Safety and tolerability of pomalidomide-based regimens (pomalidomide-carfilzomib-dexamethasone with or without cyclophosphamide) in relapsed/refractory multiple myeloma and severe renal dysfunction: a case series

Abstract Introduction Serious renal failure represents a main complication of Multiple Myeloma (MM). An estimated 25% to 50% of patients are affected during the course of their disease. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in more than 25%. The window of opportunity for reversal of renal impairment is rather small making an immediate and highly active treatment strategy mandatory. Bortezomib and bendamustine have turned out to be quickly acting and effective drugs in the treatment of MM. Methods Between March 2005 and March 2013, 36 patients (median age 64; range 32-81 years) with relapsed/refractory MM and light chain induced renal failure (creatinine clearance <60ml/min) were treated with bendamustine 60mg/qm on day 1 and 2, bortezomib 1.3mg/qm on day 1, 4, 8 and 11, and prednisone 100mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days. Patients were divided into two groups: group A (n=20) consisted of patients with moderate or severe renal dysfunction (eGFR 15-59ml/min) and group B (n=16) of patients with renal failure/dialysis (eGFR <15ml/min). Results The median number of the BPV-treatment was 2 (1-7) cycles. 24 patients (67%) responded after at least one cycle of chemotherapy with 3 CR, 3 nCR, 6 VGPR, and 12 PR. Six patients had MR, 2 patients stable disease and 4 patients had a progress. With a median follow up of 22 months of the surviving patients, median PFS and OS for patients with moderate or severe renal dysfunction (group A) were 10 months and 25 months, respectively. Outcome for these patients was significantly better compared to patients with renal failure/dialysis (group B) with a median PFS and OS of 3 months and 7 months, respectively (p<0.02). Eleven patients showed a CRrenal, 5 patients a PRrenal and 15 patients a MRrenal. Median time to first renal response and best renal response were 21 days and 42 days, respectively. The most common severe side effect was grade 3-4 thrombocytopenia in 81% of the patients. Grade 3-4 neutropenia was observed in 50% of the patients. Moderate to severe infections were seen in 13 patients. Summary These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in patients with relapsed/refractory MM and light chain induced renal failure. Disclosures: No relevant conflicts of interest to declare.

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Utility of bortezomib retreatment among patients with refractory multiple myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17549 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17549-17549

Author(s):

J. L. Wolf ◽

A. L. Leblanc MT ◽

D. S. Battleman ◽

B. Davis ◽

J. R. Lyandres ◽

...

Keyword(s):

Multiple Myeloma ◽

Initial Treatment ◽

Plasma Cells ◽

Small Sample Size ◽

Case Series ◽

Small Sample ◽

Statistical Testing ◽

M Protein ◽

Retrospective Case ◽

Refractory Multiple Myeloma

17549 Background: Bortezomib (VELCADE; Vc) has emerged as the standard of care for patients with relapsed or refractory multiple myeloma (MM). However, following initial Vc therapy, its utility in recurrent disease is unclear. This retrospective case series provides preliminary evidence of the safety and efficacy of Vc in the retreatment of patients with recurrent MM. Methods: An observational case series was developed based on a medical records review of all patients (N = 10) who completed Vc retreatment following completion of initial Vc therapy. Best response was measured as the greatest mean % reduction in the treatment response measure: serum/urine M-protein or plasma cells. Differences between initial treatment and retreatment efficacy and Vc-related hospitalizations were assessed using descriptive statistics. Results: During initial treatment 44% of patients responded to Vc (≥50% M-protein (3/9) or plasme cell reduction (1/9, 1 pt NA). At retreatment 50% of patients responded (5/10). Following initial Vc therapy, the median treatment-free interval was just over 13 months (56.6 weeks). One patient experienced a dose reduction due to peripheral neuropathy (grade 2) during retreatment, compared to two patients with neuropathy (grade 3) during initial treatment. Termination of therapy due to any unmanageable toxicity was much lower during retreatment (14.3% vs 62.5%). Finally, none of the patients were hospitalized for Vc-related events during retreatment, compared with two patients during initial treatment. Conclusions: Vc retreatment appears to be as effective as initial treatment in terms of response, and may actually yield less toxicity and hospitalizations. Even though this small sample size precluded statistical testing, the observed patterns are instructive and additional prospective trials are currently ongoing. However, based on these preliminary data, prolonged disease control may be achieved with repeated use. [Table: see text]

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