PHASE 1/2 TRIAL OF LENALIDOMIDE IN COMBINATION WITH CYCLOPHOSPHAMIDE AND PREDNISONE (REP) IN PATIENTS WITH LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA (REPEAT-STUDY)
(Abstract release date: 05/19/16)
EHA Library. van der Wagen L. 06/09/16; 132832; E1283
Mrs. Lotte van der Wagen
Contributions
Contributions
Abstract
Abstract: E1283
Type: Eposter Presentation
Background
The outcome of lenalidomide- and bortezomib-refractory multiple myeloma (MM) patients is very poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months. Therefore new treatment modalities are urgently needed. In this respect, several new drugs have recently been approved for the treatment of double refractory MM (such as pomalidomide, carfilzomib, and daratumumab). However, next to the development of new drugs, also the strategy of combining drugs with synergistic activity may result in significant clinical benefit for patients with advanced myeloma.Lenalidomide has well-described immunomodulatory effects, even in the setting of lenalidomide-refractory disease. Similarly, administration of continuous low-dose cyclophosphamide (metronomically dosed) has direct anti-tumor activity, as well as several well-characterized immunomodulatory effects. We have previously shown in a retrospective study that lenalidomide combined with continuous low-dose oral cyclophosphamide (endoxan) and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients.
Aims
To further evaluate this combination, we initiated a prospective phase I/II study to determine the optimal dosing schedule of lenalidomide, low-dose oral cyclophosphamide and prednisone, and to assess its efficacy and safety in lenalidomide-refractory MM patients.
Methods
82 lenalidomide-refractory MM patients were included in this trial; 21 were included in the phase 1 dose-finding part with a classic 3+3 dose-escalation design (5 dose-levels) and 61 patients were included in the phase II part of this trial in which all patients were treated at the maximum tolerated dose (MTD).
Results
The median age of the 82 patients in this phase I/II trial was 66 years (range 41-82); 71% were male. The median duration from diagnosis was 48 months (range 5-169), median number of prior therapies was 3 (range 1-6), and 50 patients (61%) had previously received autologous SCT. All patients were lenalidomide-refractory, 71 (87%) had prior bortezomib treatment, and 54 (66%) had both lenalidomide- and bortezomib-refractory MM. 41% of the patients had high-risk cytogenetic abnormalities as determined by FISH.The MTD was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous oral cyclophosphamide (50 mg/day) and prednisone (20 mg/day). Sixty-seven patients were treated at the MTD (6 in dose-level 4 of phase I and 61 in phase II part of the study). Forty-four of these patients (67%) achieved a partial response or better, including 12 patients (18.2%) with a very good partial response and 3 (4.5%) with a complete remission. Eleven patients (16%) achieved a minimal response, translating to an overall 83% clinical benefit rate. After a median follow-up of 24.5 months median PFS and OS were 12.1 and 29.0 months respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities. At the MTD, neutropenia (22%) and thrombocytopenia (22%) were the most common grade ≥3 hematological adverse events. Infections (21%) were the most common grade ≥3 non-hematological adverse events.
Conclusion
REP is a well-tolerated regimen and induces a high response rate with prolonged PFS and OS in lenalidomide-refractory MM patients. REP should be considered a valuable salvage option for lenalidomide-refractory MM patients.This trial was registered at www.clinicaltrials.gov as #NCT01352338.
Session topic: E-poster
Keyword(s): Multiple myeloma, Refractory
Type: Eposter Presentation
Background
The outcome of lenalidomide- and bortezomib-refractory multiple myeloma (MM) patients is very poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months. Therefore new treatment modalities are urgently needed. In this respect, several new drugs have recently been approved for the treatment of double refractory MM (such as pomalidomide, carfilzomib, and daratumumab). However, next to the development of new drugs, also the strategy of combining drugs with synergistic activity may result in significant clinical benefit for patients with advanced myeloma.Lenalidomide has well-described immunomodulatory effects, even in the setting of lenalidomide-refractory disease. Similarly, administration of continuous low-dose cyclophosphamide (metronomically dosed) has direct anti-tumor activity, as well as several well-characterized immunomodulatory effects. We have previously shown in a retrospective study that lenalidomide combined with continuous low-dose oral cyclophosphamide (endoxan) and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients.
Aims
To further evaluate this combination, we initiated a prospective phase I/II study to determine the optimal dosing schedule of lenalidomide, low-dose oral cyclophosphamide and prednisone, and to assess its efficacy and safety in lenalidomide-refractory MM patients.
Methods
82 lenalidomide-refractory MM patients were included in this trial; 21 were included in the phase 1 dose-finding part with a classic 3+3 dose-escalation design (5 dose-levels) and 61 patients were included in the phase II part of this trial in which all patients were treated at the maximum tolerated dose (MTD).
Results
The median age of the 82 patients in this phase I/II trial was 66 years (range 41-82); 71% were male. The median duration from diagnosis was 48 months (range 5-169), median number of prior therapies was 3 (range 1-6), and 50 patients (61%) had previously received autologous SCT. All patients were lenalidomide-refractory, 71 (87%) had prior bortezomib treatment, and 54 (66%) had both lenalidomide- and bortezomib-refractory MM. 41% of the patients had high-risk cytogenetic abnormalities as determined by FISH.The MTD was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous oral cyclophosphamide (50 mg/day) and prednisone (20 mg/day). Sixty-seven patients were treated at the MTD (6 in dose-level 4 of phase I and 61 in phase II part of the study). Forty-four of these patients (67%) achieved a partial response or better, including 12 patients (18.2%) with a very good partial response and 3 (4.5%) with a complete remission. Eleven patients (16%) achieved a minimal response, translating to an overall 83% clinical benefit rate. After a median follow-up of 24.5 months median PFS and OS were 12.1 and 29.0 months respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities. At the MTD, neutropenia (22%) and thrombocytopenia (22%) were the most common grade ≥3 hematological adverse events. Infections (21%) were the most common grade ≥3 non-hematological adverse events.
Conclusion
REP is a well-tolerated regimen and induces a high response rate with prolonged PFS and OS in lenalidomide-refractory MM patients. REP should be considered a valuable salvage option for lenalidomide-refractory MM patients.This trial was registered at www.clinicaltrials.gov as #NCT01352338.
Session topic: E-poster
Keyword(s): Multiple myeloma, Refractory
Abstract: E1283
Type: Eposter Presentation
Background
The outcome of lenalidomide- and bortezomib-refractory multiple myeloma (MM) patients is very poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months. Therefore new treatment modalities are urgently needed. In this respect, several new drugs have recently been approved for the treatment of double refractory MM (such as pomalidomide, carfilzomib, and daratumumab). However, next to the development of new drugs, also the strategy of combining drugs with synergistic activity may result in significant clinical benefit for patients with advanced myeloma.Lenalidomide has well-described immunomodulatory effects, even in the setting of lenalidomide-refractory disease. Similarly, administration of continuous low-dose cyclophosphamide (metronomically dosed) has direct anti-tumor activity, as well as several well-characterized immunomodulatory effects. We have previously shown in a retrospective study that lenalidomide combined with continuous low-dose oral cyclophosphamide (endoxan) and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients.
Aims
To further evaluate this combination, we initiated a prospective phase I/II study to determine the optimal dosing schedule of lenalidomide, low-dose oral cyclophosphamide and prednisone, and to assess its efficacy and safety in lenalidomide-refractory MM patients.
Methods
82 lenalidomide-refractory MM patients were included in this trial; 21 were included in the phase 1 dose-finding part with a classic 3+3 dose-escalation design (5 dose-levels) and 61 patients were included in the phase II part of this trial in which all patients were treated at the maximum tolerated dose (MTD).
Results
The median age of the 82 patients in this phase I/II trial was 66 years (range 41-82); 71% were male. The median duration from diagnosis was 48 months (range 5-169), median number of prior therapies was 3 (range 1-6), and 50 patients (61%) had previously received autologous SCT. All patients were lenalidomide-refractory, 71 (87%) had prior bortezomib treatment, and 54 (66%) had both lenalidomide- and bortezomib-refractory MM. 41% of the patients had high-risk cytogenetic abnormalities as determined by FISH.The MTD was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous oral cyclophosphamide (50 mg/day) and prednisone (20 mg/day). Sixty-seven patients were treated at the MTD (6 in dose-level 4 of phase I and 61 in phase II part of the study). Forty-four of these patients (67%) achieved a partial response or better, including 12 patients (18.2%) with a very good partial response and 3 (4.5%) with a complete remission. Eleven patients (16%) achieved a minimal response, translating to an overall 83% clinical benefit rate. After a median follow-up of 24.5 months median PFS and OS were 12.1 and 29.0 months respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities. At the MTD, neutropenia (22%) and thrombocytopenia (22%) were the most common grade ≥3 hematological adverse events. Infections (21%) were the most common grade ≥3 non-hematological adverse events.
Conclusion
REP is a well-tolerated regimen and induces a high response rate with prolonged PFS and OS in lenalidomide-refractory MM patients. REP should be considered a valuable salvage option for lenalidomide-refractory MM patients.This trial was registered at www.clinicaltrials.gov as #NCT01352338.
Session topic: E-poster
Keyword(s): Multiple myeloma, Refractory
Type: Eposter Presentation
Background
The outcome of lenalidomide- and bortezomib-refractory multiple myeloma (MM) patients is very poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months. Therefore new treatment modalities are urgently needed. In this respect, several new drugs have recently been approved for the treatment of double refractory MM (such as pomalidomide, carfilzomib, and daratumumab). However, next to the development of new drugs, also the strategy of combining drugs with synergistic activity may result in significant clinical benefit for patients with advanced myeloma.Lenalidomide has well-described immunomodulatory effects, even in the setting of lenalidomide-refractory disease. Similarly, administration of continuous low-dose cyclophosphamide (metronomically dosed) has direct anti-tumor activity, as well as several well-characterized immunomodulatory effects. We have previously shown in a retrospective study that lenalidomide combined with continuous low-dose oral cyclophosphamide (endoxan) and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients.
Aims
To further evaluate this combination, we initiated a prospective phase I/II study to determine the optimal dosing schedule of lenalidomide, low-dose oral cyclophosphamide and prednisone, and to assess its efficacy and safety in lenalidomide-refractory MM patients.
Methods
82 lenalidomide-refractory MM patients were included in this trial; 21 were included in the phase 1 dose-finding part with a classic 3+3 dose-escalation design (5 dose-levels) and 61 patients were included in the phase II part of this trial in which all patients were treated at the maximum tolerated dose (MTD).
Results
The median age of the 82 patients in this phase I/II trial was 66 years (range 41-82); 71% were male. The median duration from diagnosis was 48 months (range 5-169), median number of prior therapies was 3 (range 1-6), and 50 patients (61%) had previously received autologous SCT. All patients were lenalidomide-refractory, 71 (87%) had prior bortezomib treatment, and 54 (66%) had both lenalidomide- and bortezomib-refractory MM. 41% of the patients had high-risk cytogenetic abnormalities as determined by FISH.The MTD was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous oral cyclophosphamide (50 mg/day) and prednisone (20 mg/day). Sixty-seven patients were treated at the MTD (6 in dose-level 4 of phase I and 61 in phase II part of the study). Forty-four of these patients (67%) achieved a partial response or better, including 12 patients (18.2%) with a very good partial response and 3 (4.5%) with a complete remission. Eleven patients (16%) achieved a minimal response, translating to an overall 83% clinical benefit rate. After a median follow-up of 24.5 months median PFS and OS were 12.1 and 29.0 months respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities. At the MTD, neutropenia (22%) and thrombocytopenia (22%) were the most common grade ≥3 hematological adverse events. Infections (21%) were the most common grade ≥3 non-hematological adverse events.
Conclusion
REP is a well-tolerated regimen and induces a high response rate with prolonged PFS and OS in lenalidomide-refractory MM patients. REP should be considered a valuable salvage option for lenalidomide-refractory MM patients.This trial was registered at www.clinicaltrials.gov as #NCT01352338.
Session topic: E-poster
Keyword(s): Multiple myeloma, Refractory
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