Meta-analysisBlood cancers (leukaemia, lymphoma and myeloma)Multiple myeloma

Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis

JCO · 20171,208 patients (605 in the lenalidomide group and 603 in the placebo or observation group)

McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, et al. JCO. 2017. 35:3279-3289

Study type: Meta-analysis
Design: Meta-analysis of individual patient data from three randomised trials
Sample size: 1,208 patients (605 in the lenalidomide group and 603 in the placebo or observation group)
Source: JCO · 2017

In plain words

This study combined the data of three large trials in people with multiple myeloma who had received a transplant of their own stem cells. Taking a drug called lenalidomide after the transplant kept the disease from progressing for much longer (about 52.8 months versus 23.5 months) and patients also lived longer. At the same time, the chance of a second cancer was higher in those taking the drug, so the decision should be made with the treating doctor after weighing the benefits and harms.

Key results

52.8 vs 23.5 months

Median progression-free survival (PFS)

HR 0.48; 95% CI 0.41–0.55

Not yet reached in the lenalidomide group vs 86.0 months in the placebo/observation group

Median overall survival (OS)

HR 0.75; 95% CI 0.63–0.90; P = 0.001; median follow-up 79.5 months for surviving patients

Higher cumulative incidence with lenalidomide than with placebo/observation

Second primary malignancy before disease progression

Exact figure not reported in the abstract

Higher cumulative incidence in the placebo/observation group than with lenalidomide

Progression, death and myeloma-related death

Exact figure not reported in the abstract

Drugs in this study:Lenalidomide (Revlimid)

Dose and schedule cards

Lenalidomide maintenance after autologous transplantation

After autologous transplantation, once haematologic recovery has occurred (neutrophils at least 1,000/mcL and/or platelets at least 75,000/mcL)Cycle length: Every 28 daysOn the page “Multiple myeloma” · Newly diagnosed myeloma: transplant-eligible patients

After autologous transplantation, once haematologic recovery has occurred (neutrophils at least 1,000/mcL and/or platelets at least 75,000/mcL)

Drug	Dose	Route	Schedule
Lenalidomide	10 mg once daily; after 3 cycles, 15 mg if tolerated	Oral	Days 1–28 (continuous)

Cycle length: Every 28 days
Duration: Until disease progression or unacceptable toxicity

Dose and renal adjustment from the FDA label: CrCl 30–60 mL/min: 5 mg once daily; below 30 (not on dialysis): 2.5 mg once daily; dialysis: 2.5 mg after dialysis. In the meta-analysis, the risk of second primary malignancies was slightly higher with maintenance.

On the page “Multiple myeloma” · Newly diagnosed myeloma: transplant-eligible patients

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Lenalidomide maintenance

Lenalidomide as maintenance therapy after ASCT (605 patients). Dose details in the full text of the paper.

2Placebo or observation

Placebo or observation after ASCT (603 patients). Dose details in the full text of the paper.

Source of the regimen details: Abstract of the paper; the lenalidomide maintenance dose differed in each of the three trials and is given in the full text of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with newly diagnosed multiple myeloma (NDMM) who received maintenance with lenalidomide or placebo/observation after autologous stem-cell transplantation (ASCT). Criteria for including trials in the meta-analysis: randomised trial in NDMM patients who had received ASCT followed by lenalidomide maintenance versus placebo or observation, with access to individual patient data and a locked database for the primary efficacy analysis. Three trials were included: CALGB 100104, GIMEMA RV-MM-PI-209 and IFM 2005-02.

Endpoints

In all three trials the primary endpoint was progression-free survival (PFS), and none was powered for overall survival (OS) as a primary endpoint. This meta-analysis was performed to better assess the effect of lenalidomide maintenance. Overall survival, the cumulative incidence of second primary malignancy before disease progression, progression, death and myeloma-related death were also examined.

Safety and side effects

The cumulative incidence of second primary malignancy before disease progression was higher in the lenalidomide maintenance group than in the placebo or observation group. Other safety information (such as grade ≥3 adverse events) is not given in the abstract.

Clinical significance and place in guidelines

This meta-analysis showed that lenalidomide maintenance after ASCT, besides improving PFS, is associated with an overall survival benefit, and therefore supports its use in NDMM patients after transplantation. The increased risk of second primary malignancy should be considered in decision-making and patient monitoring. The status of this recommendation in current guidelines should be checked separately, because the abstract does not mention it.

Limitations

Based on the abstract: in the included trials PFS was the primary endpoint and none was powered for OS. The control group was a mix of placebo and observation. Detailed safety data and drug dose are not reported in the abstract. Other limitations should be checked in the full text of the paper.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.