB) are detailed in the table . Median follow-up 7.2 months (m) (0.2–18.4). Median time to progression 11.2 m: group 1, 12 m (95%CI: 6.4–14.5); group 2, 8.9 m (95%CI: 6.9–14).Total and median administered cycles/pt: 479 and 8. Delayed cycles: 103(21.5%): 27% due to hematological toxicity, 11% due to non-hematological toxicity, 62% due to other causes. C dose reduced in 27 cycles (5.6%), 12 of them due to non- hematological toxicity. G dose reduced in 169 cycles (35%), mostly on day 8, and due to hematological toxicity (80% of reduced cycles). Grade 3–4 neutropenia: 32 pts (56%), 1 case of febrile neutropenia. Grade 3–4 non-hematological toxicities: asthenia 8 pts (14%), hand- foot syndrome 6 pts (10.5%), mucositis 3 pts (5%), diarrhea 2 pts (3.5%). Conclusions: Combination of C+G in the treatment of previously anthracycline-treated MBC is safe and active, with a manageable toxicity profile and a good clinical activity. [Table: see text] No significant financial relationships to disclose.

Phase II trial of high-dose interleukin-2 (IL-2) and stereotactic radiation therapy (SABR) for metastatic clear cell renal cell carcinoma (ccRCC): Interim analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 532-532 ◽  
Author(s):  
Raquibul Hannan ◽  
Dan Ishihara ◽  
Kristi Louder ◽  
Chul Ahn ◽  
Vitaly Margulis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Trial ◽  
Interleukin 2 ◽  
Outcome Analysis ◽  
High Dose ◽  
Cell Renal Cell Carcinoma ◽  
Number Of Patients ◽  
Grade 3

532 Background: We report a planned interim analysis of a single-arm, open-label, phase II trial of HD IL-2 and SABR in multiple ccRCC metastatic sites. Methods: Metastatic ccRCC patients eligible for IL-2 were enrolled and received SABR of 1 or 3 fractions (fx) to up to 6 sites. IL-2 (Proleukin) was administered within 84 hours from the last SABR fx at 600,000 IU/kg every 8h for up to 14 doses in a monitored setting followed by another week after a week break. Eligible (responding) patients received a second course in > 12 weeks. The primary endpoint is the response rate (RR) as evaluated by iRECIST. The study is powered to detect a 60% improvement compared to the historically reported 23% RR for IL-2. Results: 16 patients were enrolled between August 2013 and July 2015; two were withdrawn from the study due to cardiac events prior to receiving IL-2 infusions. The median follow up was 9 months. A median of 2 (1-3) sites were treated with SABR with a median dose of 24.5 Gy (21-27 Gy) for single fx and 30Gy for 3 fx (25-33 Gy). All patients received the first week of IL-2 with a median of 10.5/14 doses; 64% received the second week (9/14) with a median of 7/14 doses. Two patients refused a second week of IL-2 and one was unable to receive it due to thyrotoxicosis. PICC line DVT delayed the second week of IL-2 in two patients. 29% of patients (4/14) received a second course of IL-2. The rate of grade 3 toxicity was 64% with no > grade 3 toxicity. The overall toxicities were expected of IL-2 treatment, transient and resolved after treatment discontinuation. In two cases, grade 1 toxicity was attributed to SABR. At this interim, ten patients underwent at least two follow up scans and were evaluable for outcome analysis. The RR was 40%, with one patient presenting complete response and 3 patients showing partial response. The median duration of overall response was 5 months, with a median stable disease duration of 6 months. Local control rate for SABR-treated lesions was 95%. Conclusions: The addition of SABR to IL-2 increased the RR in mRCC patients of about 2-folds compared to IL-2 alone, despite the reduced number of patients receiving the second week of IL-2. No significant increase in toxicity was observed. Clinical trial information: NCT01896271.

scholarly journals Efficacy of Chemotherapy or Chemo-Anti-PD-1 Combination after Unsatisfactory Response of Anti-PD-1 Therapy for Relapsed and Refractory Hodgkin Lymphoma: A Retrospective Series from Lysa Centers

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 652-652
Author(s):  
Cédric Rossi ◽  
Julia Gilhodes ◽  
Marie Maerevoet ◽  
Charles Herbaux ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Complete Response ◽  
High Rate ◽  
High Dose ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Hodgkin lymphoma (HL) pts who relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV) therapy have a poor outcome. For these relapsed and refractory (R/R) HL pts, anti-PD-1 therapy gives a high rate of objective responses. However, the rate of complete response (CR) remains modest and in the updated results of anti-PD-1 therapy clinical trials, about 50% of pts are still without progressive disease after one year of treatment. As anti-PD-1 therapy modifies the anticancer immune response, we hypothesize that anti-PD-1 therapy may increase sensitivity to chemotherapy (CT) given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). We retrospectively analyzed these two clinical situations in 30 R/R HL pts from LYSA centers treated with anti-PD-1 therapy. Methods: We included R/R HL pts from 14 LYSA centers who received anti-PD-1 therapy in the context of clinical trials (N=4) or an authorization for temporary use (ATU) from the French medical drug agency (N=26). Before the anti-PD-1 therapy, pts had received a median of six (range, 2-14) lines of therapy, 69% had HDT+ASCT, 14% had allograft and 93% had been treated with BV. We considered two groups of pts: i. 19 pts (63%) in whom the anti-PD-1 therapy was stopped at the introduction of CT (Group 1); ii. 11 pts (37%) with an unsatisfactory response to anti-PD-1 therapy in whom a combination of CT with immunotherapy was initiated to optimize the response (Group 2). The quality of the response after the introduction of CT was evaluated retrospectively by each treating physicians according to Cheson 2007 or 2014 criteria. We also determined whether new CT treatments after and in combination with anti-PD-1 therapy led to unexpected toxicities and whether new treatment schedules made pts eligible for allograft. Results: At the start of anti-PD-1, the median age of pts was 37 years old (range, 20-75), 24% had Ann Arbor III/IV stages, 34% had B symptoms and 21% had a performance status (PS) of 2-3. Patients received a median of 10 infusions (range, 2-52) of anti-PD-1 therapy with nivolumab (N=26, 87%) or pembrolizumab (N=4, 13%). The best responses achieved during anti-PD-1 therapy were a complete response (CR) for 5 patients, a partial response (PR) for 17 pts, stable disease (SD) for 2 pts and progression for 6 pts. In group 1, 17 pts were in progression, one pt in PR, and another pt in SD at the end of anti-PD-1 therapy alone. In group 1, after anti-PD-1 therapy, the pts were treated with vinblastine (N=3), gemcitabine (N=2) or bendamustine alone (N=3) or in combination with BV (N=4), GVD (N=1), ICE (N=1), DHAP (N=1), escalated BEACOPP (N=1), vinorelbine (N=1), vepeside (N=1) and caelyx (N=1). In group 2, before the combination, the response status was progression for 7 pts and PR for 4 pts. In group 2, to optimize the response to anti-PD-1, pts received vinblastine (N=7), gemcitabine (N=2) and BV (N=2). In the 28 evaluable pts, 11/18 (61%) in group 1 and 9/10 (90%) in group 2 showed an improved response after chemotherapy alone or combination with anti-PD-1 therapy respectively. In group 1, there were 6 CR (32%), 5 PR (26%), 1 SD (5%) and 6 PD (32%) (Figure 1B). In group 2, there were 5 CR (45%), 5 PR (45%) and 1 SD (10%) (Figure 1A). Of note, among the ten pts treated with vinblastine, 4 were in CR, 3 in RP, 1 in SD and 2 in progression. No unexpected toxicity was observed during the CT. Four pts had an allograft after the sequential CT (N=3) and concomitant CT strategy (N=1). Three pts were in CR 274, 279 and 480 days after the allograft and the fourth has not yet been evaluated. Allografts are now scheduled for 6 pts. With a median follow-up of 9.1 months (95%CI, 6.1-14) following the initiation of chemotherapy (alone or combined) the median PFS and OS were 8.4 and 14.6 months, respectively. Conclusions: Our retrospective study showed that pts with an unsatisfactory response or PD with anti-PD-1 therapy had a new objective response with CT alone (61%) or CT in combination with anti-PD-1 therapy (90%). This response could make some pts eligible for allograft. Prospective clinical trials are needed to confirm the synergistic effect of CT with anti-PD-1 therapy and to determine which CT provides the best results in combination with these checkpoint inhibitors. Figure 1 Figure 1. Disclosures Ysebaert: Janssen: Consultancy, Research Funding, Speakers Bureau. Ghesquières: Celgene and Mundipharma: Consultancy, Honoraria; Roche: Research Funding.

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Primary CNS Lymphoma: Updated Results from a Pilot and Phase II Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pilot Trial ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Abstract Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). A 5-year overall survival probability (OS) of 69% could be demonstrated in 30 pts within a phase-II trial on HDT and ASCT with consolidating whole-brain-irradiation (WBRT) (Illerhaus et al. JCO 2006). A subsequent pilot trial on HDT and ASCT without WBRT showed a 5-year OS of 77% (Illerhaus et al. Haematologica 2008). Here we give an update of our two different treatment regimens and future perspectives. Patients and Methods: Thirty pts. ≤65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 3 cycles of high-dose methotrexate (MTX, 8 g/m2), 1 cycle of AraC (2× 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization. Conditioning regimen included BCNU (400 mg/m2) and TT (2×5 mg/kgBW) followed by ASCT. Hyperfractionated WBRT (45 Gy, 2×1Gy/d) was administered as consolidation. In our subsequent pilot trial 13 pts. (age 38–67 years) were treated without consolidating WBRT; CHT was intensified with 4 cycles MTX 8g/m2, 2 cycles AraC (2× 3 g/m2) and TT (40 mg/m2). Dose escalated HDT included BCNU (400 mg/m2) and TT (4×5 mg/kgBW) followed by ASCT. WBRT was reserved for pts. not responding to CHT. Results: Median follow-up of the 30 pts. treated within our phase II trial was extended to 95 months (mo), the updated 5-year OS of all pts. is 66.6% and 82,3% of the subgroup of pts. who underwent HDT and ASCT (n=23), respectively. Three additional deaths occurred due to relapse (n=2) after 45 and 71 mo and due to comorbidity (n=1) after 103 mo. Five of 30 pts. developed severe leukoencephalopathy during follow-up. With a median follow-up of 35 mo in the 13 pts. treated within the pilot-phase without consolidating WBRT 3-year OS of all pts. is 77%. No further relapse or non-relapse mortality occurred in this pilot-group during. Most recent follow-up data will be presented in detail. Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as initial therapy for pts. with PCNSL. The restriction of WBRT to refractory disease shows similar OS rates and a decrease in neurotoxicity. In an ongoing multicenter phase-II trial immunotherapy with rituximab is combined with HDT and ASCT to further increase remission rates. A future randomized trial should be focused on the efficacy of consolidation with HDT supported by ASCT.

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

Prolonged Survival with Low Incidence of CNS Relapse and Late Toxicities in a Retrospective Series of 278 Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma Treated with Intensified Chemotherapy with or without Rituximab At Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1606-1606
Author(s):  
Annalisa Chiappella ◽  
Alessia Castellino ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Andrea Evangelista ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Secondary Malignancies ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Dose Dense

Abstract Abstract 1606 Introduction. Diffuse Large B-cell Lymphoma (DLBCL) patients at high-risk (age-adjusted International Prognostic Index (aa-IPI) 2–3), had a dismal prognosis if treated with conventional chemotherapy. The introduction of intensive regimens and the addition of monoclonal antibody anti-CD20, improved prognosis, but some issues remain unresolved such as: the risk of central nervous system (CNS) relapses and the incidence of late toxicities. We analyzed a series of young DLBCL patients at high-risk consecutively treated in four prospective trials by the Italian Lymphoma Foundation (FIL) with the aim to assess the risk of CNS relapses and late toxicities in this series of patients with a prolonged follow-up Methods. From 1986 to 2006, 278 patients with DLBCL with aa-IPI 2–3 at diagnosis, were enrolled in four consecutive trials previously reported. Thirty-two into a phase II study, treated with 12 weekly infusion of MACOP-B; 39 into a phase II trial with eight weekly MACOP-B infusions followed by high-dose cytarabine, mitoxantrone and dexamethasone (MAD) plus standard BEAM and autologous stem cell transplantation (ASCT); 95 in a phase III trial that randomized high-dose sequential (HDS) chemotherapy plus ASCT (45 patients) vs six courses of dose-dense intensified CHOP (iCHOP) (50 patients); 112 into a phase II trial with four courses of iCHOP in combination with Rituximab followed by Rituximab-MAD + BEAM and ASCT. CNS prophylaxis was not mandatory in the four protocols. Updated data regarding of survival, CNS relapses and late toxicities were recorded on June 2011. Results. Clinical characteristics were: aa-IPI 2 in 55%, aa-IPI 3 in 45%, PS > 2 in 66%, LDH upper normal value in 89%, number of extranodal sites > 2 in 35%, bone marrow involvement in 27% of patients, with no statistical differences between the four trials. With a median follow-up of five years, 5-year Overall Survival (OS) was 63% (95% CI: 57–69%) in the whole series; 5-year OS by treatment was 41% (95%CI: 24–74%) in MACOPB, 54% (95%CI: 37–68%) in MACOPB+MAD+BEAM and ASCT; 53% (95%CI: 38–67%) in HDS+ASCT; 58% (95%CI: 43–70%) in iCHOP; 79% (95%CI: 70–86%) in R-iCHOP+R-MAD+BEAM and ASCT. In a multivariate analysis, the risk of death was significantly reduced in R-iCHOP+R-MAD+BEAM and ASCT (p<.001) and was adversely influenced by age with a progressive increase of five years at diagnosis (p.008) or aa-IPI3 (p.001). Four patients experienced CNS relapses, three of them in R-iCHOP+R-MAD+BEAM and ASCT and one in MACOPB. Only one of the four patients received CNS prophylaxis with intrathecal Methotrexate, even if all of them were at risk for CNS relapse according to Italian Society of Hematology guidelines (Barosi, Hematol 2006). Cumulative incidence of CNS recurrence at 10 years for R-iCHOP+R-MAD+BEAM and ASCT regimen was 3.6% (0 to 7.8). Most frequent late toxicities were dyslipidemia and secondary amenorrhea. Regarding to secondary malignancies, myelodisplasia or acute myeloid leukemia were recorded in three patients, two of them treated with R-iCHOP+R-MAD+BEAM and ASCT, at a median time of seven years off therapy. The actuarial risk of secondary malignancies at 10 years for R-iCHOP+R-MAD+BEAM and ASCT was 4.2% (0 to 10). Conclusions. The addition of Rituximab to dose-dense iCHOP plus high-dose chemotherapy plus BEAM and ASCT improved the outcome in young untreated DLBCL patients at poor prognosis, with an acceptable risk of secondary malignancies and late toxicities. A careful identification of patients at risk could avoid the risk of CNS relapse. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document