Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

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.

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Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽

10.1182/blood-2020-143143 ◽

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.

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Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-119991 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18500 ◽

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]

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Bendamustine-Bortezomib-Dexamethasone in Heavily Pretreated Multiple Myeloma: Old PLUS New Drugs in NOVEL Agents' Era

Blood ◽

10.1182/blood-2021-153954 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 5021-5021

Author(s):

Claudio Cerchione ◽

Lucio Catalano ◽

Davide Nappi ◽

Anna Emanuele Pareto ◽

Fabrizio Pane ◽

...

Keyword(s):

Multiple Myeloma ◽

Real Life ◽

New Drugs ◽

Novel Agents ◽

Cell Transplant ◽

Impressive Result ◽

Significant Efficacy ◽

Heavily Pretreated ◽

Grade 3 ◽

D 20

Abstract Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents'era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD) 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. All patients were relapsed and refractory to last therapies received before BVD. Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT, also after failure of novel agents. Disclosures Martinelli: Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Daichii Sankyo: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau.

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

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200507000-00006 ◽

2005 ◽

Vol 15 (4) ◽

pp. 612-617 ◽

Cited By ~ 1

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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Bendamustine-Bortezomib-Dexamethasone (BVD) in Heavily Pretreated Multiple Myeloma: Old/New in NOVEL Agents' Era

Blood ◽

10.1182/blood-2020-143207 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 2-3

Author(s):

Claudio Cerchione ◽

Lucio Catalano ◽

Davide Nappi ◽

Stefano Rocco ◽

Salvatore Palmieri ◽

...

Keyword(s):

Multiple Myeloma ◽

Real Life ◽

Novel Agents ◽

Cell Transplant ◽

Antiemetic Drugs ◽

Impressive Result ◽

Significant Efficacy ◽

Heavily Pretreated ◽

Grade 3 ◽

D 20

Introduction Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Aims Thus, aiming to provide further insights in this field, also in novel agents'era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD). Methods. 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. All patients were relapsed and refractory to last therapies received before BVD. Results Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). Conclusions The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT, also after failure of novel agents. Disclosures Lucchesi: Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria.

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Bendamustine-bortezomib-dexamethasone (BVD) in heavily pretreated multiple myeloma: Old/new in novel agents' era.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20517 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20517-e20517

Author(s):

Claudio Cerchione ◽

Lucio Catalano ◽

Davide Nappi ◽

Anna Emanuele Pareto ◽

Fabrizio Pane ◽

...

Keyword(s):

Multiple Myeloma ◽

Real Life ◽

Novel Agents ◽

Antiemetic Drugs ◽

Impressive Result ◽

Significant Efficacy ◽

Heavily Pretreated ◽

Low Toxicity ◽

Grade 3 ◽

D 20

e20517 Background: Bendamustine is a bifunctional alkylating agent, with low toxicity, proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). In this retrospective study, It has been evaluated efficacy and tolerance of Bendamustine, in combination with bortezomib-dexamethasone (BVD) in patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. A retrospective real-life analysis of patients with rrMM who had been treated with BVD as salvage therapy has been performed. Methods: 56 patients (31 M/25 F), with rrMM, median age at diagnosis 57.3 years (r. 36-82), median age at start of treatment 61.8 years (r.37-83) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously been treated with schedule containing bortezomib and IMIDs, and 30% had also received radiotherapy. 67%of them had undergone at least to a single auSCT. All patients were relapsed and refractory to last therapies received before BVD. Results: Bendamustine was well tolerated, with grade 3 transfusion-dependent anemia in 41% of patients, and 37% grade 3 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, after a median follow-up of 14 months (r.2-36), ORR was 64% (36/56: 4 CR, 7 VGPR, 16 PR, 9 MR) with 8 PD and 12 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Three patients have shown a notable PR after failure of novel agents (i.e. Carfilzomib and Pomalidomide). Median time to response was 1.2 months (r.1-3), median OS from diagnosis was 62.7 months (r.6-151), median OS from start of Bendamustine was 9.8 months (r.2-36). Conclusions: The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT.

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Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.66.130 ◽

2005 ◽

Vol 23 (23) ◽

pp. 5314-5322 ◽

Cited By ~ 347

Author(s):

Stephen Chan ◽

Max E. Scheulen ◽

Stephen Johnston ◽

Klaus Mross ◽

Fatima Cardoso ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Adverse Events ◽

Dose Level ◽

Locally Advanced ◽

Metastatic Breast ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Grade 3 ◽

Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

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Clinical Response in Heavily Pretreated Mycosis Fungoides with Pembrolizumab: A Case Report

Acta Haematologica ◽

10.1159/000518815 ◽

2021 ◽

pp. 1-3

Author(s):

Ginevra Lolli ◽

Beatrice Casadei ◽

Lisa Argnani ◽

Alessandro Pileri ◽

Cinzia Pellegrini ◽

...

Keyword(s):

Mycosis Fungoides ◽

Assessment Tool ◽

Therapeutic Option ◽

Rapid Responses ◽

Duration Of Response ◽

Heavily Pretreated ◽

Stage Ia ◽

Pretreated Patients ◽

Grade 3 ◽

The Moment

Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.

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CTIM-32. IMMUNE CHECKPOINT INHIBITOR NIVOLUMAB IN PEOPLE WITH RECURRENT SELECT RARE CNS CANCERS: RESULTS OF INTERIM ANALYSIS IN A HEAVILY PRETREATED COHORT

Neuro-Oncology ◽

10.1093/neuonc/noab196.224 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi57-vi58

Author(s):

Marta Penas-Prado ◽

Ying Yuan ◽

Kathleen Wall ◽

Elizabeth Vera ◽

Ukeme Ikiddeh-Barnes ◽

...

Keyword(s):

Safety Profile ◽

Interim Analysis ◽

Cns Tumors ◽

Myxopapillary Ependymoma ◽

Investigational Drugs ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Grade 3 ◽

Total Accrual ◽

Immune Profiling

Abstract INTRODUCTION Standard and experimental therapies for patients with rare CNS tumors are scarce. Nivolumab (PD-1 inhibitor) is approved for several non-CNS cancers. This ongoing Phase II trial (NCT03173950) will determine the efficacy of nivolumab in adults with recurrence/progression of one of 11 selected rare primary CNS tumors. Efficacy is measured by Disease Control Rate (DCR; confirmed CR/PR or durable SD for ≥ 6 months) in 2 cohorts: heavily and non-heavily pretreated patients (heavily pretreated: ≥ 3 prior therapies; non-heavily pretreated: ≤ 2). We report efficacy and safety results of a preplanned interim analysis in the heavily pretreated cohort. METHODS Eligibility includes recurrence/progression of an eligible tumor; age ≥ 18 years; tumor tissue available for histopathology, molecular and immune profiling; KPS ≥ 70; and no steroids at study entry. A total of 150 evaluable patients will be enrolled (75 to each cohort). Prior therapies include radiation and/or standard or investigational drugs. Nivolumab treatment is 240 mg IV every 2 weeks (4 doses); then 480 mg every 4 weeks (14 additional doses). Interim analysis was planned when sample size reached 32 in each cohort. RESULTS As of March 10, 2021, DCR exceeded the minimum required for interim analysis in the heavily pretreated cohort. Among 30 patients, 4 achieved SD > 6 months (medulloblastoma, anaplastic ependymoma, myxopapillary ependymoma, metastatic atypical meningioma). Safety profile (related AEs): grade 3 = 7; grade 4 = 1. Most frequent grade 3-5 AEs regardless of attribution: tumor progression (6); anemia, hydrocephalus, lymphopenia (3 each); cerebral edema, headache (2 each). CONCLUSION DCR exceeded the “go” boundary (i.e., > 2) in the heavily pretreated cohort. Nivolumab showed safety profile consistent with other studies. This cohort will continue to stage 2 and complete total accrual of 75 patients. The trial is currently being expanded to 10 additional sites across the BTTC/NCI-CONNECT consortium.

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