Treatment of Progression of Myeloproliferative Disorders(MPD) to MDS/AML by Azacytidine (AZA) : A Preliminary Report on 17 Patients (pts)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2800-2800
Author(s):  
Sylvain Thépot ◽  
Raphael Itzykson ◽  
Emmanuel Raffoux ◽  
Murielle Roussel ◽  
Caroline Dartigeas ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Health Agency ◽  
Early Death ◽  
Jak2 V617f ◽  
Primary Myelofibrosis ◽  
Myeloproliferative Disorders ◽  
Median Number ◽  
Overall Response ◽  
Transfusion Independence

Abstract Background: MDS or AML occurring during the course of MPD carry a very poor prognosis and current treatments, with the exception of allogeneic SCT, have very limited efficacy. AZA significantly improves survival in higher risk MDS (ASH 2007, abstr n° 817) and in some AML, but its use has not been extensively reported so far in MDS and AML post MPD. Methods: The French health agency (AFSSAPS) designed a still ongoing pt named program (ATU) of AZA in higher risk MDS and poor risk AML. 17 pts with MDS or AML post MPD, included in this program in 5 centers (Paris-Avicenne, Paris St Louis, Paris-Cochin, Tours and Toulouse), before April 08 and having completed ≥ 1 cycle of AZA (75 mg/m2/d during 7 days per 28 d cycle) are analysed here. Response was evaluated according to IWG 2006 criteria for MDS and IWG-AML 2003 criteria for AML. Results: median age was 68y (range 38–83), M/F: 7/10. The initial MPD was Polycythemia Vera (PV) in 6 pts, Essential Thrombocytopenia (ET) in 7 pts, primary myelofibrosis (MF) in 2 pts and unclassified in 2 pts. Median interval from diagnosis to progression was 10 years (range 7 months-22 years). 10/16 (62%) pts had JAK2-V617F mutation. Treatment of MPD had consisted of HU in 7 pts, pipobroman in 4 pts, both in 4 pts, imatinib in 1 pt and Interferon Alfa in 1 pt. At the time of inclusion, WHO classification was AML in 8 pts, and MDS in 9 pts (RAEB-2 in 8pts, RAEB-1 in 1pt) Karyotype was normal (n=2), isolated −7/7q- (n=3), isolated del 5q (n=1), + 8 (n=2), isolated −17 (n=1), t[1;7] (n=2), complex (n=3) including −7 (3), −5(2) and +8(1), and a failure (n=3). Before AZA, 2 pts had received intensive chemotherapy (1 CR, 1 failure) followed by allo SCT in 1 of them (who subsequently relapsed). The median number of cycles of AZA administered was 4 (range 1–9). 2 pts received only 1 cycle due to early death (from aspergillosis and unknown cause). The overall response rate (ORR, including CR, PR, CRi) was 10/17 (59%). In the 15 pts who received more than 1 cycle, 4/8 MDS achieved CR (including one cytogenetic CR) and 2/8 achieved PR. RBC and platelet transfusion independence were achieved in 4/8 and 6/8 respectively (resp). In AML, 1/7 pts achieved CR and 3/7 achieved CRi. 2 of the 10 responders relapsed (after 5 and 12 months resp) and the other 8 remained responders after 1+ to 12 + months (median 3.5). 9/10 responders were still alive after 2 to 16 months (median 5.5). Interestingly, in 3 pts with a very long history of MPD (15, 16 and 22 years) treated with HU or pipobroman, who at progression had MDS and cytopenias, response to AZA was associated to recurrence of MPD (2 TE and 1 PV) requiring restart of cytoreductive therapy in 2 of them. Conclusion: 5 AZA gives encouraging results in MDS or AML occurring in the course of MPD with an overall response rate of 59%. An update, with cases recently included in the program, will be presented.

Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2522-2522 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Farhad Ravandi-Kashani ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Optimal Schedule ◽  
Dose Schedule ◽  
Overall Response ◽  
Transfusion Independence ◽  
Secondary Mds ◽  
To Receive

Abstract Background Decitabine (DAC), a hypomethylating agent, has shown activity in MDS. DAC 150 mg/m2 by continuous infusion has been associated with CR rates of 10% to 20%. We investigated optimizing the dose schedule of DAC in MDS. Study Group and Methods Patients (pts) with IPSS intermediate 1–2 & high risk MDS were randomized to one of 3 schedules of DAC: 1) 20 mg/m2 IV over 1 hour daily x 5; 2) 10 mg/m2 IV over 1 hour daily x 10; or 3)10 mg/m2 subcutaneously (SQ) BID x 5. A total of 95 pts are to be treated; Bayesian randomization is implemented based on CR rates. Courses were given every 28 days. Delays to allow counts recovery were permitted every 3 courses, or if myelosuppression without disease, or severe myelosuppression complications. Pts were allowed to receive erythropoietin 40,000 units weekly for anemia, or GCSF if needed. Response criteria for CR & PR were as for AML (PR requiring also ↓ blasts by >50%). Clinical benefit (CB) referred to one or more of: platelets î by ≥ 50% and >30 x 109/L, or granulocytes increase by ≥ 100% and to >109/L, or hemoglobin î by ≥ 2 g/dl or transfusion independence, or splenomegaly ↓ by 50% or more, or monocytes ↓ by 50% or more (pretreatment >5 x 109/L). Results 92 pts have been treated; median age 65 (31–90) yrs; 66% >60 yrs old. IPSS: intermediate-1 25%; intermediate-2 38%; high 19%; CMML 17% Cytogenetic abnormalities 57%; secondary MDS 17%; marrow blasts > 10% in 31%. 27 pts had prior erythropoietin; 17 had prior GCSF; 22 had other prior therapies. Presently, 89 pts have received 1 course. Results: 32 CR (36%); 7 PR (8%); 13 marrow CR + CB (15%); 16 CB (18%); overall response 68/89=76%. Median courses to CR 3 (range 1 to 6). Median follow-up of 9 months; 48 pts continue on DAC. Compared with a 114 pts with MDS who received intensive chemotherapy (2000–2004), CR rate was lower with DAC (36% vs. 45%), overall response rate was favorable; 6-week mortality was lower with DAC (1% vs. 21%); and estimated survival favorable (p = 0.00007). CR rates by schedule: 5 days IV 24/58 (41%); 5 days SQ 4/14 (28%); 10 day IV 4/17 (24%). There was more myelosuppression with 10 day IV. After 55 patients were randomized, the 5 day IV arm was determined statistically superior, therefore, remaining patients were not randomized, but were treated with 5 days IV therapy. Conclusions DAC has significant anti-MDS activity; 2) optimal schedule: 20 mg/m2 IV over 1 hour daily x 5; 3) timely repeated courses needed for optimal response.

A Phase I/II Study of Bortezomib and Low Dose Intravenous Melphalan (BM) for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2555-2555 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Nicola Foot ◽  
Samir Agrawal ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Median Number ◽  
Overall Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background: Bortezomib as a single agent has known efficacy in the treatment of relapsed multiple myeloma. The overall response rate (CR+PR+MR) was 35% in the SUMMIT study and 46% in the APEX study. In-vitro studies including our own have demonstrated potent synergy with other chemotherapeutic agents such as melphalan. It therefore follows that responses to bortezomib may be further improved by the combination of such drugs. Aims: The primary objectives of this Phase I/II study was to assess the safety, tolerability and response rates in patients with relapsed multiple myeloma; secondary objectives being time to progression (TTP) and overall surival (OS). Methods: This was a multi-centre, non-randomised trial for patients with relapsed myeloma. Patients received bortezomib 1.3mg/m2 on days 1,4,8 and 11 of each 28 day cycle with melphalan on day 2 at increasing dose levels. This was initially at 10mg/m2, but due to cytopenias subsequently at 2.5 and 5mg/m2 (levels 1a, 1 and 2) and we plan to escalate to 7.5mg/m2. Up to 8 cycles were given with dexamethasone added for stable or progressive disease after 4 or 2 cycles respectively. Responses were determined by EBMT criteria. Results: To date, 18 patients have been enrolled (12 male 6 female; median age 60 [range 44–73]; median number of prior therapies 3 [range 1–5] of which 17 have had at least one autologous stem cell procedure with high dose melphalan; 10 prior thalidomide and 2 prior bortezomib). 12 patients received melphalan at 10mg/m2 but due to unacceptable delays predominantly due to thrombocytopaenia, subsequent treatment levels commenced at 2.5mg/m2. The median number of cycles completed thus far is 4 (range 0–8) and of the 16 evaluable, the overall response rate (CR+PR+MR) across all treatment levels was 50% rising to 75% following the addition of dexamethasone as per protocol. At level 1a (melphalan 10mg/m2 ,N=12, median number of cycles completed =5) the best responses (with dexamethasone as indicated) were: 1CR, 1 VGPR, 5 PR, 2 MR; at level 1 (melphalan 2.5mg/m2, N=4) 1 PR, 2 MR (after 2 cycles only). The median time to any response was 1 cycle (range 1–3 ). Three patients have progressive disease, but the median TTP and OS have not yet been reached (median follow-up 3 months). Non-haematological toxicities have been modest with 7 SAEs reported of which only 1 was possibly drug related (myocardial infarction), and 4 episodes of Grade 3 neuropathy (2 resulting in study withdrawal). The commonest grade 3–4 haematological toxicity was thrombocytopaenia (N=10) complicated by bleeding in one patient, followed by neutropenia (N=6). Summary: The combination of bortezomib and intravenous melphalan can be given safely to patients with relapsed multiple myeloma and dose escalation is ongoing. Myelosupression was the commonest grade 3–4 adverse event. A response rate of 50% was seen, which was further improved to 75% with the addition of dexamethasone. This combination may therefore result in higher responses than single agent bortezomib in heavily pretreated patients.

Gemcitabine in Combination with Oxaliplatin (GEMOX) As a Salvage Regimen in Patients with Relapsed/Refractory Hodgkin's Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1517-1517 ◽  
Author(s):  
Evren Ozdemir ◽  
Alma Aslan ◽  
Alev Turker ◽  
Ibrahim Barista ◽  
Ayse Kars
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Hodgkin's Lymphoma ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Refractory Disease ◽  
Salvage Regimen ◽  
Overall Response

Abstract This study's objective was to evaluate the efficacy and safety of gemcitabine in combination with oxaliplatin (GEMOX) as a salvage regimen in patients with relapsed or refractory Hodgkin's lymphoma. Twenty-five patients were enrolled. All patients had received ≥ 2 prior chemotherapy regimens, had an ECOG performance status ≤ 2 and had adequate organ function. Patients received intravenous gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) on days 1 and 15, every 4 weeks. The median age was 29 years (range, 18-64) and 16 (68%) were male. Twenty-one (84%) had primary refractory disease (n=13) or relapsed within 12 months after initial therapy (n=8). All had previous platinum-based salvage chemotherapy (ICE, 23; DHAP, 2). Ten patients (40%) had relapsed/refractory disease following autologous stem cell transplantation (SCT). None had previous brentuximab vedotin treatment. Twenty-one (84%) patients were refractory or progressive on the last treatment. Median number of previous lines of chemotherapy was 2 (range, 2-4). Median number of GEMOX cycles administered to the patients was 3 (range, 2-6). Treatment response was evaluated with PET-CT before and 2-3 cycles after treatment, and those patients who demonstrated a response continued to receive a maximum of 6 courses of GEMOX or bridged to SCT. Of 25 patients, 2 (8%) had complete response, 9 (36%) had partial response and the remaining patients had refractory/progressive disease with an overall response rate of 44%. Seven of the 10 patients who had relapsed/refractory disease after autologous SCT achieved a response (CR, 2; PR, 5). The median time to progression for responding patients was 3 months (range, 1-40 months). One patient is disease free for 40 months. Three patients were successfully bridged to SCT (autologous, 2; allogeneic, 1). Main toxicity was hematological. Grade ≥ 3 hematologic toxicity occurred in 10 patients: thrombocytopenia (36%), neutropenia (16%) and anemia (8%). Among these, 7 had previous autologous SCT. One patient had grade 4 neutropenia and thrombocytopenia. Treatment cycle postponed in 6 patients without dose reduction because of hematological toxicity. Seven patients (28%) needed G-CSF support. One patient developed febrile neutropenia. No treatment-related deaths occurred. GEMOX was shown to be an effective salvage regimen in patients with relapsed/refractory Hodgkin's lymphoma, producing an overall response rate of 44%. It is an active regimen in patients who had relapsed/refractory disease after autologous SCT. Although, the median PFS time was short, some patients can be bridged to SCT and some can get long-term PFS. Hematological toxicity was common, especially in patients with previous autologous SCT. Disclosures Off Label Use: Gemcitabine in Hodgkin's Lymphoma Oxaliplatin in Hodgkin's Lymphoma.

A Case Series Of Continuous Low Dose Lenalidomide In Patients With Relapsed Or Refractory Classical Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5134-5134 ◽  
Author(s):  
Ahmed Sawas ◽  
Sean Clark-Garvey ◽  
Ellen Neylon ◽  
Ameet Narwal ◽  
Kathleen Maignan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Dose Reduction ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Classical Hodgkin Lymphoma ◽  
Time To Progression ◽  
Overall Response

Abstract Background Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge with limited effective treatments after high dose therapy with autologous stem cell transplantation (ASCT). Lenalidomide (Revlimid®) is an approved anti-neoplastic therapy for multiple myeloma, mantle cell lymphoma and myelodysplastic syndrome with del(5q). It has emerged as an agent with a manageable toxicity profile and promising clinical activity in a number of B cell malignancies. Two clinical trials have evaluated lenalidomide in rel/ref patients with cHL at a dose of 25mg daily for 21 days of a 28 day cycle. One study reported an overall response rate of 14%, a median time to progression of 3.2 month, with a median number of prior therapies of 2. The second study reported an overall response rate of 19%, a cytostatic response rate (CR+PR+SD> 6 month) of 33%, with a median number of prior therapies of 4. The most common reported grade 3-4 side effects in these studies respectively were: neutropenia 28% and 47%, thrombocytopenia 28% and 27%, and anemia 21% and 27%. We report on our experience in this case series with continuous low dose (10-20mg) lenalidomide in rel/ref cHL patients. Methods Twelve rel/ref cHL patients (pts) who previously underwent (or were not candidates for) ASCT and/or clinical trials were administered a daily dose of lenalidomide. Pts received 10mg and were titrated up to 20mg, if tolerated, with continuous dosing for 30 day cycles. Treatment continued until disease progression or the development of unacceptable adverse event at the lowest administered dose (5mg) of lenalidomide. Results The median age at treatment was 33 (range 24-61) years with 5 females. Median number of prior therapies was 8 (range 3-16). Ten pts had received a prior stem cell transplant (9 ASCT, 1 allogenic, and 1 both ASCT and allogeneic). Of the 12 pts, we observed 3 PR (25%), and 9 SD (8 for more than 6 months) for an overall response rate of 25% and an overall cytostatic response rate (CR+PR+SD> 6 month) of 92%. Median number of cycles received was 6 (range 2-15); six patients remain on therapy. One patient with a PR after 2 cycles of therapy underwent allogeneic stem cell transplant. The median time to progression for the remaining 11 patients was 7.5 months (range 4-15 months). Three patients had progression of disease, all of whom were able to enroll on clinical trials. One patient discontinued therapy because of exacerbation of preexisting neuropathy and was able to transition to chemotherapy. A second patient discontinued therapy after experiencing significant fatigue. In general, the treatment was well tolerated, and the most common clinically significant adverse events were: neutropenia in 4 patients which was managed by GCSF support and dose reduction, exacerbation of neuropathy in 2 patients with one patient discontinuing therapy and dose reduction in the second, and diarrhea in one patient managed with dose reduction. Conclusions Despite a far more heavily treated patient population, continuous, low dose, single agent lenalidomide was both tolerable and effective in patients with rel/ref cHL. Continuous low dose lenalidomide is able to provide meaningful time to progression and bridge to further therapy. A clinical trial to evaluate the efficacy of continuous daily dosing of lenalidomide in rel/ref cHL is warranted. Disclosures: Off Label Use: Lenalidomide in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma. O'Connor:Celgene: Consultancy, Research Funding.

Tipifarnib (ZARNESTRATM in Previously Untreated Poor-Risk AML of the Elderly: Updated Results of a Multicenter Phase 2 Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 874-874 ◽  
Author(s):  
Jeffrey E. Lancet ◽  
Jason Gotlib ◽  
Ivana Gojo ◽  
Eric J. Feldman ◽  
Lawrence Morris ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Hospitalization Rate ◽  
Phase 2 ◽  
Overall Response ◽  
Poor Risk ◽  
Phase 2 Trial ◽  
Multicenter Phase

Abstract Farnesyltransferase inhibitors (FTI) make up a novel class of anti-cancer agents that competitively and selectively inhibit farnesyl protein transferase. Early trials of the orally bioavailable non-peptidomimetic FTI tipifarnib (ZARNESTRATM, Johnson & Johnson PRD) demonstrated both clinical responses and excellent tolerability in patients with poor-risk or refractory acute myeloid leukemia (AML). (Karp, et al. Blood97:3361, 2001). We herein report updated results of a multicenter phase 2 trial of tipifarnib in an elderly, previously untreated poor-risk AML population who refused or were deemed unfit for conventional induction chemotherapy. Tipifarnib was administered orally in the outpatient setting at a dose of 600 mg BID for 21 days, followed by a 1–3 week recovery period. Up to 4 cycles of tipifarnib were permitted in patients with complete responses (CR). The primary endpoint was overall response rate (CR + PR). Secondary endpoints included toxicity rates, measurement of markers of farnesylation (HDJ-2) in bone marrow cells, measurement of signaling intermediates ERK and AKT, and RNA microarray expression patterns. Accrual to the trial is complete. 170 patients have been enrolled, 148 of whom are evaluable for response (AML=160; high-risk MDS=4; high-risk CMML=6). The median age was 73 years (range 34–85), and 76 patients (45%) were age = 75. M/F ratio was 2:1. An unfavorable karyotype and/or antecedent MDS was present in 47% and 79% of patients, respectively. The median number of cycles received was 1, and the median number of days of drug received was 36 days. Dose reductions were implemented in 38% of patients, more commonly in cycles subsequent to cycle #1. The overall response rate (CR + PR) was 34%. CR occurred in 18% of patients. Responses were evenly distributed across study centers. In patients ≥ 75 years, the overall response rate was 30% (CR 20 %). Median CR duration was 6.4 months (range 1.5–11+ months). Median overall survival was 5.6 months for all patients. CR patients had a median survival of 14.4 months, with 63% alive at 12 months. In non-responders, median survival was 3.1 months. The incidence of grade = 3 tipifarnib-related non-hematologic adverse events was 43%, comprised mainly of infectious and gastrointestinal complications. The hospitalization rate for tipifarnib-related toxicity was 18% (median duration: 12 days). The death rate from tipifarnib-related toxicity at 6 weeks was 5%. Microarray analysis of pre-and post-treatment bone marrow samples is being performed to identify both predictive and pharmacodynamic gene markers of response to tipifarnib. In summary, tipifarnib is a novel outpatient treatment with activity in previously untreated poor-risk AML. The low hospitalization rate may reflect the low incidence of severe non-hematological toxicity.

Activity of lenalidomide in a phase II trial for T-cell lymphoma: Report on the first 24 cases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8524-8524
Author(s):  
G. S. Dueck ◽  
N. Chua ◽  
A. Prasad ◽  
D. Stewart ◽  
D. White ◽  
...  
Keyword(s):  
T Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Large Cell ◽  
Median Number ◽  
Clinical Activity ◽  
Cell Transplant ◽  
Overall Response ◽  
T Cell Lymphomas ◽  
Common Grade

8524 Background: Novel therapies are needed to improve outcomes in T-cell lymphomas. We report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas. Methods: Patients with relapsed and refractory T-cell lymphomas other than mycosis fungoides were prescribed oral lenalidomide (25mg daily) on days 1 to 21 of each 28 day cycle, with standardized dose reductions for toxicity. Treatment continued until disease progression, death or unacceptable toxicity. The primary endpoint was overall response rate, and secondary endpoints were complete and partial response rates, progression-free and overall survival (PFS, OS), and safety. The two-stage design allows for up to 40 patients. Results: At the time of this interim analysis, 24 patients were enrolled in this study and 23 were evaluable for response. The median age was 65 years. ECOG PS was 0–1 (n=15), 2 (n=7), 3 (n=2). The histology was peripheral T-cell unspecified (PTCL-u, n=10), angioimmunoblastic (n=7), anaplastic large cell (n=5), enteropathic T-cell (n=1) and hepatosplenic gamma/delta (n=1). Median number of prior therapies was 1 (range, 0–4), and three had prior autologous stem cell transplant. Four patients were previously untreated and not candidates for combination chemotherapy. Median time from completion of prior therapy to the start of lenalidomide was 8 months (range, 1–48 months). The overall response rate was 7/23 (30%); all were partial responses. Two patients had stable disease (SD) for ≥3 cycles. Responses were seen in anaplastic, angioimmunoblastic, and PTCL-u histologies. Median PFS was 96 days (range, 8–696 days). Median OS was 241 days (range, 8–696+ days). Among the 9 patients with SD or better, median PFS was 168 days and median OS has not yet been reached with 241–696 days of follow-up. The most common grade 4 adverse event was thrombocytopenia (33.3%). The most common grade 3 adverse events were neutropenia (20.8%), febrile neutropenia (16.7%), and pain NOS (16.7%). Conclusions: In relapsed and refractory T-cell lymphomas, oral lenalidomide monotherapy has clinical activity and toxicity is consistent with the known profile of lenalidomide. Further study of lenalidomide in these diseases is warranted. [Table: see text]

scholarly journals Efficacy of Lenalidomide plus Low-Dose Dexamethasone in Thai Patients with Relapsed and/or Refractory Multiple Myeloma

2021 ◽  
Vol 73 (5) ◽  
Author(s):  
Chutima Kunacheewa ◽  
Noppadol Siritanaratkul
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Serious Adverse Events ◽  
Refractory Multiple Myeloma ◽  
Overall Response ◽  
Depth Of Response

Objective: Lenalidomide is an immunomodulatory agent with proven efficacy in the treatment of multiple myeloma. In large global clinical studies, lenalidomide plus dexamethasone has demonstrated significant improvements in the overall response rate and overall survival in patients with relapsed and/or refractory multiple myeloma, compared with a placebo and dexamethasone. This is the first study to report lenalidomide plus low-dose dexamethasone administered in Thai patients. Methods: The aim of this phase II, single-center, single-arm study was to evaluate the efficacy and safety of lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. The primary endpoint was the overall response rate at the fourth treatment cycle. Secondary endpoints included depth of response, time to response, and adverse events. Results: In total, 15 patients with a median age of 61 years old (range 23–74 years old) who had received at least one prior anti-myeloma therapy were enrolled in the study and administered 4-week cycles of lenalidomide 25 mg/day (days 1–21) and dexamethasone 40 mg/week. Patients continued in the study until the occurrence of disease progression or serious adverse events. The overall response rate was 86% and 73.3% at the fourth and from all treatment cycles, respectively (median number of treatment cycles, 10.25), and the median dose for patients aged >60 years old was 15 mg/day. The overall response rate at the fourth cycle in patients who had received prior novel agents (bortezomib and/or thalidomide) was 81.82% compared with 100% in those who had received prior conventional therapy (p = 0.15). The most common adverse events reported were anemia and neutropenia, which were both manageable. Conclusion: Lenalidomide and low-dose dexamethasone was highly effective in Thai patients with relapsed and/or refractory multiple myeloma, with a manageable adverse event profile. These findings suggest that lenalidomide 15 mg/day is a safe and effective dose for Thai patients aged ≥60 years old.

Phase II multicenter trial of docetaxel+oxaliplatin in stage IV gastroesophageal and/or stomach cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4071-4071
Author(s):  
D. A. Richards ◽  
L. Wilfong ◽  
D. Reznick ◽  
D. McCollum ◽  
K. A. Boehm ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Safety Profile ◽  
Overall Response Rate ◽  
Response Rate ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Stage Iv ◽  
Median Number ◽  
Overall Response

4071 Background: The treatment of adenocarcinoma of the gastroesophageal junction /stomach (AGEJ/S) remains a therapeutic challenge. This study was conducted to explore the efficacy and safety profile of the combination of docetaxel+oxaliplatin in patients with previously untreated advanced AGEJ/S. Docetaxel has shown significant single-agent activity and has recently been shown to increase response rates and overall survival when combined with cisplatin plus 5-FU. Oxaliplatin is associated with a more favorable safety profile compared to other platinum-based drugs (ie, cisplatin). Methods: Patients with metastatic (Stage IV) AGEJ/S were eligible. Treatment consisted of docetaxel 60 mg/m2 over 1 hour IV followed by oxaliplatin 130 mg/m2 over 2 hours on Day 1 of each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity; primary endpoints are response rate, toxicity, and progression free and overall survival. Results: We have enrolled all planned eligible patients (N = 71). Baseline characteristics include a median age of 59.5 years, 72% male patients, 76% white, and ECOG PS scores 0/1/2 of 45%/49%/6%, respectively. 32.8% of patients had distal gastric cancer (fundus or pylorus). The median number of cycles delivered to date is 6 (range, 1–14). Twenty patients (31%) have required dose reductions primarily due to neutropenia. Grade 3–4 toxicities include neutropenia (69%); vomiting (17%); nausea (16%); dehydration, fatigue, and diarrhea (13%, each), and thrombocytopenia and febrile neutropenia (7%, each). Sixty-six patients have completed ≥2 cycles. The best overall confirmed response rate, by RECIST, was 24 PR (35.6%) for an overall response rate of 35.6%. Median time to response was 2.4 months and median duration of response was 4.1 months. Median survival was 9.2 months and median PFS was 4.4 months. Conclusions: The combination of docetaxel and oxaliplatin is associated with manageable toxicity in this group of patients with AGEJ/S. The best overall response rate of 35% and median survival of 9.2 months is encouraging and comparable to other standard front-line regimens. This research was supported, in part, from a research grant from sanofi-aventis. [Table: see text]

Inotuzumab ozogamycin (I0), a CD22 monoclonal antibody conjugated to calecheamicin, given weekly, for refractory-relapse acute lymphocytic leukemia (R-R ALL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6501-6501
Author(s):  
Elias Jabbour ◽  
Susan Mary O'Brien ◽  
Deborah A. Thomas ◽  
Jeffrey L. Jorgensen ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Median Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Stopping Rules ◽  
Weekly Schedule ◽  
Overall Response ◽  
Frequent Exposure

6501 Background: Patients (pts) with R-R ALL have a poor prognosis. CD22 is highly expressed in ALL. We have previously reported on 49 pts with R-R ALL treated with IO at the dose of 1.8 mg/m2 every 3-4 weeks; the overall response rate was 57%. From preclinical studies, lower dose more frequent exposure schedules to IO may offer better anti-ALL activity. Methods: Pts with R-R ALL received IO 0.8 mg/m2 on Day 1, 0.5 mg/m2 on Day 8, and 0.5 mg/m2 on Day 15. The total dose per course remained the same 1.8 mg/m2. Courses were given every 3-4 weeks. Early stopping rules were implemented for an overall response rate < 40%. Results: 20 pts were treated so far. Median age was 57 yrs (range 22–84). Cytogenetics were: Ph+ in 7 (35%), t(4:11) in 2 (10%) , diploid in 3 (15%), and other in 8 (40%). CD22 was expressed in > 50% blasts in all pts and in > 90% in 14 (70%). Median number of courses so far was 2 (1–4). 9 (45%) pts received IO as salvage 1 (S1), 5 (25%) as salvage 2 (S2), 6 (30%) as salvage 3 (S3). one pt had allo SCT before IO. Median follow-up is 22 weeks (range, 7-43). Overall, 2/20 pts (10%) achieved CR, 6 had CRp (30%), 2 had marrow CR (10%), 8 were resistant, 2 died within 4 wks. Overall, CR+CRp+mCR (OR) was 50%: S1 6/9 (67%); S2 2/5 (40%); S3 2/6 (33%). Of the 10 responders, 7 pts (70%) became MRD negative. There were no clear correlations between OR and pts/ALL characteristics or with CD22 expression vs. < 90%. In 16 pts with evaluable pharmacokinetics studies, the median end of the infusion levels of IO were 117 ng/ml and 77 ng/ml in responders and non-responders, respectively. Median survival was 7+ months. Median OR duration was 5+ months. Median survival in 10 responders has not been reached. Liver function abnormalities (LFA) were noted as IO related in 7 (35%) pts, severe and reversible in 2 (10%). 4 pts were able to proceed to allo SCT (1 in CR, 3 in CRp) after a median of 4 weeks from the last infusion of IO; No cases of veno-occlusive disease were observed. Conclusions: IO given weekly is active in R-R ALL with an OR of 50%. LFAs occur and are reversible. This study of IO weekly schedule is ongoing. IO and chemotherapy combinations are being pursued.

scholarly journals A Combination of Lenalidomide and Rituximab (ReRi) As Salvage Therapy in Elderly Patients Affected By Diffuse Large B Cells (DLBCL) Lymphoma Relapsed and Refractory

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5109-5109 ◽  
Author(s):  
Guido Gini ◽  
Caterina Bocci ◽  
Michela Sampaolo ◽  
Silvia Trappolini ◽  
Sonia Cacciagiù ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Salvage Therapy ◽  
Overall Response Rate ◽  
Response Rate ◽  
Previous Treatment ◽  
The Elderly ◽  
Median Number ◽  
High Rate ◽  
Overall Response

Abstract BACKGROUND The incidence of non Hodgkin's lymphoma (NHL) increases with age, over one third of NHL cases involves elderly patients >70 years of age. As a matter of fact, many elderly patients (pts) are not enrolled in controlled studies because they do not meet the inclusion criteria. This is the reason why the data from trials on elderly cases are not representative for the whole elderly population. Consequently, many of these patients do not benefit of new therapeutic progresses and the treatment is not yet adequate. Moreover in case of relapse, salvage therapy in the elderly is virtually absent, and the prognosis is extremely poor. Lenalidomide is an immunomodulatory drug with anti-angiogenetic and anti-neoplastic action on cancer cells and also has other anti-tumor activity by acting on the neoplastic microenvironment. Both monotherapy and combination of Lenalidomide with rituximab have shown efficacy in terms of overall response rate (ORR, Overall Response Rate) in the setting of salvage therapy in relapsed/refractory DLBCL, with an acceptable rate of hematologic and extra-hematological toxicities PATIENTS AND METHODS In the period 2013-2014 we consecutively treated 12 elderly patients affected by advanced DLBCL relapsed/refractory. Median age at the start of treatment was 79 years (yrs) (62-86), 5 out 12 was over 80 yrs and 4 out 12 over 75 yrs. The median number of previous treatment was 3 (2-4), 3 pts were transplanted and 4 patients was refractory to previous line of therapy. The treatment scheme included at first cycle: Rituximab 375 mg/m2 i.v. days 1, 8, 15, 22, Desametasone 5 mg p.o. days 1, 8, 15, 22 and Lenalidomide 15 mg/die p.o. from day 2 to 22. From the second to the sixth cycle we administered Rituximab 375 mg/m2 i.v. days 1, 14, Lenalidomide 20 mg/die p.o. from day 2 to 22 RESULTS The overall response rate has been 75% (CR,PR,SD), 3 patients out 12 (25%) achieved a CR and 3 PR (25%). The median PFS was 6 months and with a median follow up of 1 year the overall survival is 25%.(fig.1) All deaths are due to lymphoma progression and the 3 patients in CR are still alive in CCR. CONCLUSIONS In this elderly and heavily pretreated group of patients our scheme containing Lenalidomide-Rituximab has shown an high rate of response with a good rate of CR and a promising trend in overall survival. The treatment appears feasible and safe also in this particular group of frail patients and even if we need more data to confirm we think it will be possible to extend this therapy in frail elderly patients in a most precocious line of treatment. Figure 1. Figure 1. Disclosures Offidani: Celgene, Janssen: Honoraria.

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