Clinical trialPhase 3Blood cancers (leukaemia, lymphoma and myeloma)Lymphoma

AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma

JCO · 2019358 patients

Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, et al. JCO. 2019. 37:1188-1199

Study type: Clinical trial
Study name: AUGMENT
Phase: Phase 3
Design: Randomised multicentre trial, lenalidomide plus rituximab versus placebo plus rituximab
Sample size: 358 patients
Source: JCO · 2019

In plain words

In this study, patients with some types of slow-growing lymphoma (follicular and marginal zone) whose disease had come back or had not responded to treatment were given either rituximab with lenalidomide or rituximab with a placebo (dummy pill). Adding lenalidomide kept the disease from getting worse for much longer (median 39.4 months versus 14.1 months). On the other hand, infections, low white blood cell counts (neutropenia) and skin reactions were more common in the lenalidomide group.

Key results

0.46 (95% CI 0.34 to 0.62)

Progression-free survival (hazard ratio)

P<0.001

39.4 months vs 14.1 months

Median PFS

Lenalidomide + rituximab versus placebo + rituximab; 95% CI: 22.9 months to not reached vs 11.4 to 16.7 months

Drugs in this study:Lenalidomide (Revlimid)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Lenalidomide + rituximab (R2; AUGMENT trial)

Relapsed/refractory follicular lymphoma (grade 1 to 3a) or marginal zone lymphoma after at least one prior therapy, not refractory to rituximabCycle length: Every 28 daysOn the page “Lymphoma” · Treatment regimens and dosing: follicular lymphoma

Relapsed/refractory follicular lymphoma (grade 1 to 3a) or marginal zone lymphoma after at least one prior therapy, not refractory to rituximab

Drug	Dose	Route	Schedule
Lenalidomide	20 mg daily (creatinine clearance 30 to 59 mL/min: 10 mg)	Oral	Days 1–21
Rituximab	375 mg/m²	IV	Cycle 1: Days 1, 8, 15 and 22; cycles 2–5: Day 1

Cycle length: Every 28 days
Duration: 12 cycles of lenalidomide (rituximab in the first 5 cycles)

Doses from the full text of AUGMENT. Anticoagulant or antiplatelet prophylaxis was recommended for patients at risk of thromboembolism; growth factor use was permitted according to guidelines. Per the label, after recovery from cytopenia the dose is reduced by 5 mg (not below 5 mg); with creatinine clearance of 30 to 60 mL/min, an increase to 15 mg is possible after 2 cycles if tolerated.

On the page “Lymphoma” · Treatment regimens and dosing: follicular lymphoma

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 + rituximab (178 patients)

Lenalidomide 20 mg orally daily on days 1 to 21 (creatinine clearance 30 to 59 mL/min: 10 mg), every 28 days for 12 cycles, plus rituximab 375 mg/m² IV on days 1, 8, 15 and 22 of cycle 1 and day 1 of cycles 2 to 5. Lenalidomide dose reductions were planned for toxicity management; in patients at risk of thromboembolism, anticoagulant or antiplatelet prophylaxis was recommended at the investigator's discretion; growth factors were allowed per ASCO/ESMO guidelines.

2Placebo + rituximab (180 patients)

Placebo on days 1 to 21 every 28 days for 12 cycles, plus rituximab at the same dose and schedule (375 mg/m², weekly in cycle 1 and day 1 of cycles 2 to 5).

Source of the regimen details: Full text of the paper in PMC (PMC7035866), Methods section

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 follicular lymphoma (grade 1 to 3a) or marginal zone lymphoma requiring treatment, with at least one prior therapy (chemotherapy, immunotherapy or chemoimmunotherapy) and at least two prior doses of rituximab, with relapsed, refractory or progressive disease that was not rituximab-refractory. Patients with neuropathy above grade 1 were excluded. 82% had follicular lymphoma and 18% marginal zone lymphoma; median age 63 years.

Endpoints

Primary endpoint: progression-free survival (PFS) by independent radiological review.

Safety and side effects

Infections (63% versus 49%), neutropenia (58% versus 23%) and cutaneous reactions (32% versus 12%) were more common in the lenalidomide + rituximab group. Grade 3 or 4 neutropenia (50% versus 13%) and grade 3 or 4 leucopenia (7% versus 2%) were more frequent in the lenalidomide + rituximab group. No other grade 3 or 4 adverse event differed by 5% or more between the two groups.

Clinical significance and place in guidelines

According to the abstract, adding lenalidomide to rituximab in relapsed/refractory follicular or marginal zone lymphoma significantly improved progression-free survival compared with rituximab alone, with an acceptable safety profile reported. The status of drug approvals and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.

Limitations

The abstract gives no information on overall survival, response or other secondary endpoints. Grade 3 or 4 neutropenia was markedly more frequent in the lenalidomide group. Other limitations should be checked in the full text.

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.