Abstract

Sequential treatment with chemotherapy and radioimmunotherapy (RIT) results in overall response rates > 90% in untreated follicular lymphoma (FL). We previously reported a complete response rate (CR) of 89% in 60 patients with stage II–IV symptomatic or bulky FL who received a short-course CHOP-Rituximab (R) x 3 cycles followed by Ibritumomab Tiuxetan (IT) and extended R as first-line treatment in Clinical Cancer Research (in press). This report will update the CR and progression-free survival (PFS) at a median follow-up of 27.1 months (range 0.9–46.1 months). Determination of response and duration of response included a fusion [18 F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging performed at baseline, after the third cycle of CHOP-R, 12 weeks after RIT, then at 6-month intervals for the first three years, and then yearly or at physicians’ discretion. Of the 60 enrolled patients, 55 completed all protocol therapy. The continuous CR rate for all enrolled patients by PET-CT is 73%. The median PFS for all enrolled patients is 38.3 months. To date, 11(18%) patients have relapsed at 7.8–38.3 months. Ten of 11 relapses were among the 35 patients who had positive bone marrow biopsies (28.6%) compared to 1 relapse among the 25 (4.0%) with negative biopsies. Eight of 18 patients with a positive PET scan after CHOP-R have relapsed compared to only 3 relapses of 37 patients with a negative PET scan after CHOP-R. Nine of 10 available relapse tissue biopsies showed FL, and one showed transformation to a diffuse large B-cell lymphoma. Seven patients have been diagnosed with a second malignancy: 1 uterine cancer, 1 colon cancer, 1 prostate cancer, 1 breast cancer, 1 lung cancer, 1 pancreatic cancer, and 1 T-cell lymphoma. There have not been any cases of myelodysplastic syndrome or acute myeloid leukemia. Conclusions: Short course CHOP-R followed by IT and extended R results in high CR rate. However, despite achieving a CR after IT, positive bone marrow involvement at baseline (p<0.001) and residual PET positivity after 3 cycles of CHOP-R (p=0.003) were predictive of early relapse. These predictors of early relapse may be utilized in the design of future clinical trials.

Relapsed Patient Grade Stage Flipi Risk Bulk (cm) Bone Marrow Pet Post CHOP Pet Post RIT Time (months) to Progression Relapse Biopsy 
IV 3.4 Pos Neg 13.5 Follicular 
IV 5.8 Pos Neg 21.8 Follicular 
IV 14 Pos Neg 31.2 Follicular 
IV 13.5 Pos Pos 7.8 Follicular 
III 7.1 – Pos Neg 38.3 Follicular 
IV 4.8 Neg Neg 27.8 Follicular 
IV Neg Neg 17.2 Follicular 
N/A IV 4.2 Neg Neg 20.0 N/A 
IV 7.4 Pos Pos 13.6 Large Cell 
10 IV Pos Neg 14.0 Follicular 
11 IV 3.8 Pos Neg 9.3 Follicular 
Relapsed Patient Grade Stage Flipi Risk Bulk (cm) Bone Marrow Pet Post CHOP Pet Post RIT Time (months) to Progression Relapse Biopsy 
IV 3.4 Pos Neg 13.5 Follicular 
IV 5.8 Pos Neg 21.8 Follicular 
IV 14 Pos Neg 31.2 Follicular 
IV 13.5 Pos Pos 7.8 Follicular 
III 7.1 – Pos Neg 38.3 Follicular 
IV 4.8 Neg Neg 27.8 Follicular 
IV Neg Neg 17.2 Follicular 
N/A IV 4.2 Neg Neg 20.0 N/A 
IV 7.4 Pos Pos 13.6 Large Cell 
10 IV Pos Neg 14.0 Follicular 
11 IV 3.8 Pos Neg 9.3 Follicular 

Disclosures: Jacobs:Biogen Idec: Research Funding. Off Label Use: Ibritumomab Tiuxetan is currently off-label for use in front-line setting for follicular lymphoma. It is approved for relpased/ refractory disease..

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