Clinical trialLymphoma

Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study.

J Clin Oncol · 20191018 patients randomised (505 rituximab maintenance, 513 observation); 607 in extended follow-up

Bachy E, Seymour JF, Feugier P, et al. J Clin Oncol. 2019. 37:2815-2824

Study type: Clinical trial
Study name: PRIMA
Design: Randomised (1:1) maintenance trial after non-randomised immunochemotherapy induction; final report with 9 years of follow-up
Sample size: 1018 patients randomised (505 rituximab maintenance, 513 observation); 607 in extended follow-up
Source: J Clin Oncol · 2019
Trial registration: NCT00140582

In plain words

In follicular lymphoma, after the first course of treatment (immunochemotherapy), rituximab can be given as an injection every 2 months for 2 years to delay the disease coming back. This final report, with about 9 years of follow-up, showed that this maintenance treatment lengthened the average time without the disease getting worse from about 4 years to about 10 and a half years, but it did not change how long people lived; about 80% of patients in both groups were alive after 10 years. Make the decision about maintenance treatment with your doctor, weighing the benefits and side effects.

Key results

10.5 years vs 4.1 years

Median progression-free survival

HR 0.61 (95% CI 0.52–0.73); P<.001

No difference

Overall survival

HR 1.04 (95% CI 0.77–1.40); P=.7948

About 80% in both groups

10-year overall survival

Drugs in this study:Rituximab (Rituxan/MabThera)

Dose and schedule cards

Rituximab maintenance (PRIMA trial) and single-agent rituximab

Maintenance: follicular lymphoma with a high tumour burden that has achieved a complete or partial response to induction immunochemotherapy; single agent: asymptomatic follicular lymphoma with a low tumour burdenOn the page “Lymphoma” · Treatment regimens and dosing: follicular lymphoma

Drug	Dose	Route	Schedule
Maintenance
Rituximab	375 mg/m²	IV	Every 8 weeks, starting 8 weeks after the last induction cycle
Single agent
Rituximab	375 mg/m²	IV	Weekly for 4 weeks

Cycle length: Maintenance: every 8 weeks
Duration: Maintenance: 2 years (12 doses); single agent: 4 weekly doses, with or without 12 maintenance infusions every 2 months for 2 years

Maintenance from PRIMA and the FDA label. Single-agent rituximab in asymptomatic low-volume lymphoma from the British trial; this treatment only delayed the time until new treatment was needed. Active surveillance is also a standard approach for these patients.

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

Niraparib maintenance (PRIMA)

Advanced disease with complete or partial response to first-line platinum; current FDA label: HRD-positive only; ESMO: can also be considered in HRD-negative disease [I, B]Cycle length: ContinuousOn the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

Advanced disease with complete or partial response to first-line platinum; current FDA label: HRD-positive only; ESMO: can also be considered in HRD-negative disease [I, B]

Drug	Dose	Route	Schedule
Niraparib	Weight less than 77 kg or platelets less than 150,000: 200 mg; weight 77 kg or more and platelets 150,000 or more: 300 mg	Oral, once daily (taking it at bedtime helps reduce nausea)	Continuously

Cycle length: Continuous
Duration: Start no later than 12 weeks after the last platinum dose; label: until progression or toxicity; ESMO: 3 years

Monitoring: complete blood count weekly for the first month, monthly for the next 11 months and periodically thereafter; blood pressure and heart rate at least weekly for the first 2 months, then monthly for the first year. Platelets below 100,000: withhold for up to 28 days with weekly blood counts. Dose reduction: 200 → 100 mg; 300 → 200 → 100 mg; moderate hepatic impairment: 200 mg. In PRIMA, overall survival did not differ (HR 1.01).

On the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

Previously untreated follicular lymphoma: with chemotherapy, then maintenance

Previously untreated CD20-positive follicular lymphomaOn the page “Rituximab (Rituxan/MabThera)” · Combination regimens and the subcutaneous form (FDA label)

Previously untreated CD20-positive follicular lymphoma

Drug	Dose	Route	Schedule
Induction
Rituximab	375 mg/m²	IV infusion (rate as in the prescribing notes)	Day 1 of each chemotherapy cycle
Maintenance (in complete or partial response)
Rituximab	375 mg/m²	IV infusion (rate as in the prescribing notes)	Every 8 weeks

Cycle length: As per the chemotherapy regimen; then every 8 weeks
Duration: Induction up to 8 doses; maintenance 12 doses starting 8 weeks after the end of induction

On the page “Rituximab (Rituxan/MabThera)” · Combination regimens and the subcutaneous form (FDA label)

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

1Rituximab maintenance

After induction with one of three common chemoimmunotherapy regimens with rituximab (non-randomised), rituximab 375 mg/m² IV every 8 weeks for 2 years (up to 12 doses), starting 8 weeks after the last induction treatment. Induction regimen doses are in the full text of the paper.

2Observation

No further treatment after induction.

Source of the regimen details: Abstract of the paper in PubMed and the FDA label for RITUXAN (maintenance every 8 weeks for up to 12 doses); induction regimen doses 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 older than 18 with previously untreated high tumour burden follicular lymphoma who had responded to one of three induction immunochemotherapy regimens.

Endpoints

Final report of progression-free survival and overall survival after 9 years of follow-up and final safety review (primary outcome of the PRIMA study: progression-free survival).

Safety and side effects

No new safety signal was seen in long-term follow-up. Details of adverse events are in the full text of the paper.

Clinical significance and place in guidelines

This report showed that the progression-free survival benefit of rituximab maintenance is sustained after about 9 years, but it does not improve overall survival; maintenance therapy is therefore an option to delay relapse, and the decision should be individualised.

Limitations

Only 59.6% of patients consented to extended follow-up; induction regimens were chosen non-randomly. Subsequent treatments after relapse may have affected the overall survival comparison; details of these treatments are not reported in the abstract.

Original article (DOI)PubMed ClinicalTrials.gov

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.