Contributions
Abstract: PB2164
Type: Publication Only
Background
Elderly patients with multiple myeloma (MM) frequently are ineligible for intensive therapies including autologous stem cell transplantation and require an individualized therapy.
Aims
This study investigated efficacy and safety of the 3-drug-combination bendamustine/prednisone/bortezomib (BPV regimen) as first-line therapy for elderly patients with multiple myeloma (MM).
Methods
Elderly patients with symptomatic MM not eligible for intensive therapy and autologous stem cell transplantation were enrolled in this phase IIb study for first-line treatment with the bendamustine/prednisone/bortezomib regimen. All 46 patients were included in the safety and intention-to-treat (ITT) analysis for the secondary objectives. 34 patients were eligible for the primary efficacy analysis of overall response rate (ORR) defined as CR and PR in the per protocol (PP) population, which consisted of all patients who completed at least 3 cycles of BPV therapy and were evaluable for response. For evidence of superiority compared to historical MPV (melphalan, prednisone, bortezomib) data we postulated the lower confidence boundary for the primary endpoint of ORR to be at least 67%. The study was conducted as a multicenter, single-arm, open-label clinical trial. The treatment regimen consisted of bendamustine 90 mg/m2 iv: d1, 2; prednisone 60 mg/m2 po: d1-4; bortezomib 1.3 mg/m2 iv: cycle 1 [d1-d42]): d1, 4, 8, 11, 22, 25, 29, 32; cycle 2-9 [d1-28]: d1, 8, 11, 22. Treatment was scheduled for 9 cycles with 42 d for cycle 1 and 28 d for cycle 2-9.
Results
From November 2014 to October 2016, 46 patients were included into the trial. Patients had the following key baseline characteristics: median age 76 years, female: 61%, median glomerulofiltration rate (GFR) of 64 ml/min.
The ORR was 76.5% with a lower 95% confidence bound of 62.7%. The clinical benefit rate (CBR) including MR was 91.2%.
19 patients with renal impairment at baseline had a median GFR of 42.6 ml/min [range 12.9-49.7]. A renal response (defined as improvement of renal function by IMWG criteria, Dimopoulos et al J Clin Oncol 2010) was observed in 11 pts.. 6 pts. achieved a complete recovery of the renal function.
The BPV regimen was well tolerated. 33 of 46 pts. (71.7%) experienced AEs of CTC grade 3 and 4. The most common grade 3/4 AEs were neutropenia (26%), infections (26%), and thrombocytopenia (19.5%). Pneumonia was documented in 4 patients. Cardiac grade 3 and 4 complications were atrial fibrillation (3 events) and hypertension (2 events). No new safety signals for the study drugs were observed. 46 % of patients developed at least 1 SAE.
Conclusion
BPV may serve as a well tolerated first-line regimen for transplant ineligible elderly MM patients with an encouraging ORR of 76%. BPV can be also considered, if a fast renal response is required in patients with myeloma induced renal impairment. However, the study did not provide statistical evidence of superiority compared to historical MPV response data.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): bendamustine, Elderly, Multiple Myeloma, Velcade
Abstract: PB2164
Type: Publication Only
Background
Elderly patients with multiple myeloma (MM) frequently are ineligible for intensive therapies including autologous stem cell transplantation and require an individualized therapy.
Aims
This study investigated efficacy and safety of the 3-drug-combination bendamustine/prednisone/bortezomib (BPV regimen) as first-line therapy for elderly patients with multiple myeloma (MM).
Methods
Elderly patients with symptomatic MM not eligible for intensive therapy and autologous stem cell transplantation were enrolled in this phase IIb study for first-line treatment with the bendamustine/prednisone/bortezomib regimen. All 46 patients were included in the safety and intention-to-treat (ITT) analysis for the secondary objectives. 34 patients were eligible for the primary efficacy analysis of overall response rate (ORR) defined as CR and PR in the per protocol (PP) population, which consisted of all patients who completed at least 3 cycles of BPV therapy and were evaluable for response. For evidence of superiority compared to historical MPV (melphalan, prednisone, bortezomib) data we postulated the lower confidence boundary for the primary endpoint of ORR to be at least 67%. The study was conducted as a multicenter, single-arm, open-label clinical trial. The treatment regimen consisted of bendamustine 90 mg/m2 iv: d1, 2; prednisone 60 mg/m2 po: d1-4; bortezomib 1.3 mg/m2 iv: cycle 1 [d1-d42]): d1, 4, 8, 11, 22, 25, 29, 32; cycle 2-9 [d1-28]: d1, 8, 11, 22. Treatment was scheduled for 9 cycles with 42 d for cycle 1 and 28 d for cycle 2-9.
Results
From November 2014 to October 2016, 46 patients were included into the trial. Patients had the following key baseline characteristics: median age 76 years, female: 61%, median glomerulofiltration rate (GFR) of 64 ml/min.
The ORR was 76.5% with a lower 95% confidence bound of 62.7%. The clinical benefit rate (CBR) including MR was 91.2%.
19 patients with renal impairment at baseline had a median GFR of 42.6 ml/min [range 12.9-49.7]. A renal response (defined as improvement of renal function by IMWG criteria, Dimopoulos et al J Clin Oncol 2010) was observed in 11 pts.. 6 pts. achieved a complete recovery of the renal function.
The BPV regimen was well tolerated. 33 of 46 pts. (71.7%) experienced AEs of CTC grade 3 and 4. The most common grade 3/4 AEs were neutropenia (26%), infections (26%), and thrombocytopenia (19.5%). Pneumonia was documented in 4 patients. Cardiac grade 3 and 4 complications were atrial fibrillation (3 events) and hypertension (2 events). No new safety signals for the study drugs were observed. 46 % of patients developed at least 1 SAE.
Conclusion
BPV may serve as a well tolerated first-line regimen for transplant ineligible elderly MM patients with an encouraging ORR of 76%. BPV can be also considered, if a fast renal response is required in patients with myeloma induced renal impairment. However, the study did not provide statistical evidence of superiority compared to historical MPV response data.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): bendamustine, Elderly, Multiple Myeloma, Velcade