Clin Cancer Res 2020 Aug 17
Efficacy and Tolerability of High- versus Low-dose Lenalidomide Maintenance Therapy of Multiple Myeloma after Autologous Blood Stem Cell Transplantation.
Abstract
Purpose
For multiple myeloma, high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10-15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated.
Patients and methods
In a multicenter, randomized, open-label trial, patients with multiple myeloma after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS).
Results
Ninety-four patients (median age, 58 years) were randomized to either arm, with 22% having International Staging System (ISS) stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high- and the low-dose arm, median PFS was 44.8 and 33.0 months (HR, 0.65; 95% CI, 0.44-0.97; P = 0.032), 36% and 23% of patients had stringent CR as best response (P = 0.08), and 4-year OS was 79% and 67% (P = 0.16), respectively. Hematologic toxicity, grade ≥3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose adjustments. SPM incidence and quality-of-life (QoL) scores in both arms were similar.
Conclusions
LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent.
Related Questions
How would you approach dose modifications and/or frequency of lenalidomide in patients with advanced renal impairment (eGFR <30)?
Great question - comes up a lot in discussion with community providers. The dosing is dependent on what your target dose would be. If normal dosing was 25 mg and CrCl <30 and not on dialysis, then I follow the package insert "15 mg every other day". If the patient tolerates that ok, I increase to 10...
How do you approach patients with recurrent grade 3+ neutropenia on IMiD-containing regimens (e.g., VRd or KRd) beyond dose reductions?
IMiD dosing is a challenge. Let's start with what we know: The FDA approved dose of thalidomide is out of date and the OPTIMUM trial suggests 100 mg PO qHS is the "best" dose (Kropff et al., PMID 22133776) because 400 mg is far too toxic. The phase 1 of Pomalidomide does not demonstrate superiority ...