Prognostic impact of rapid reduction of involved free light chains in multiple myeloma patients under first-line treatment with Bendamustine, Prednisone, and Bortezomib (BPV).

INTRODUCTION: Light chain involvement is observed in almost every patient (pt) with newly diagnosed multiple myeloma (MM). Owing to a relatively short half-life, rapid reduction in the involved free light chain (iFLC) is of potential prognostic value. METHODS: This retrospective analysis included 92 pts with newly diagnosed MM treated with bendamustine, prednisone, and bortezomib (BPV). RESULTS: After a median number of two (range 1-5) BPV cycles, the majority of pts (n = 86; 93%) responded with either sCR (n = 21), CR (n = 1), nCR (n = 25), VGPR (n = 20), or PR (n = 19). PFS and OS at 48 months were 39% and 67%, respectively. At baseline, 79 out of 92 pts (86%) had iFLC levels above the upper standard level and an abnormal ratio of involved to uninvolved free light chain ≥ 8. In a subgroup analysis of these pts, we evaluated the prognostic importance of an early reduction of the iFLC during the first two BPV cycles. A reduction ≥ 50% of the iFLC on day 8 of the first cycle was observed in 31 of 69 pts. These pts had a significantly better median PFS of 49 months as compared to 20 months in 38 pts with a lower iFLC reduction (p = 0.002). In contrast, OS did not differ significantly with a 48 months survival of 77% vs 69% (p > 0.05). CONCLUSION: These results indicate that a rapid decrease in the iFLC on day 8 is an early prognostic marker for newly diagnosed MM pts undergoing BPV treatment.

Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077).

INTRODUCTION: While lenalidomide monotherapy is established for relapsed and/or refractory multiple myeloma (MM) treatment, combination therapies including lenalidomide are still under investigation in a number of phase 2/3 studies. In the current study, a treatment regime of lenalidomide (Revlimid®), bendamustine and prednisolone (RBP) was tested in patients with relapsed/refractory MM. METHODS: In the previously completed phase 1 study RBP with a dose of 75 mg/m2 bendamustine days 1-2, prednisolone 100 mg days 1-4 and 25 mg lenalidomide days 1-21 was well tolerated. RESULTS: Between July 2011 and September 2013, 25 patients were included in this analysis. The median number of previous treatments was 1 (range 1-2). Twenty-two patients (88%) responded after at least two cycles of RBP (one sCR, five nCR, eight VGPR and eight PR). The median time to first haematological response was 28 days, and median time to best response was 56 days. Due to increased haematological toxicity a dose reduction in most patients required in subsequent cycles of therapy. The median progression-free and overall survival was 22 and 38 months, respectively. In conclusion RBP is a highly effective therapy for patients with relapsed/refractory MM. In contrast to our phase 1 study, dose reduction was necessary in many patients because of haematological toxicity.

Successful treatment of patients with newly diagnosed/untreated light chain multiple myeloma with a combination of bendamustine, prednisone and bortezomib (BPV).

INTRODUCTION: Patients with light chain myeloma frequently have a light chain tubular cast nephropathy, which can lead to severe renal impairment. In the present retrospective study, bortezomib was combined with other active substances like bendamustine and prednisone (BPV), in order to assess the efficacy and toxicity of the combination therapy in patients with light chain multiple myeloma. METHODS: Between September 2008 and May 2015, 25 patients with newly diagnosed light chain multiple myeloma were treated with bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 once every 21 days (BPV). Prior to treatment, 4 patients (16%) had moderate renal dysfunction and 14 patients (56%) severe renal dysfunction or renal failure/dialysis. RESULTS: The median number of the BPV cycles was 2 (1-5). 24 patients (96%) responded with 4 stringent complete responses, 6 near-complete responses, 5 very good partial responses and 9 partial responses. The myeloma light chains decreased rapidly, reaching the best response after the first cycle in 9 and after the second cycle in additional 12 patients. 17 patients discontinued therapy after median 2 cycles of BPV treatment to receive autologous or allogeneic SCT. All together 12 of 18 patients with at least moderate renal failure improved their renal function. 3 of the 6 dialysis-dependent patients became dialysis-independent. With a median follow-up of 27 months, median progression-free survival and overall survival for patients at 30 months were 68 and 96%, respectively. The most common severe side effect was grade 3/4 leukocytopenia in 20% of the patients. Grade 3/4 thrombocytopenia was observed in 12% of the patients. Moderate to severe infection were seen in six patients. We conclude that BPV is effective and well tolerated in patients with newly diagnosed/untreated light chain multiple myeloma.

Stem cell mobilization and autologous stem cell transplantation after pretreatment with bendamustine, prednisone and bortezomib (BPV) in newly diagnosed multiple myeloma.

INTRODUCTION: Reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. MATERIALS AND METHODS: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with MM who had received at least one cycle of a BPV-induction therapy consisting of bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m(2) and G-CSF (2 × 5 µg/kg). Apheresis was started as soon as peripheral CD34(+) counts exceeded 20 × 10(6)/L with a harvest target of 8 × 10(6) CD34(+)/kg. The minimal accepted target was 2 × 10(6) CD34(+)/kg. The transplantation conditioning therapy consisted of melphalan 200 mg/m(2). RESULTS: A median number of two (range 1-5) BPV cycles were given. The majority of patients (n = 31, 89 %) responded with two sCR, five nCR, 11 VGPR and 13 PR after BPV induction. Three patients had MR, and one SD. Stem cell mobilization and harvest were successful in all patients. In 19 of 35 patients (54 %), a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4), and the median CD34(+) cell-count/kg was 13.5 (range 3.2-33.1)  × 106. All patients received an autologous SCT. Engraftment was successful in 34 of 35 patients. The median time to a leukocyte count >l × 10(9)/L was 11 days, and the time to untransfused platelet count of >50 × 10(9)/L was 13 days. Thirty-four patients (97 %) responded after the autologous SCT with 11 sCR, two CR, seven nCR, seven VGPR and seven PR. The progression-free survival at 18 months was 87 %, and overall survival was 92 %. CONCLUSION: Stem cell mobilization and autologous SCT are feasible in MM patients who have received BPV-induction therapy .

Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma.

INTRODUCTION: Bortezomib is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination in patients with multiple myeloma (MM). In the present protocol, bortezomib was combined with bendamustine and prednisone, in order to assess the efficacy and safety of this combination therapy in patients with newly diagnosed/untreated MM. METHODS: Between June 2006 and October 2013, 49 patients with newly diagnosed/untreated MM were treated with bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 bendamustine, prednisone and bortezomib (BPV) once every 21 days. Patients were divided into three groups: group A (n = 19) consisted of patients with normal renal function or mild dysfunction (eGFR ≥ 60 ml/min), group B (n = 15) patients with moderate or severe renal dysfunction (eGFR 15-59 ml/min) and group C (n = 15) patients with renal failure/dialysis (eGFR <15 ml/min). RESULTS: A median number of two (range 1-5) BPV treatment cycles were given to the patients. The majority of the patients (n = 40, 82 %) responded after at least one cycle of BPV therapy with five stringent complete responses (CRs), nine near complete responses, 12 very good partial responses and 14 partial responses. Five patients had MR, three stable and one progressive disease. After a median observation time of 13 months, progression-free survival (PFS) and overall survival (OS) at 12 months were 92 and 94 %, respectively, for patients with normal renal function or mild renal dysfunction (group A) and 83 and 93 %, respectively, for patients with moderate or severe renal dysfunction (group B). Outcome for these patients was slightly better but not statistically significantly better than that for patients with renal failure/dialysis (group C), who had a PFS, and OS of 66 % (p = 0.08) and 73 % (p = 0.05), respectively. These results indicate that this BPV combination is feasible, effective and well tolerated in patients with newly diagnosed MM and normal or impaired renal function.

Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with relapsed or refractory multiple myeloma and light chain-induced renal failure.

INTRODUCTION: Serious renal failure represents a severe complication of multiple myeloma (MM), with an estimated 25-50 % of patients being affected. Both bortezomib and bendamustine have been identified as quickly acting, effective and well-tolerated drugs and might therefore constitute an adequate combination regimen for patients presenting with light chain-induced renal failure. METHODS: Between March 2005 and March 2013, 36 patients with relapsed/refractory MM and light chain-induced renal failure (creatinine clearance <60 ml/min) were treated with bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 (BPV). Patients were divided according to severity of renal impairment into group A (n = 20) with moderate or severe renal dysfunction (eGFR 15-59 ml/min) and group B (n = 16) with renal failure/dialysis (eGFR <15 ml/min). RESULTS: Twenty-four patients (67 %) responded with three CR, three nCR, six VGPR and 12 PR. Six patients had minor response, two stable and four progressive disease. With a median follow-up period of 22 months, median progression-free survival (PFS) and overall survival (OS) for patients of group A were 10 and 25 months, respectively. This outcome was significantly better compared to patients of group B with a median PFS and OS of 3 and 7 months, respectively. Eleven patients showed a CRrenal, five a PRrenal and 15 a MRrenal. These results indicate that this BPV combination is feasible, effective and well tolerated in patients with relapsed/refractory MM and light chain-induced renal failure.

Successful treatment of patients with newly diagnosed/untreated multiple myeloma and advanced renal failure using bortezomib in combination with bendamustine and prednisone.

PURPOSE: Renal failure is a frequent complication of multiple myeloma (MM) and, if present at diagnosis, a considerable risk factor for outcome. Treatment with chemotherapy and/or new agents may result in recovery of renal function in up to 50 % of patients. The window of opportunity to reverse renal impairment is, however, rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as bendamustine has been demonstrated to be potent drugs in the treatment of MM. METHODS: A total of 18 patients with newly diagnosed/untreated MM and renal insufficiency (GFR < 35 ml/min) were treated with bendamustine, prednisone, and bortezomib (BPV). RESULTS: The majority of them (n = 15; 83 %) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow-up of 17 months, PFS at 18 months was 57 % and OS was 61 %. The myeloma protein decreased rapidly, reaching the best response after the first cycle in four and after the second cycle in additional seven patients. Thirteen patients (72 %) improved their renal function after treatment. CONCLUSION: We conclude that the combination of bortezomib, bendamustine, and prednisone is effective and well tolerated in patients with a newly diagnosed MM and renal failure.