Clinical Outcomes and Cost of Outpatient Community-Based Treatment for Rituximab Refractory Non-Hodgkins Lymphoma (NHL) Patients.
Authors: Zelenetz Andrew D. , Tang Boxiong , Frame Diana , Nalysnyk Luba , Cella Catherine , Noel J. Kay 
Published: April 2020

Abstract
Introduction: We examined treatment patterns, clinical outcomes, and cost of treatment for NHL patients refractory to rituximab (no response or duration of less than 6 months) in US community outpatient hematology/oncology practices.
Methods: Patients with an NHL diagnosis receiving antineoplastic treatment after failing rituximab were selected from a de-identified electronic medical record (EMR) database installed at 14 practices in 8 states. Any systemic chemo/immunotherapy regimen starting within 6 months of the end of a rituximab-containing treatment course was eligible for analysis, except rituximab monotherapy which could not be distinguished from maintenance treatment. Treatment-free interval (TFI) was calculated from last day of the post-rituximab regimen until start of the next antineoplastic regimen. Survival was calculated from day 1 of the regimen. Both were censored at the last active visit date if no event was recorded in the EMR at database cut-off (3/31/04). Hematologic toxicities were collected through 30 days after end of treatment, and graded according to NCI criteria. Only patients with at least one relevant lab result (Hb, ANC, platelets) were considered evaluable for hematologic toxicity. Costs were calculated per chemotherapy or supportive care dose administered, using 2004 wholesale average cost and average national rates for chemotherapy infusion.
Results: 235 patient records met all eligibility criteria (59% male, median age 65, median NHL duration 16 months). The treatment regimens commonly observed were alkylator-based (mostly CHOP, CVP), cytarabine-based (mostly ESHAP), and purine analog-based (mostly fludarabine), all with or without rituximab (+/−R). Costs, adverse event rates, median TFI, and survival by treatment category are shown.
Alkylator-based Cytarabine-based Purine analog-based Other −R +R −R +R −R +R * 50% of TFI and 85% of survival observations censored (ongoing observation or loss to follow-up) N 69 39 31 9 36 18 33 Total Outpt Tx Cost (USD) 5709 27720 11256 21905 10885 24043 15205 Chemotherapy cost (USD) 3179 20605 6552 13090 7249 20306 11549 Support care cost (USD) 2530 7115 4704 8815 3636 3737 3656 Cost per TFI month 5709 13200 4169 19914 9895 8587 16894 TFI (mos)* 1.0 2.1 2.7 1.1 1.1 2.8 0.9 Survival (mos)* 6.1 6.9 7.2 8.9 6.4 4.5 2.0 Anemia (% gr 3–4) 18 6 21 50 6 0 12 Neutropenia (% gr 3–4) 55 69 67 50 59 38 50 Thrombocytopenia (% gr 3–4) 25 26 84 75 23 0 36
The cost of supportive care for toxicity (antiemetics, growth factors, and transfusions), excluding hospital cost, was 30% of the total cost of treatment. Hospitalization was 2.5% and is under-reported in this outpatient EMR database. Average cost per TFI month was $10,957.
Conclusions: Many of these rituximab-refractory patients received subsequent antineoplastic regimens within a few weeks of failing treatment (median TFI 1.3 months). Use of rituximab in this setting added to the treatment cost without an appreciable impact on outcome. Toxicity, particularly neutropenia, is a significant cost driver in total costs of treatment. Recent clinical evidence suggests that radioimmunotherapy might be more cost-effective in this population as compared to conventional chemotherapy, based on the ability to produce durable remissions in these patients, resulting in an extended TFI. These potential advantages should be explored further in controlled trials.