Post-Approval Safety Study (PASS) of Lenalidomide Compared with Other Treatments In Patients with Relapsed or Refractory Multiple Myeloma: Evaluation of Peripheral Neuropathy In the First 1,011 Patients

Lenalidomide plus dexamethasone was EMEA approved in 2007 for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Subsequently, an observational patient cohort study was implemented to characterize the safety profile of lenalidomide in clinical practice, and to place the incidence of adverse events (AEs) into context with those occurring in patients with MM receiving other treatments second line or later. A secondary objective of the study was to assess the evolution or resolution of peripheral neuropathy (PN) in patients taking lenalidomide, who had pre-existing PN at baseline.

Data were collected prospectively from 1,011 patients with MM, in 177 institutions in 15 European countries. Patients had received at least one prior therapy and were commencing a new treatment with prescribed medication in accordance with normal clinical practice at the time of enrollment. No additional treatments or investigations outside of normal clinical practice were required. PN status was assessed by physicians according to their normal clinical practice. PN was recorded at baseline and, if present, the status was subsequently recorded at all following data collection points until the patient discontinued study treatment. For those patients who did not have PN at baseline, any new occurrence of PN was documented as an AE. Data cutoff for this analysis was May 4, 2010.

Of the 1,011 patients who entered the study, 658 patients started lenalidomide-, 207 bortezomib-, and 53 thalidomide-based therapies; 43 patients commenced other therapies and 50 had missing data. Median Kaplan-Meier estimated treatment duration was 6.4 months for lenalidomide, 3.8 for bortezomib, and 4.8 for thalidomide. Baseline PN was reported in 39% (254/658) of patients in the lenalidomide cohort: 22% (144/658) were reported to be due to previous bortezomib and 18% (118/658) were due to previous thalidomide. In the bortezomib cohort 21% (43/207) had baseline peripheral neuropathy: 3% (6/207) were reported due to previous bortezomib and 13% (27/207) due to previous thalidomide. Baseline PN due to prior vincristine use was low (2% of patients), and non-drug induced PN was between 4–6% in the three cohorts overall. Observed PN in the lenalidomide cohort was 42% (89/213) at baseline and 29% (62/213) at 4 months, compared with 26% at baseline (16/61) and 23% (14/61) at 4 months in the bortezomib cohort. There was no change over the 4 month period in the thalidomide cohort (16% _3/19). Treatment discontinuations due to AEs were highest in the thalidomide cohort (24.5%), and similar in the lenalidomide (14.1%) and bortezomib (15.5%) cohorts. However, patient discontinuations due to PN were six times higher in the bortezomib (4.8%) cohort compared with the lenalidomide cohort (0.8%). The incidence of drug-related PN and grade 3* or 4** drug-related PN was four times lower in the lenalidomide cohort compared with the bortezomib cohort.

In this unselected group of patients taken from normal clinical practice and treated with lenalidomide-, bortezomib-, or thalidomide-based therapies, lenalidomide demonstrated a low incidence of drug-related PN. A high proportion of patients commencing treatment with lenalidomide had baseline PN due to their previous anti-myeloma therapy. Preliminary data on these patients at 4 months of treatment indicated a trend towards improvement of PN in patients receiving lenalidomide. Discontinuations due to PN were low in the lenalidomide cohort compared with the bortezomib cohort.

Delforge:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Ortho-Biotech: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Hajek:Celgene Corporation: Honoraria; Janssen-Cilag: Honoraria; Merck, Sharp, and Dohme: Honoraria. Lokhorst:Celgene Corporation: Speakers Bureau. Collins:Celgene Corporation: Employment. Rosettani:Celgene Corporation: Employment. Brandenburg:Celgene Corporation: Employment.