Retrospective review of DPACE therapy for aggressive, refractory multiple myeloma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18500-18500
Author(s):  
A. S. Gerrie ◽  
W. Xu ◽  
S. Fung ◽  
A. K. Stewart ◽  
D. Reece ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Leptomeningeal Disease ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Bridge To Transplant ◽  
Neutropenic Sepsis ◽  
Definitive Therapy ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Gi Bleed

18500 Background: Oral dexamethasone ± thalidomide with a 4-day infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide (DPACE) is an effective induction therapy prior to transplant in patients (pts) with MM. Limited experience also suggests DPACE may reduce disease burden as a salvage regimen for aggressive, refractory MM. Methods: We performed a retrospective review from 1999- 2005 of all MM pts who received DPACE ± thalidomide as a salvage regimen at our center. Results: A total of 39 pts received DPACE at a median 23 mos from diagnosis (range, 10–84). Median age was 53 years (34–70), 51% stage 3 at diagnosis. Plasma cell leukemia had developed in 12 pts and leptomeningeal disease in 4 pts at time of DPACE. Ten of 24 pts (42%) with cytogenetics had del 13q. Pts were heavily pretreated (median 3 prior regimens; prior autotransplant [ASCT] 38%; thalidomide 64%; and bortezomib 10%). Pts received 1–4 cycles as tolerated for refractory (83%) or relapsed (17%) disease. Thalidomide was used in 41% of cycles. Hematologic toxicity was common (grade 3–4 neutropenia 92% and thrombocytopenia 72%). Although G-CSF was used in 71% of cycles, febrile neutropenia was common (53%) and 26% required hospitalization. Overall RR was 36% (14 pts: PR 12, VGPR 2). An additional 8% achieved MR, 23% SD. PD occurred in 15% and 18% died on therapy (4 progressive MM; 2 neutropenic sepsis, 1 GI bleed). No prior ASCT (p=0.04) and <4 prior regimens (p=0.04) predicted for response to DPACE. Eleven pts proceeded to ASCT and one pt to a clinical trial with lenalidomide with a median OS from DPACE of 24.7 mos (95% CI, 11.2–63.6). Those who did not bridge to transplant or trial (n=27) had a short median PFS of 3.0 months (95% CI, 1.2–5.5) and OS of 6.7 mos (95% CI, 1.8–9.7). OS for all 39 pts was 8.7 mos (95% CI, 6.4–12.4). Conclusion: DPACE may be effective salvage therapy for heavily pretreated MM pts. Although the RR of 36% in this poor prognosis cohort is reasonable, the PFS is short and suggests that the best role for this regimen is in bridging to more definitive therapy such as transplantation. [Table: see text]

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Gerardo Musuraca ◽  
...  
Keyword(s):  
Oral Administration ◽  
Oral Treatment ◽  
Novel Agents ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Background Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. Aims In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. Methods 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Results Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Conclusions Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Lucchesi: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5022-5022
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Fabrizio Pane ◽  
...  
Keyword(s):  
Oral Administration ◽  
Oral Treatment ◽  
Novel Agents ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Abstract Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Martinelli: Stemline Therapeutics: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Daichii Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Astellas: Consultancy, Speakers Bureau.

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5648-5648
Author(s):  
Claudio Cerchione ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Fabrizio Pane ◽  
Lucio Catalano
Keyword(s):  
Oral Administration ◽  
Conflicts Of Interest ◽  
Oral Treatment ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Abstract Background: Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. Aims: In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. Methods: 33 patients (19 M/14 F), with rrMM, median age at diagnosis 69 years (r. 52-84), and median age at start of treatment 76 years (r.56-89) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic was evaluable in 14 patients, and in particular three del13q and one t(11;14) were present. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 60% (20/33) of them had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Results: Pomalidomide was well tolerated, with grade 3 anemia in 51% (17/33) of patients, 36.3% (12/33) grade 3 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 30.3% (10/33) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 45.4% (15/33: 4 CR, 5 VGPR, 6 PR), but, considering that we are evaluating a cohort of heavily pretreated patients without any other alternative treatment, with really poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 78.7% (26/33: 4 CR, 5 VGPR, 6 PR, 11 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 92 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Conclusions: Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources. Disclosures No relevant conflicts of interest to declare.

A retrospective study of efficacy and safety of mechlorethamine, vindesine, liposomal doxorubicin, and prednisone (MODP) in relapsed/refractory classical Hodgkin lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19516-e19516
Author(s):  
Min-Hang Zhou ◽  
Chunmeng Wang ◽  
Yang Liu ◽  
Wenjing Ku ◽  
Qingming Yang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Liposomal Doxorubicin ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Brentuximab Vedotin ◽  
Combination Regimen ◽  
Salvage Regimen ◽  
Heavily Pretreated ◽  
Grade 3

e19516 Background: There are few optimized therapeutic options for relapsed and/or refractory classic Hodgkin’s lymphoma (r/rCHL), especially in patients who failed in treatments of autologous stem cell transplantation (ASCT), brentuximab vedotin or even immune checkpoint blockage. Therefore, we developed a chemotherapeutic scheme to evaluate the efficacy in r/rCHL patients with previous various lines of therapies. Methods: Between January, 2014 and December, 2019, a retrospective study was performed on r/rCHL patients from Chinese PLA general hospital who were treated with MOAP regimen consisting of mechlorethamine 6mg/m2, vindesine 4mg, liposomal doxorubicin 15mg/m2 on days 1 and 8, prednisone 1mg/kg per day on days 1 to 10 (MOAP) every 4 weeks. CT or PET/CT were done every two cycles to assess the response. Patients treated with MOAP regimen and complete clinical data were included. Patients with less than two cycles of MOAT or unavailable response assessment were excluded. The primary endpoint were complete remission (CR) and progression-free survival (PFS). Results: A total of 87 patients were included and five patients were excluded, so 82 patients were eligible in the study. The median previous lines and cycles of chemotherapy was 2 (range, 1-7), and 9 (range, 3-31), respectively. All the eligible patients received MOAP regimen for a median 4 cycles (range from 2 to 8), and overall response rate (ORR) was 87.8% including 40 patients in CR (48.8%) and 32 in PR (39.0%). In patients with ≥ 3 lines or ≥ 10 cycles of chemotherapy, up to 50.0% and 41.0% of patients achieved CR, respectively. In patients with previous ASCT, 31.6% of patients also achieved CR. Patients with previous checkpoint inhibitors had even higher CR than those without checkpoint inhibitors, though not significantly (51.6% vs. 47.1%, p = 0.689). Median PFS in patients with CR, PR and SD/PD were 43.8 months, 9.6 months and 6.1 months, respectively (p = 0.000).Patients with < 3 previous lines of chemotherapy had a favorable PFS than those with ≥ 3 previous lines (not reached vs. 14.4 months, (p = 0.032). No differences in PFS were observed in terms of previous cycles of chemotherapy, ASCT and checkpoint inhibitors. Grade ≥ 3 adverse events included 37 leukopenia (45.1%), 16 lung infection (19.5%), 11 anemia (13.4%), 4 thrombocytopenia (4.9%), 3 febrile neutropenia (3.7%) and 3 increased transaminase (3.7%). Conclusions: The MOAP combination regimen produced a favorable CR in r/rCHL failing or progressing on ASCT, checkpoint inhibitors, multiple cycles or lines of chemotherapies. It is an effective salvage regimen in heavily pretreated r/r CHL.

Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory neuroblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22009-e22009
Author(s):  
Jia Zhu ◽  
Zijun Zhen ◽  
Juan Wang ◽  
Tingting Chen ◽  
Suying Lu ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Salvage Regimen ◽  
Brain Involvement ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Grade Iii

e22009 Background: The combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed or refractory neuroblastoma (NB). Methods: Forty-six patients with relapsed or refractory NB were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2 /day i.v. days 1–5) and temozolomide (100 mg/m2 /day p.o. days 1–5) (VIT) during the period 2011–2019. All toxicities were documented. Results: A total of 251 cycles (median 6 cycles/patient) were administered. A complete response (CR) was achieved in 5 patients, partial response (PR) in 27 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 6 patients, with an overall objective response rate (CR+PR) of 69.6%. Eighteen patients developed diarrhea with Grade III or less. Grade 1-2 hematologic toxicity occurred in 10 patients. Grade 3-4 hematologic toxicity developed in 32 patients. VIT was an effective regimen for different metastatic sites. Overall objective response rates to VIT combination for patients with mediastinum, bone marrow/bone, lymph node, abdomen and brain involvement were 100.0%, 80.0%, 77.8%, 50.0%, 42.9%, respectively. UGT1A*28 genotyping performed in 7 patients revealed wild type. Diarrhea occurred in 4 of them. Conclusions: The shorter, 5-day VIT regimen is an active and well-tolerated salvage regimen in relapse/refractory NB.[Table: see text]

Salvage Therapy with Intravenous Liposomal Adryamicin (A), Bortezomib (B), Cyclophosphamide (C), and Dexamethasone (D) (ABCD) in Previously Treated Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2779-2779
Author(s):  
Francesco Di Raimondo ◽  
Alessandra Romano ◽  
Ausilia Gorgone ◽  
Annalisa Chiarenza ◽  
Maide Cavalli ◽  
...  
Keyword(s):  
Partial Remission ◽  
M Protein ◽  
Hematological Toxicity ◽  
P Value ◽  
Hematologic Toxicity ◽  
Prognostic Features ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
Grade 3

Abstract Background: Bortezomib is one of the most active drugs for the treatment of multiple myeloma and there are evidences that its activity is highly increased when it is used in combination with other drugs. We have already reported the activity of Bortezomib in combination with intravenous Melphalan (5 mg/m2) and Dexamethasone (BMD) in relapsed/refractory myeloma patients (ASH 2007, #2728). However, this scheme resulted in an elevated percentage of haematologic toxicity that prompted us to test the combination of Bortezomib with other less myelotoxic but active drugs such as Cyclophosphamide, and a liposomal Adryamicin. Methods: Bortezomib was given at dosage 1.3 mg/m2, and Dexamethasone 40 mg i.v. on days 1, 4, 8, 15 plus liposomal Adryamicin 20 mg i.v. on days 1 and 15, and Cyclophosphamide 100 mg per os for 15 days (1à15). An antibiotic and antiviral prophilaxis was guaranted to all patients with Bactrim and Acyclovir, and EPO and G-CSF were used as recommended. So far, 17 previously treated patients have been enrolled in this study, 4 males and 13 females. Median age was 63 (range 51–78), 7/17 patients were IIIA stage according to Durie and Salmon classification and 3/17 had extra-medullary disease. Five patients were resistant to previous therapies and 10 were relapsed. All patients had been already treated with a median of 2 previous lines of treatment (range 1–6). Four patients were in relapse within 12 months of stem-cell transplantation and 12 patients had already received Bortezomib alone or in combination. Six patients had been already treated with BMD (three were refractory, one in partial remission, and two relapsed) Results: After a median follow up of 5 months (range 1–8) 15/17 were valuable for response since they have received at least 2 cycles of therapy. 6/15 (40%) patients were considered responder: 3 patients had a very good partial remission (M-protein ≤ 90%), 3 patients a partial remission (M-protein &gt;50%), 1 progressed, and 8 were in stable disease according to International Myeloma Working Group Criteria. Side effects were predictable and manageable; the most common grade 3/4 adverse events included hematologic toxicity (thrombocytopenia [18%], neutropenia [6%], anemia [6%]), paresthesia grade 2 in 3 patients and nausea and vomiting grade 3 in only one patient. So far, 1 patient has stopped treatment for progression disease, and only one for toxicity (infectious disease grade III), in both cases after 2courses. In table 1 the comparison of efficacy and toxicity between ABCD and BMD after 3 cycles is reported. ABCD seems to be as effective as BMD (considering that 1/3 of patients had been already treated with BMD) but with higher tolerability. Conclusion: The combination of liposomal Adryamicin, Bortezomib, Cyclophosphamide, and Dexamethasone (ABCD) is effective and well tolerated treatment even for heavily pretreated patients with poor prognostic features. The dosage of some drugs could be increased in order to maximize the overall response rate. BMD % ABCD % p - value * only 1 patient grade 4 TOXICITY #evaluable cycles 152 100 57 100 witheld or deferred cycles 25 16 2 4 0,03 Hematological toxicity grade 3–4 53 35 8* 14 0,005 Extrahematol toxicity grade 3–4 8 5 8* 14 0,05 of pts w RBC transf 16 11 1 2 0,07 of pts w PLT transf 12 8 1 2 0,2 of pts w G-CSF 41 27 1 2 0,0001 stop Tx for toxicity 6 4 1 2 0,28 stop Tx for progression 1 0,6 1 2 0,89 RESPONSE Tot pts 34 100 15 100 PD 3 9 1 7 0,74 SD 15 44 8 53 0,78 PR 7 20 3 20 0,69 VGPR 6 18 3 20 0,81 CR 3 9 0 0 0,57

Phase II Trial of Bortezomib Combined with Weekly Doxorubicin and Oral Dexamethasone for Relapsed or Refractory Multiple Myeloma (MM): Effect of NF-κB Activation on Response.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3545-3545
Author(s):  
Natalie S. Callander ◽  
Shigeki Miyamoto ◽  
Brad Kahl ◽  
Stephanie Markovina ◽  
Martha Raschko ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stromal Cells ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Mobility Shift ◽  
Salvage Regimen ◽  
Cell Extracts ◽  
Grade 3 ◽  
Rpmi 8226

Abstract Despite new therapies, patients with MM continue to relapse. Resistant MM cells are known to possess enhanced NF-κB activity which can be partially overcome in vitro by the proteosome inhibitor bortezomib. Bortezomib can also ameliorate topoisomerase IIαinhibition and restore sensitivity to agents such as doxorubicin. We designed a phase II trial of bortezomib combined with doxorubicin and dexamethasone to exploit this interaction. We also studied NF-κB activation induced by stromal cells and in primary MM cells derived from subjects. Eligibility: Progressive or refractory secretory MM, ≥ 1 previous treatments, total previous doxorubicin ≤ 220 mg/m2; previous bortezomib, transplantation, renal insufficiency with creatinine <5 mg/dl, were allowed. Methods: Patients received bortezomib 1.3 mg/m2 IV days 1,4,8, 11; doxorubicin 15 mg/m2 IV d 1,8 and dexamethasone 20 mg orally on d 1,4,8,11. Cycles were repeated every 21 days up to a maximum of 8 cycles. NF-κB activity was assayed by electrophoretic mobility shift assay using a P32labelled DNA probe on whole cell extracts derived from CD-138 positive cells isolated from pretreatment bone marrow aspirates. For stromal cell studies, CD-138 negative cells were plated, incubated for 14 days and washed. Residual adherent fibroblast like cells were then cocultured with RPMI 8226 MM cells for 24 hours and NF-κB activation in these cells analyzed as described above. Results: 9 patients have been enrolled; 7 patients are assessable for response. Previous treatments included 2 lenalidomide failures, 2 bortezomib failures, 2 transplant failures 1 subject with plasma cell leukemia. Median number of previous regimens: two (range 1–5), age range 40–88. Six of seven (85%) responded with 1 CR, 2 near CR, and 3 partial responses, including both lenalidomide failures. One patient, who had failed all previous therapy, rapidly progressed after one cycle. Of note, MM cells isolated from this resistant patient showed the highest levels of constitutive NF-κB activity whereas MM cells from responding patients showed far less constitutive activity. Stromal cells isolated from other patients demonstrated the ability to induce NF-κB activation in RPMI 8226 cells. Toxicities: no grade 3 hematologic toxicity was observed; 1 patient experienced grade 3 neuropathy, 2 patients grade 2 neuropathy after 6 cycles requiring dose reductions of bortezomib. Cost of doxorubicin $184/cycle (versus $8884/cycle if liposomal doxorubicin substituted). Conclusions: Bortezomib/doxorubicin/dexamethasone is an active, cost effective salvage regimen even in patients failing lenalidomide and single agent bortezomib. Neuropathy was the dose limiting toxicity of this regimen. High levels of constitutive NF-κB may predict for resistance to this regimen and may imply a proteosome independent pathway for NF-κB activation. Further analysis of constitutive NF-κB activity of primary MM and stromal cells in comparison to response is planned.

A dose dense low toxicity salvage regimen for histologically aggressive non-Hodgkin’s lymphoma (NHL): Gemcitabine, rituximab, oxaliplatin combination (GROC) plus pegfilgrastim

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17513-17513 ◽  
Author(s):  
F. Cabanillas ◽  
I. Liboy ◽  
E. Rodriguez-Monge ◽  
O. Pavia ◽  
N. Robles ◽  
...  
Keyword(s):  
Phase I ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Salvage Regimen ◽  
Prognostic Features ◽  
Grade 3 ◽  
Dose Dense ◽  
High Beta

17513 High dose chemo/autologous stem cell transplant (ASCT) is standard treatment for relapsed aggressive NHL. However many are unable to receive ASCT because they are refractory to salvage therapy, too old or too sick. More effective, less toxic salvage regimens are needed prior to ASCT. Gemcitabine (G) and Oxaliplatin (O) are active agents in NHL and exhibit synergism so their combination is attractive to explore together with Rituximab (R). We hereby report the results of a phase I-II trial designed to explore the GROC regimen administered every 14 days with Pegfilgrastim support. After the first 6 pts were entered, the phase I portion was completed; recommended dose: R = 375 mg/m2 on day 1, G = 1,250 mg/M2 on day 2, O = 100 mg/m2 on day 2 and Neulasta 6 mg day 3. So far we have entered 21 pts of which 19 are currently evaluable. Median age = 58 (range = 27–88); 9 were refractory to 1st line therapy, 5 were on 1st relapse, 3 on 2nd and 2 >2 relapses, 12 had high LDH, 10 high Beta-2-M. Using IWG/PET criteria ORR = 79%, CR = 42%, PR = 37%. There was a correlation between response to preceding chemo regimen and response to GROC ( table ). In 6 the response to GROC was better than to preceding regimen while only in 2 was the response worse. At 1 year the projected OS is 49% and PFS 34%. So far, only 5 of 15 responders have relapsed. An intriguing finding is that in 6 of 15 responders, PFS has been longer with GROC than with preceding regimen and shorter in only 1. Grade 4 hematologic toxicity occurred only once. No neutropenic fevers seen. Most common toxicity was reversible transaminitis in 13 (grade 1–2 in 10, grade 3 in 3), neuropathy in 9 (grade 1–2 in 8, grade 3 in 1), diarrhea in 3 (grade 4 in 1). We could deliver courses at a median interval of 14 days. Conclusions: 1- GROC is an effective dose dense salvage regimen. 2- It appears effective even in pts with poor prognostic features including primary refractory disease. 3-Hematologic toxicity is very low and non-hematologic toxicity acceptable. [Table: see text] [Table: see text]

Phase I trial of temsirolimus and lenalidomide in pts with rel/ref lymphomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8075-8075
Author(s):  
Sonali M. Smith ◽  
Kenneth Stuart Cohen ◽  
Justin Paul Kline ◽  
Jose D Zavala ◽  
Kathy Conner ◽  
...  
Keyword(s):  
Phase I ◽  
Response Duration ◽  
Hepatic Function ◽  
Hematologic Toxicity ◽  
Rapid Disease Progression ◽  
Pretreated Group ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity

8075 Background: The PI3K/Akt/mTOR axis is deregulated in lymphomas and is an emerging therapeutic target. We previously reported activity of temsirolimus (TEM) in DLBCL and FL (JCO 2010 28(31); however, the response duration was short. Lenalidomide (LEN) is an immunomodulatory agent with multiple anti-tumoral and microenvironmental effects, with activity across lymphoma subtypes. We are thus conducting a phase I/II study of TEM plus escalating doses of LEN. The phase I portion is completed. Methods: Patients (pts) had rel/ref lymphoma after >1 cytotoxic regimen. Other criteria: ANC > 1000/mL, platelets > 75,000/mL, nl renal and hepatic function, no VTE within 3 months, non-pregnant. A standard “3 + 3” design was used with dose levels (DL) listed (Table). TEM was given IV weekly and LEN was dosed orally on D1-D21, q28 days. Dose-limiting toxicity (DLT) was defined as cycle 1 grade 3 or 4 non-hematologic toxicity not responsive to standard supportive care, grade 4 thrombocytopenia > 7 days (or associated with bleeding or requiring more than 1 platelet transfusion), ANC < 500/mL > 7 days despite growth factors, or any thromboembolic event. Results: 18 pts (13M, 5F), med age 64 y (range, 42-80 y) were enrolled. 3 pts are ineval for DLT evaluation: one withdrew consent before starting treatment, 1 withdrew consent after a single dose, and 1 died of rapid disease progression after 1 dose. There was 1 DLT at DL1 and 2 DLTs at DL3 (Table). Adverse effects that did not meet DLT criteria: hypokalemia, hypertriglyceridemia, vomiting, urinary tract infection, skin infection, nausea, hypoxia, hyponatremia, diarrhea, and hyperglycemia (each occurring in one pt). There are 5 partial responses, 4 stable disease, 3 progressive disease, 2 not adequately assessed, and 4 still on active treatment. Conclusions: The combination of weekly intravenous TEM plus oral LEN is well-tolerated in a heavily pretreated group of pts with rel/ref lymphomas. The recommended phase II doses are TEM 25mg weekly plus LEN 20mg (D1-D21, q28d). [Table: see text]

Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma

2005 ◽  
Vol 15 (4) ◽  
pp. 612-617 ◽  
Author(s):  
B. Piura ◽  
A. Rabinovich
Keyword(s):  
Partial Response ◽  
Fallopian Tube ◽  
Dose Intensity ◽  
Complete Response ◽  
Ca 125 ◽  
Hematologic Toxicity ◽  
Fallopian Tube Carcinoma ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Topotecan has demonstrated antitumor activity in heavily pretreated patients with ovarian carcinoma. This report examines the activity and toxicity of topotecan in 29 heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma. Topotecan 1.5 mg/m2 was administered intravenously on days 1–5, every 21 days. It was second-line chemotherapy in 6 (20.7%) patients, third-line in 15 (51.7%), fourth-line in 4 (13.8%), fifth-line in 3 (10.3%), and seventh-line in 1 (3.4%). Median dose intensity was 1.667 mg/m2/week, and median relative dose intensity was 0.67. Disease complete response was observed in 5 (17.2%) patients, partial response in 1 (3.4%), stable disease in 12 (41.4%), and progressive disease in 11 (37.9%). CA-125 complete response was observed in 3 (10.3%) patients, partial response in 11 (37.9%), stable level in 5 (17.2%), and progressive level in 9 (31%), and no data were available in 1 (3.4%) patient. Toxicity was mainly hematologic: grade 3–4 neutropenia was observed in 20 (69%) patients, grade 3–4 leukopenia in 12 (41.4%), grade 3–4 thrombocytopenia in 9 (31%), and grade 3–4 anemia in 2 (6.9%). It is concluded that topotecan has considerable activity and noncumulative hematologic toxicity in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma.

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