Lenalidomide in Combination With Dexamethasone in Elderly Patients With Advanced, Relapsed or Refractory Multiple Myeloma and Renal Failure

Abstract

Salvage therapy of elderly patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this can potentially limit the therapeutic options. Both thalidomide and bortezomib have proven effective in these patients, with an acceptable toxicity, while, in clinical practice, lenalidomide is generally not considered a first-choice drug for MM patients with renal failure as early reports showed an increased hematological toxicity unless appropriate dose reduction is applied. Aim of this study was a retrospective evaluation of the efficacy of the combination Lenalidomide + Dexamethasone in a population of elderly MM patients treated in 5 Italian Centers. The study included 20 consecutive MM patients (9 M, 11 F, median age 76.5 years) with relapsed (N= 6) or refractory (N=13) MM and moderate to severe renal failure, defined as creatinine clearance (Cr Cl) < 50ml/min. Four patients were undergoing hemodyalisis at study entry. 85 % of the patients had been previously treated with bortezomib-containing regimens. Lenalidomide dose was adjusted according to renal function and patients clinical conditions Median treatment duration was 16 months (1–22), therapy was interrupted after 1 21-day cycle in 2 patients. Grade III–IV neutropenia was observed in 7 patients (35%); grade III–IV non hematological toxicity was recorded in 3 cases (28%). A > partial response was observed in 8 patients (40%), 1 of whom obtained a VGPR; 4 additional patients achieved a minor response. Median response duration was 16 months (range 2–19+ months). A complete and partial renal response was obtained in 4 and 3 patients, respectively, all of them were responsive to Lenalidomide-dexamethasone According to our data, LEN+DEX has shown efficacy and acceptable toxicity in this population of elderly patients with advanced MM and renal failure

Dose-adjusted Lenalidomide Combined with Low-dose Dexamethasone Rescues Older Patients with Bortezomib-resistant Multiple Myeloma

“…Our cohort consisted of consecutive, unselected patients treated at a single center, all of whom received similar supportive care. Consequently, we found that dose-adjusted Len plus low-dose Dex improved the renal function in the older RRMM patients with RI, as previously described (16).…”

“…Several other studies have tested the efficacy of Len combined with Dex in RRMM patients with RI, including Len adjusted for the renal function (6,9,18,19). With the exception of one study (16), however, all of the patients received a dose of >80 mg of Dex per cycle, which may increase the risk of severe infections in older RRMM patients with RI.…”

Current Trends of Renal Impairment in Multiple Myeloma

“…This study showed that with careful monitoring and with appropriate dose adjustments, lenalidomide could be used for relapsing or refractory MM in patients requiring dialysis. Overall, the results of studies to date indicate that lenalidomide therapy is an important treatment option in the management of MM in patients with RI [101,102,103,104,105]. …”

Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study

“…Several studies have assessed the role of treatment combinations based on bortezomib, thalidomide, and lenalidomide in newly diagnosed young and elderly patients as well as in those with relapsed/refractory disease [25][26][27][28][29][30][31] with different degrees of renal impairment.…”