Anti CD-20 Radioimmunotherapy (RIT) Can Be Safely and Effectively Delivered in a Community-Based Hospital

Abstract 4991

Anti-CD20 RIT is the most effective single agent treatment for B-cell lymphoma. However, it is not widely used in community-based oncology because of perceived complexity of treatment and toxicity. We analyzed the first 48 patients treated with RIT at our institution between November 2003 and February 2011. A work sheet for referral, screening and treatment process was developed jointly between Oncology and Nuclear Medicine and a mid-level provider (MM) was designated as RIT coordinator. Pre-treatment evaluation of all patients was according to recent consensus conference report on RIT (Witzig T et al 2011) including pretreatment imaging and bone marrow (BM) aspiration and biopsy. Unless dictated by patient's renal function, bladder control status and ability to comply with post treatment radiation safety requirement, the type of RIT (Ibritumomab Tiuxetan [Zevalin®] or Iodine 131 Tositumomab [Bexxar®]) was up to the discretion of referring oncologist. For Bexxar-treated patients, dosimetry imaging was done at 48 and 120 hours; Therapy dose, on day 8, was calculated to deliver 75 cGy to the total body. Zevalin imaging (In-111) was done at 48h and therapeutic dose of 0.4mCi/kg or 0.3mCi/kg depending on platelet counts (≥150K/μL or 100–149K/ μL, respectively) on days 7, 8, or 9. Patients were monitored for toxicity (NCI-CTC v4.03) and evaluated for response after 12 weeks of therapy according to Revised Response Criteria for Malignant Lymphoma (Cheson BD et al 2007). The SPSS v19.0 program was used for statistical analysis. Median age for the whole group was 60 at diagnosis (range 34–88) and 68.5 (37-89) at RIT. There were 19 males and 29 females. All patients, except one, had relapsed or refractory disease. Twenty two patients had diffuse large B-cell lymphoma (DLBCL) and 25 had follicular lymphoma (FL) with or without transformation. Thirty four patients were treated with Bexxar and 14 were treated with Zevalin. Thirty three of 45 evaluable patients for response achieved complete (CR n=20, 44%) or partial (PR, n=13, 29%) response for overall response rate (ORR) of 73%. There was lower, but statistically not significant, ORR for DLBCL (65%) compared with FL (79%). Other factors that did not influence ORR were race, gender, type of RIT, stage of disease and BM involvement by lymphoma. There was a trend towards association between IPI score and response in DLBCL (100% ORR for scores 0–1 vs 40% for score 3). FLIPI, however, was not predictive due to the high ORR in FL. Prior therapy and response to last regimen prior to RIT (LRPtoRIT) was predictive of ORR. 100%, 79% and 47% of patients who received 1, 2, ≥3 prior regimens responded to RIT, respectively (P 0.01). 84% of patients who achieved CR or PR to LRPtoRIT responded to RIT compared with 44% of those who did not respond to LRPtoRIT (P 0.014). 87% of patients who did not receive prior external beam radiation (RT) responded to RIT compared with 43% in those who were previously treated with RT (P 0.002). Finally, patients ≤60 years of age had higher response (93%) compared with those >60 (65%) (P 0.047). Multivariate analysis showed that response to LRPtoRIT was still significant even after adjusting for age and RT prior to RIT. From Kaplan-Meier analysis, the median survival of the whole group was 48 months; 39 months for DLBCL and 82 months for FL (P 0.096). Patients who responded to RIT had a median survival of 81 months compared with those who did not (4.2 months) (P 0.000). Other factors that predicted for survival in univariate analysis were: number of prior regimens (P 0.017), response to LRPtoRIT (P 0.001), and prior external beam radiation (P 0.024). In multivariate analysis, response to RIT and response to LRPtoRIT were significant predictors of survival (P 0.048 and 0.026, respectively). There were no treatment-related deaths. Grade 3/4 toxicity was only hematologic including thrombocytopenia (38%), neutropenia (31%) and anemia (12.5%). Median time to nadir was 5, 6 and 8 weeks post therapy for platelets, neutrophils and hemoglobin, respectively. Two patients developed secondary AML and one patient developed MDS, all with complex chromosomal abnormalities. We conclude that with coordinated effort, RIT can be safely and effectively delivered in routine community setting with results comparable to those reported in clinical trials. Prior therapy and response to LRPtoRIT predict response to RIT whereas response to RIT and response to LRPtoRIT are predictive of overall survival.