Experience with Long-Term Lenalidomide (LEN) Treatment in the Clinical Setting: Results From the UK Revlimid^® Treatment Continuation Scheme™ (TCS)

Existing evidence has shown that continuing treatment with LEN plus dexamethasone (LEN-DEX) until disease progression in responding patients (pts) with relapsed/refractory multiple myeloma (RRMM) is associated with improved survival. In accordance with National Institute of Clinical Excellence (NICE) guidelines, LEN-DEX is reimbursed for treatment of RRMM pts after ≥2 therapies in England and Wales (current license after ≥1 prior therapy). The TCS database was designed as part of the NICE agreed pt access scheme, to track the duration of treatment for RRMM pts prescribed LEN-DEX. This scheme was not designed to record reasons for dose adjustments or treatment discontinuation. We studied LEN starting dose, dose modifications, and duration of treatment (in an anonymized dataset generated for statistical analysis).

This prospective cohort analysis focused on pts enrolled in the TCS program between 1 July 2009 and 1 May 2010, to allow pts to be followed up for at least 2 years, unless they discontinued treatment earlier. The cut-off date was 30 June 2012. Associations between ordered categorical variables were measured by Spearman's rank correlation or Pearson's correlation for continuous variables. Baseline covariates (age and starting dose) were modeled using multivariable logistic regression with possible interactions considered. Statistical significance was considered at the 5% significance level.

A total of 1,286 pts with RRMM from 185 UK treatment centers were evaluable. The median age was 69 yrs (range, 34–91); 427 pts were aged <65 yrs (33%), 529 pts were aged 65–74 yrs (41%), and 330 pts were aged >75 yrs (26%).

Majority of pts (n = 835; 65%) initiated LEN treatment according to the recommended starting dose of 25 mg/d; 180 (14%) pts started at 15 mg, 212 (16%) at 10 mg, and 59 (5%) at 5 mg. Dose modifications were reported in 50% of pts, and the median number of changes in dose per subject was 1 (range, 0–15). The greatest percentage of dose modifications per cycle occurred in pts with the lowest starting dose (5 mg). A total of 340 (45%) pts who started on 25 mg/d and received >1 cycle required no dose adjustments. There was a relationship between dose adjustment and duration of treatment; pts without an adjustment received an average of 9.1 cycles while those with at least one form of adjustment received 14.3 cycles (P < 0.001).

The median number of cycles administered was 7 (range, 1–38), similar to that seen in LEN clinical trials (median 9.2 mos in pts with ≥2 prior therapies); 456 (35%) pts remained on therapy for ≥12 cycles and 201 (16%) pts remained on therapy for ≥24 cycles. Six percent of all pts receiving ≥24 cycles had dose modifications directly after cycle 1, with the percentage of dose modifications steadily decreasing from cycle 6 onwards. There was a positive association between a higher starting dose and longer treatment duration (P < 0.001). Of the pts who started on 25 mg/d and ≤10 mg/d, 18% and 9% received ≥24 cycles, respectively.

There was a significant negative correlation between age and the number of cycles administered (P = 0.018): of the pts aged <75 yrs, 17% received ≥24 cycles; pts ≥75 yrs, 11% received ≥24 cycles.

Multivariate analyses were carried out to evaluate predictors for treatment duration. Age and starting dose were both found to be statistically significant predictors for a treatment duration lasting ≥24 mos: pts aged <65 yrs and 65–74 yrs were 1.61 times (P = 0.030) and 1.65 times (P = 0.019) more likely to have a duration >24 mos compared with pts ≥75 years, respectively. Pts were 2 times (P = 0.010) more likely to achieve ≥24 cycles if receiving 25 mg as their starting compared with those starting on 10 mg/d.

Results of this “real-world” clinical analysis support 25 mg LEN as an optimal starting dose for the majority of RRMM pts. A positive correlation between the recommended starting dose and longer treatment duration was observed. In addition, individual dose adjustments of LEN during therapy appeared to be associated with extended treatment duration in this setting.

Williams:Celgene, Janssen-Cilag: Honoraria. Simcock:Celgene: Employment. Lodhi:Celgene: Employment. Robinson:Celgene: Employment. Davies:Celgene, Johnson & Johnson, Onyx, Novartis: Honoraria, Speakers Bureau; Merck: Speakers Bureau.