Radioimmunotherapy: A New Treatment Modality for B-Cell Non-Hodgkin’s Lymphoma

May 1, 2004

Despite the remarkable resultsso ably described by Ghobrialand Witzig in this issue ofONCOLOGY, radioimmunotherapyfor low-grade and transformed lowgradelymphoma is a treatment thatappears to be currently underutilizedby clinicians. The two US Food andDrug Administration (FDA)-approvedanti-CD20 radiolabeled antibodies,Y-90 ibritumomab tiuxetan (Zevalin)and tositumomab/iodine-131 (I-131)tositumomab (Bexxar), have producedresponse rates from 50% to 80% andcomplete response rates from 20% to40% in studies of patients with varyingresistance to chemotherapy as wellas rituximab (Rituxan), making theseagents probably the most active systemicagents we have available forlow-grade B-cell lymphoma.

Despite the remarkable resultsso ably described by Ghobrialand Witzig in this issue ofONCOLOGY, radioimmunotherapyfor low-grade and transformed lowgradelymphoma is a treatment thatappears to be currently underutilizedby clinicians. The two US Food andDrug Administration (FDA)-approvedanti-CD20 radiolabeled antibodies,Y-90 ibritumomab tiuxetan (Zevalin)and tositumomab/iodine-131 (I-131)tositumomab (Bexxar), have producedresponse rates from 50% to 80% andcomplete response rates from 20% to40% in studies of patients with varyingresistance to chemotherapy as wellas rituximab (Rituxan), making theseagents probably the most active systemicagents we have available forlow-grade B-cell lymphoma.And although the title of the reviewpresented by Ghobrial and Witzig suggeststhat radioimmunotherapy is a newmodality for the treatment of non-Hodgkin's lymphoma, the follow-upof patients treated with tositumomab/I-131 tositumomab, for instance, extendsfor over a decade. Thus, there isample evidence concerning durabilityof responses as well as long-term consequencesof this type of treatment.Timing of Therapy
The optimal time for the use ofradioimmunotherapy in a patient'streatment history has not been definitivelyestablished. So far, it has beenused mostly as salvage after chemotherapyand rituximab have failed.However, there is mounting evidenceto support its use earlier in the courseof disease. Most telling is the 95%overall and 75% complete responserates when tositumomab/I-131 tostitumomabwas used as frontline therapyfor follicular lymphoma. Theresults with radioimmunotherapy beingused as consolidative treatmentafter chemotherapy in the frontlinesetting are also supportive. Approximately80% of patients are predictedto remain disease-free at 2 years.Moreover, the durability of responses,especially complete responses-evenin chemotherapy- and rituximabrefractorypatients-needs to be recognized.Up to 30% of patients withpreviously treated disease may haveremissions lasting years.With additional experience overthe years, there is now less concernabout "burning bridges" or reducingthe ability to treat patients who relapseafter radioimmunotherapy. Indeed,patients can be effectively andsafely re-treated with radioimmunotherapyin addition to receiving rituximab,chemotherapy, and evenhematopoietic stem cell transplantation.Although myelodysplasia andacute myeloid leukemia have beenreported after radioimmunotherapy,this has so far only been observed inheavily pretreated patients who werealready at risk for developing thisproblem. With extended follow-up ofalmost 5 years, no such cases havebeen observed in patients who havereceived radioimmunotherapy as afrontline regimen.Toxicity and Convenience
In weighing options for patients,toxicity and convenience need to beconsidered. In contrast to chemotherapy,which involves multiple treatments(and therefore repetitive, andpossibly, cumulative risks) for severalmonths, the administration of thetwo approved radioimmunotherapeuticagents can be accomplished in1 week without any repetitive cycles.Although hematologic nadirs can bedeep and prolonged, they rarely resultin a need for clinical interventionsuch as transfusions, growth factorsupport, or hospitalization for neutropenicfevers. Patients often remark onboth the lack of toxicity and the convenienceof this treatment, comparedto what they had previously experiencedwith chemotherapy.One of the perceived barriers towidespread acceptance of this therapyis the coordination needed amongthe ordering hematologist/oncologist,nuclear medicine/radiation oncologyphysician/staff, nuclear pharmacy, andnursing. Indeed, this treatment isunique in its multidisciplinary natureamong existing therapies. However,once a system is in place, administrationof the therapy can become asmooth and efficient operation.Conclusions
As Ghobrial and Witzig suggest,we have yet to fully explore the potentialof radioimmunotherapy forlymphoma. This also extends to itsuse in histologies other than the lowgradeB-cell lymphomas. With thenumber of potential agents becomingavailable, questions about choicesamong these agents (including thosedirected against the same antigen)need to be answered. As is so oftenthe case, we learn more about how atherapy can be used after FDA approvalthan before. Nevertheless, ourknowledge will come from prospectiveclinical trials, in which physiciansand patients should beencouraged to participate.

Disclosures:

The author receivesresearch grants and royalties from Corixa Corporation,and is a member of the Speaker’sBureau and receives royalties from Glaxo-SmithKline.