MAINTENANCE THERAPY WITH LENALIDOMIDE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: A POST-HOC ANALYSIS OF THE EMN01 TRIAL

Background
Lenalidomide maintenance showed to be effective in terms of progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) ≥ 65 years or not eligible for autologous stem cell transplantation. Recently, the geriatric assessment has emerged as a fundamental strategy to evaluate patients’ frailty and consequently to select the most appropriate treatment for elderly MM patients [Palumbo A, et al. Blood. 2015]. 

Aims
In a post-hoc analysis, we classified patients enrolled in the EMN01 trial according to the new geriatric assessment in order to evaluate safety and efficacy of Lenalidomide-containing maintenance in fit, unfit and frail NDMM patients.

Methods

In the EMN01 phase III trial, patients with NDMM were randomized to receive induction treatment with Lenalidomide-dexamethasone or Melphalan-Prednisone-Lenalidomide or Cyclophosphamide-Prednisone-Lenalidomide. After induction, patients were randomized to receive maintenance with Lenalidomide alone (10 mg on days 1-21 in 28-day cycles) or plus Prednisone (25 mg every other day in 28-day cycles), until disease progression or intolerance. The geriatric assessment was performed and included age, comorbidities (according to Charlson Comorbidity index), Activity of daily living and Instrumental Activity of  Daily Living scores. 

Results

Six-hundred-forty-three patients started induction treatment. Patients were classified as fit (n=280), unfit (n=202) and frail (n=161). During induction, 30 patients (11%)  discontinued treatment due to adverse events (AEs) in the fit group and 38 patients (23%) in the frail group (p=0.0006). Deaths not related to progressive disease were 4 in the fit group (mainly due to stroke [n=2]) and 17 in the frail group (mainly due to cardiologic AEs [n=7] and infections [n=3]). Four-hundred-two patients started maintenance treatment: 192 in the fit, 121 in the unfit, and 89 in the frail groups. During maintenance, at least one grade ≥ 3 hematologic AE was reported in 24 patients (13%) in the fit and 13 patients (15%) in the frail groups. At least one grade ≥ 3 non-hematologic AE was recorded in 12 patients (6%) in the fit and 12 patients (13%) in the frail groups (p=0.04), and were mainly cardiologic AEs and infections. After a median follow-up of 30 months since the beginning of maintenance, median PFS was 24 months in fit and 27 months in frail patients (HR= 1.136, CI 0.808-1.596, p=0.464). Median overall survival (OS) was not reached; at 24 months, OS was 90% in fit and 76% in frail patients (HR 2.804, CI 1.665-4.723, p=0.0001). In the frail group, 101 patients (63%) did not reduce any drug doses during induction, and 49 (49%) of them started maintenance; whereas 60 patients (37%) reduced drug doses during induction, and 40 (67%) of them started maintenance. The difference between the two groups of frail patients who began maintenance was statistically significant (P=0.02). 

Summary

The benefit of maintenance therapy in frail patients is controversial. Frail patients who reduced doses at induction tolerated therapy better and had a higher probability to start maintenance. Therefore, an induction treatment tailored to the frailty status allows a higher number of patients to complete induction, and to start and benefit from lenalidomide maintenance.  

Keyword(s): Elderly, Imids, Maintenance, Multiple myeloma

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