Two  anti CD-20 radioantibody therapies: Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositutumomab (Bexxar) were approved in the US in the early 2000s. The  safety and efficacy of both Bexxar and Zevalin were proven relative to rituximab.   While Zevalin remains on the market, sales are reportedly low .  Bexxar exited the market in 2014 after low sales.  Bexxar  cost $26K USD ,  “very expensive” by early 21 st century standards, but  low compared to cancer therapies in 2016. The challenges with  Bexxar  in the US marketplace occurred at a time when  private practice oncologists received the majority of their compensation from the mark up of drug prices between the wholesale and retail prices.  Oncologists could prescribe rituximab at an infusion center, making  money on every patient  they treated.   Prescribing radioimmunotherapy  meant they’d lose that revenue stream.     In addition ,  there were logistical issues with radiopharmaceutical therapy, notably Bexxar, which had “personalized dosimetry  and challenges related  to use I-131 as an inpatient in many locales.   Other issues included US Medicare paying less than the cost of the dosimetric or therapeutic agent and a logistical arrangement which paid none of the providers much for their time.   Both Bexxar and Zevalin have suffered from having multiple commercial owners of the key technology. Oncologists also had concerns of patients developing myelodysplastic syndromes, which could be fatal.  In time, other therapies emerged, while the RIT were mainly static in their technologies such as Bendamustine and idelalisib.

A  trial comparing 554 patients randomized  to chemotherapy + rituximab or chemotherapy + Bexxar showed comparable outcomes.  Bendamustine + ritiuximab appears to be even more effective.   Zevalin remains available, as well as I-131 rituximab in Australia, but both are  “underutilized” relative to their efficacy .   Lessons from these agents should serve to inform and caution the theranostics community.  Theranostic agents need to “work” in the disease  and “work” in the marketplace to succeed.