CHOP-Rituximab-Interferon Therapy in Follicular Lmphoma (FL): High Remissions with Reasonable Toxicity.

Background: Rituximab (R) plus chemotherapy (CTP) results in highly durable remissions in FL. IFN-α-2b has activity against FL and may demonstrate synergism when given concurrently with CTP. Some studies showed clinical benefit to adding IFN to CTP concurrently or as maintenance. We hypothesized that adding IFN to RCHOP may enhance the anti-lymphoma effect via enhancing the ADCC effect of R by generating effector NK and T-cells.

Methods: pts ages ≤75, stages II-IV, classified as B, C and D on IWF were enrolled.

Treatment: 6 cycles of CHOP with R added prior to cycles 1, 3 and 5. Growth factor support was allowed. IFN at 3× 106 U TIW SQ was concurrently given. Subsequently, 4 weekly R doses were given followed by 1 year of maintenance IFN at 5× 10⁶ U TIW SQ for a total of 80 wks of therapy.

Results: 15 pts were enrolled. 1 pt with MZL was taken off study. Among 14 pts with FL, there were 8 males and 6 females. 10 pts were stage IV, 4 stage III, 3 had PS of 0, 9 PS of 1, and 1 PS of 2. Age was 29 to 72 (median 62). 11/14 achieved CR, 2 had PR. At median f/u of 62 mo (36–67), 10/14 pts remain alive and progression-free, including 1 pt with PR who later developed ovarian ca. 2 died of PD, 1 at 13 months after stopping therapy, and the other of CNS transformation during CTP. 1 patient had molecular progression while in clinical CR, responding to additional R and 1 was lost to follow-up. At diagnosis, 8 showed bcl-2 translocation by PCR in BM. AT week 29, 6 of the 8 showed disappearance of the bcl-2 translocation while 1 (who had PR) had persistence of the translocation. 7 completed maintenance; 5 withdrew during maintenance due to IFN toxicity. Grade 3–4 toxicities, included fatigue in 3 pts, neutropenic fever in 2 patients, sensory neuropathy in 1 patient, rash in 1 pt and depression in 1 pt.

Conclusions: treatment of FL with RCHOP plus IFN was reasonably tolerated with high durable responses. Five of 12 pts had to discontinue IFN in the maintenance phase due to toxicity.