Micrograph showing FL
A multidrug regimen can improve upon involved-field radiotherapy (IFRT) in patients with early stage follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.
FL patients who received IFRT plus cyclophosphamide, vincristine, and prednisolone (CVP)—with or without rituximab—had a significant improvement in progression-free survival (PFS) compared to patients who received standard treatment with IFRT alone.
However, there was no significant difference in overall survival (OS) between the treatment arms.
“This is the first successful randomized study ever to be conducted in early stage follicular lymphoma comparing standard therapy to standard therapy plus effective chemotherapy or immunochemotherapy,” said Michael MacManus, MBBCh, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.
“It shows that the initial treatment received by patients can significantly affect their long-term chance of staying free from disease. Moving forward, we are interested in determining whether there is a benefit in overall long-term survival for patients treated with the combination with further follow-up, and if there is any way to predict if a person will benefit from combined treatment based on analyses of blood or biopsy specimens.”
Dr MacManus and his colleagues studied 150 patients with stage I to II, low-grade FL who were enrolled in this trial between 2000 and 2012.
At randomization, the patients’ median age was 57, 52% were male, 75% had stage I disease, and 48% had PET staging.
Half of patients (n=75) were randomized to receive IFRT (30-36 Gy) alone, and half were randomized to IFRT (30-36 Gy) plus 6 cycles of CVP. From 2006 on, patients in the CVP arm received rituximab (R) as well (n=31).
Baseline characteristics were well-balanced between the treatment arms.
Efficacy
The median follow-up was 9.6 years (range, 3.1 to 15.8 years).
PFS was significantly better among patients randomized to receive CVP±R (hazard ratio [HR]=0.57; P=0.033). The estimated 10-year PFS rate was 41% in the IFRT arm and 59% in the CVP±R arm.
Patients randomized to receive CVP plus R (n=31) had significantly better PFS than patients randomized to receive IFRT alone (n=31) over the same time period (HR=0.26; P=0.045).
There were 10 deaths in the IRFT arm and 5 in the CVP±R arm, but there was no significant difference in OS between the arms (HR=0.62; P=0.40). The 10-year OS rate was 86% in the IFRT arm and 95% in the CVP±R arm.
There was no significant between-arm difference in transformation to aggressive lymphoma (P=0.1). Transformation occurred in 10 patients in the IFRT arm and 4 in the CVP±R arm.
Safety
There were 148 patients from both arms who ultimately received IFRT, and 69 patients who received CVP±R.
Grade 2 toxicities occurring in more than 10% of IFRT recipients included upper gastrointestinal (n=27; 18%), skin (n=21; 14%), and mucous membrane (n=19; 12%) toxicity. One IFRT recipient had grade 3 mucositis, and 1 had grade 4 esophageal/pharyngeal mucosal toxicity.
Grade 3 toxicities occurring in at least 2 patients in the CVP±R arm included neutropenia (n=10; 14%), infection (n=8; 12%), diarrhea (n=3; 4%), elevated gamma-glutamyl transferase (n=3; 4%), fatigue (n=3; 4%), and febrile neutropenia (n=3; 4%).
Three patients (4%) in the CVP±R arm had acute grade 3 neuropathy related to vincristine. Ten patients (14%) had grade 4 neutropenia.
The most common late toxicities for the entire patient cohort were salivary gland (n=8; 5%) and skin (n=4; 3%) toxicities.
Grade 3 lung and menopausal toxicities occurred in 1 patient each. Two patients had late grade 3 vincristine neuropathy. One patient who had grade 3 neuropathy during chemotherapy progressed to grade 4.