IMPACT OF RENAL IMPAIRMENT ON THE EFFICACY AND SAFETY OF MELPHALAN-PREDNISONE-LENALIDOMIDE (LEN) INDUCTION FOLLOWED BY LEN MAINTENANCE IN NEWLY DIAGNOSED MULTIPLE MYELOMA: MM-015 POST-HOC ANALYSIS

Background:

MM-015 is a phase 3 pivotal trial in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), which found that induction with melphalan-prednisone-LEN followed by LEN maintenance (MPR-R) significantly prolonged progression-free survival (PFS; 31 mos) compared with MPR (14 mos) or MP (13 mos) (P < 0.001 for both comparisons).

Aims:

n this analysis, we retrospectively compare the efficacy and safety of MPR-R, MPR, and MP in the subset of MM-015 patients with moderate renal impairment (RI; defined as creatinine clearance [CrCl] < 60 mL/min).

Methods:

Treatment regimens have been presented previously (Palumbo A, et al. N Engl J Med. 2012;366:1759-69). NDMM patients were randomized to MPR-R (MPR induction followed by LEN maintenance [10 mg, D1–21/28-day cycle] until disease progression or unacceptable adverse events [AEs], or MPR or MP without maintenance therapy. CrCl was estimated using the Cockcroft-Gault formula and, for this analysis, patients were divided into two groups: CrCl < 60 mL/min and CrCl ≥ 60 mL/min. Patients with severe RI (serum creatinine > 2.5 mg/dL [> 221 μmol/L]) were excluded from the trial. Dose adjustments were not recommended for patients with RI.

Results:

CrCl < 60 mL/min was observed in 51% of MPR-R patients, 45% of MPR patients, and 49% of MP patients. Among patients with CrCl < 60 mL/min, median PFS was significantly higher with MPR-R (26 mos [95% confidence interval (CI): 14–48]) than MPR (13 mos [95% CI: 12–15]) or MP (14 mos [95% CI: 12–16]; P < 0.001 for both). CrCl < 60 mL/min was not a significant prognostic factor for PFS in a Cox proportional model (P = 0.69). The most common grade 4 AEs were hematologic, occurring predominantly during induction (Table). The proportion of patients with moderate RI who died during the study was similar across treatment groups: 10% (MPR-R), 7% (MPR), and 8% (MP) (Table); ≤ 1% of deaths in the RI population were associated with RI or disease progression. Updated data will be presented at the meeting.

Summary / Conclusion:

In patients with moderate RI, PFS was significantly improved with continuous LEN treatment with MPR-R compared with MPR or MP, and with an acceptable safety profile, which is consistent with the overall trial results. However, CrCl and AEs should be closely monitored in this patient population.

Keywords: Immunomodulatory thalidomide analog, Maintenance, Multiple myeloma, Renal impairment

Abstrakta v časopise Haematologica 2013, Suppl1

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