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Treatment Overview > Radioimmunotherapy (RIT)

Last update: 12/14/2018

In the News  | What is RIT? | RIT abstracts | Goal of treatment | Clinical Trials |
Potential Benefits and Risks  | Outcome Reports - Consolidation with RIT
Potential contraindications | Bulky disease and RIT?Unique Properties of RIT
 When to consider RIT?RIT for Elderly?  | Centers that Administer RIT  | Zevalin
TOPIC SEARCH:  Review | Zevalin
| Other RIT Agents

2016, June: Rationale for continued study of Radioimmunotherapy

Catch 22:


What is radio-immunotherapy (RIT)?  

When your body detects something that does not belong, such as bacteria (pathogen), one way it eliminates the threat is to produce antibodies that bind to the protein shapes that are specific to the pathogen. 

RIT agents are man-made antibodies with different radiation components attached.  These antibodies are designed to bind to a protein shape called CD20, which sticks out of mature B lymphocytes (immune cells), both malignant and nonmalignant (cancerous and normal).  ... 

...  Importantly, the cd20 shape (or antigen / receptor) is not found on precursor B cells - immature b-cells which can later mature to replenish the supply of normal mature b-cells. 

RIT is considered a targeted therapy, because the antibodies that deliver the radiation are specific to one type of cell.  RIT is more potent than unlabeled antibody therapy, such as Rituxan, but it also has unique potential risks. 

Importantly, there is clinical data showing that RIT is very potent and can induce complete responses that are very durable (measured in years), even in heavily pretreated patients. (See RIT abstracts below.)

RIT is given in therapeutic steps 

(1) The initial antibody dose ("cold" or "naked" antibody) clears the body of normal b-cells so that subsequent doses will be more focused on tumor cells.  

(2) The second "warm" dose has anti-tumor effects, but also helps calculate the optimal final dose based on uptake of the drug and individual clearance rates as determined by imaging of the gamma radioactive element. 

(3) The final "hot" dose has has the most potent anti-tumor effects, and is focused on tumor cells, because prior doses have cleared the body of normal b-cells. 

Unique properties of RIT 

  - Zevalin is an FDA approved RIT for indolent lymphoma
  - RIT has unique properties:
      It takes about 1 week to give it, compared to many months of chemotherapy.
      It's the only non-chemotherapy-based approach with a high rate of durable remissions
      It's an important choice for patients:
         - who must continue to work through or shortly after treatment
         - who cannot tolerate chemotherapy, because of advanced age, or specific comorbidities
         - who may prefer to limit the on-treatment side effects specific to chemotherapy
            such as nausea, neuropathy, hair loss, gastric, and gastric and mucositis complications.

Possible mechanisms of action  

When radio-labeled antibody binds to tumor cells it can cause tumor killing by

  1. Apoptosis - programmed cell death triggered by the antibody 

  2. Complement-dependent cytotoxicity (CDC) - where antibody fixes complement that kills the tumor cells

  3. Antibody-dependent cellular cytotoxicity (ADCC) - where effector cells (immune cells) kill the tumor cells

  4. Ionizing radiation from the radioisotope damages the tumor cells, leading to cell death

  5. Vaccine-like effect - leading to adaptive immunity against cells that may survive initial treatment

Other RIT Topics

Approved June 2003
Bexxar vs. Zevalin
Table comparing properties
Approved Feb 2002
Centers that Administer 
Bexxar by State
RIT abstracts | Outcomes
Bulky disease and RIT?
Centers that Administer
Zevalin by State
  Bexxar Treatment 
Site Locator
Other RIT agents?

Zevalin Treatment 
Site Locator

Clinical Trials 

Patient perspectives & questions:
When might RIT be appropriate? 
Goal of treatment and RIT 
Questions for Experts

Clinical Trials

Radioimmunotherapy Background Articles

Dec 2018: Radioimmunotherapy (RIT) for Follicular Lymphoma achieves long term lymphoma control in first line and at relapse: 8-year follow-up data of 281 patients from the international RIT-registry pat 
Radioimmunotherapy with tositumomab and iodine-131 tositumomab for NHL

Radioimmunotherapy of Lymphoma: Ahead of Its Time or Past Its Sell-By Date? 

Tim Martin Illidge, School of Cancer and Imaging Sciences, Manchester Academic Health Sciences, University of Manchester, Manchester, United Kingdom

"As we look to the future, few things are certain, but we can be sure that there will continue to be increasing numbers of patients with follicular lymphoma who are refractory to both chemotherapy and rituximab. For the latter group, there are compelling data that RIT can play an important role in both chemotherapy- and rituximab refractory disease, leading to high response rates with durable remissions."
Radioimmunotherapy review article

"Currently in the United States, RIT is mainly used in the salvage setting; however, emerging data suggest that to enhance patient benefit, RIT should be administered earlier in the treatment of follicular lymphoma. In an analysis of 1,177 patients treated with 131I-tositumomab, the ORR, CR rate, and duration of response decreased as the number of prior therapies increased."
Rationale for Consolidation to Improve Progression-Free Survival in Patients with Non-Hodgkin's Lymphoma: A Review of the Evidence 

"With the higher CR rates and longer Progression Free Survival (PFS) times observed in patients with FL and DLBCL, as well as encouraging early data from MZL and MCL consolidation trials, RIT appears to have an important role in the treatment of patients with NHL."
Radioimmunotherapy for Non-Hodgkin’s Lymphoma 
Arati V. Rao, MD, Gamal Akabani, PhD and David A. Rizzieri, MD
Perspectives on RIT therapy 
Robert M. Sharkey, PhD; and David M. Goldenberg, ScD, MD 
Radioimmunotherapy in the treatment of low grade b-cell lymphoma  ash2003  PDF 
Radioimmunotherapy of Cancer 
Radioimmunotherapy of B-Cell Non-Hodgkin’s Lymphoma: From Clinical Trials to Clinical Practice
Malik E. Juweid, MD
Novel Concepts in Radioimmunotherapy for Non-Hodgkin's Lymphoma
Randomized Controlled Trial of Zevalin Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell NHL 
Multicenter Phase II Study of Bexxar for Chemotherapy-Relapsed/Refractory Low-Grade and Transformed Low-Grade B-Cell NHL

Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies.

Potential Benefits and Risks: RIT Studies:

FDA approved indications for RIT: "for the treatment of relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL)."   

Comparing Risks of RIT-based therapy with Chemo-Rituxan-based therapy?

RIT, like all cancer treatments, has risks which should be carefully considered when making  treatment decisions. 

It should be noted that it's not possible to avoid treatment risk (even delaying therapy has risks) and chemotherapy-based protocols can have risks similar to RIT.  

At present it's not known which approach to treating indolent lymphomas is better (on average) for survival - an endpoint that FDA considers the only reliable measure for comparison because it accounts for both known and unknown positive and adverse effects.  

The risk we take cannot be separated from the potential reward or from clinical necessity. When you sprint to escape an aggressive bear you increase the risk of breaking a leg, or having a cardiac event  ...  Similarly, how appropriate the risks we assume when selecting a therapy depends on the clinical circumstances and the goal of treatment.

Ultimately, only well-controlled studies with sufficient follow up will help to determine which treatment approach provides the better chance for optimal clinical benefit, and most likely - given the variation in the disease and patients - the optimal therapy for any person varies and will involve some chance. 

As the reports below indicate RIT is perhaps the most potent agent we have at this time for indolent b-cell lymphomas, but it also has risks, such as low platelet counts, infections, bleeding, and myelodysplastic syndromes (MDS), and also hypothyroidism for bexxar.  Noting that the latency (time it takes to develop and present) for MDS - a serious potential complication - can be quite long. However, it should be noted that the risk of MDS also exists for chemotherapy-based protocols.

"Two studies have evaluated the risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia following RIT with either 90Y-ibritumomab or 131I-tositumomab. These retrospective analyses of large numbers of patients both showed that RIT did not produce a higher risk for MDS in comparison with similar patient populations treated with multiple chemotherapies alone [90, 91]. MDS has rarely been observed in patients treated upfront with RIT using 131I-tositumomab alone [63].

 - Radiolabeled and Native Antibodies and the Prospect of Cure of  Follicular Lymphoma

See for technical safety information Bexxar | Zevalin

In your conversation with your doctor about risks and benefits, you might also inquire about what future therapies may be precluded (made no longer available) by use of RIT and what specific clinical factors (such as age, areas of involvement, previous therapies) may increase or reduce risk as described in the following technical paper.  

* Prediction of Hematologic Toxicity After Radioimmunotherapy with I-Labeled  

* Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab  for non-Hodgkin lymphoma. Cancer. 2005 Dec 16; PMID: 16362977

* Re-Treatment With I-131 Tositumomab in Patients With Non-Hodgkin's Lymphoma Who Had Previously Responded to I-131 Tositumomab

* Specific Regimen Influences Risk of Myelodysplasia After Lymphoma Treatment  BloodJournal

* Harvesting Stem Cells for Transplant in Non-Hodgkin's Lymphoma Patients Is Still Possible After Treatment with Bexxar

See also Factors that Influence Treatment Decisions

Background:  A  reason RIT is considered a vital therapy is that it is the first treatment proven to reverse the pattern of decreasing response and duration of response in indolent lymphomas. Durable remissions reduce the need for multiple toxic treatments, which have been found by experts* to result in diminished response rate and duration of response. Furthermore, achieving a durable remission can substantially improve quality of life independent of symptoms by reducing  the anxiety associated with living with active or dormant disease - particularly when the improved duration of the remissions is measured in years, suggesting a chance of cure.  

The following abstract describes the pattern of relapse for follicular lymphomas with standard therapy:

* Each Subsequent Therapy Results in Diminishing Response Rate and Duration of  Response in Low Grade or Transformed Low Grade NHL  ASCO 2001  

"Evaluation of response and duration of response in these sixty patients to all prior chemotherapies  re-confirmed the previously published experience showing diminished response and duration of response with each subsequent chemotherapy.

In this same patient population the duration of response to the most recent chemotherapy was 4 months. However, upon relapse, subsequent treatment with Bexxar (a type of RIT) provided a 10 month duration of response (p=<0.001 ). An independent radiology and oncology review panel confirmed these findings. 

The high incidence of multiple relapses and the enduring decrease in both response and duration of response to subsequent therapy further reinforces the need for novel therapies for the treatment of LG or Transformed LG NHL. New treatment options are necessary to provide greater clinical benefit evidenced by both response and duration of response."

In the News:

ASH Paper, 2013: A Randomized Phase II Study Comparing Consolidation With a Single Dose Of <sup>90</Sup>y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP.
Preliminary Results At 36 Months From Randomization

Patients with FL can have long time of survival, but disease progression typically occurs 3-5 years after initial treatment. Consolidation with Z after initial therapy has shown to improve progression-free survival (PFS) mainly in the pre-R era, whereas maintenance with R also has demonstrated a substantial benefit in terms of PFS in patients treated with immunochemotherapy.

In this setting, the Spanish intergroup PETHEMA/GELTAMO/GELCAB started a randomized phase 2 trial in order to compare the use of consolidation with Z vs. R maintenance in patients with FL responding to R-CHOP. From June 2008 to July 2010, 146 patients (66M/80F; median age, 55 years) were enrolled from 25 Spanish institutions in the randomized phase 2 trial ZAR2007

Main inclusion criteria were: FL grade 1, 2 or 3a, age 18-75 years, stages II-IV and need of treatment according to modified GELF criteria. Patients with FL grade 3b or transformed to DLBCL were excluded.

... The number of patients in PR after R-CHOP who reached CR during maintenance were 14 of 28 (50%) and 12 of 26 (46%) for arms A and B, respectively.

Two patients developed transformation to DLBCL at 8 (arm A) and 39 months (arm B) after randomization. During the maintenance period, patients receiving Z showed grade 3-4 neutropenia in 6 of 63 cases and grade 3-4 thrombocytopenia in 5 of 63, whereas these figures were 1 of 61 and 0 of 61 (p=0.05) for patients in arm B, respectively. No unexpected late toxicities have been reported.

Five patients have died during the follow-up due to the progression of lymphoma in all cases, with no differences between the arms (36-month OS, 98% vs. 95% for arms A and B, respectively). In conclusion, in patients with FL in response after R-CHOP, maintenance with R was superior to consolidation with Z in terms of PFS, with no differences in OS with the current follow-up.

Advocate comment:  That Rituxan competes with Zevalin for binding to cd20 could work against Zevalin in this study design - where induction included 4 cycles of Rituxan.  In the FIT study (leading to approval of Zevalin for this use) the induction therapy often did not include Rituxan. KarlS
Zevalin Consolidation of First Remission in Advanced-Stage Follicular Non-Hodgkin Lymphoma: Median Follow-Up of 7.3 Years From the International, Randomized, Phase III First-Line Indolent Trial”
Bexxar discontinued!
Radioimmunotherapy/Chemotherapy Combination Could Extend Survival in Some Patients with Advanced Lymphoma - The ASCO Post
Zevalin - Medscape: Renewed Interest in Ibritumomab for NHL



Reports on Outcomes

Radioimmunotherapy Consolidation in Mantle Cell Lymphoma PDF 

Wojciech Jurczak, European Oncological Disease - Published: October 2008
A thorough description of the rationale for consolidation with RIT for MCL – but also informative for other lymphomas.
Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma

Role of Different Frontline Regimens in Achieving Complete Response in Follicular Lymphoma: 
A Meta-Analysis of CR Rate and Its Relation to Hazard Rate for Disease Progression

Session Type: Poster Session, Board #932-II  ASH2006 

"Random effect estimation showed a CRR of 
   37% with CHEMO (95% CI: 18%57%), 
   53% with RCHEMO (34%71%), 
   68% with FLU (49%87%), and 
   79% with RIT (73%85%) 

"The analysis suggests that a higher CRR is correlated with a lower hazard of disease progression. 
These data support the selection of regimens that achieve high CRRs for future trials of initial therapy 
and could provide an additional basis for the design of long-term therapeutic strategies."

CHEMO - chemotherapy combinations without Fludarabine
R+/-CHEMO - rituximab as a single-agent or in combination with chemotherapy
FLU - fludarabine as a single-agent or in combination
RIT - Bexxar or Zevalin as  single agents or in combination


Bexxar as initial treatment for follicular lymphoma.
N Engl J Med. 2005 Feb 3;352(5):441-9. Abstract | Full Text

Seventy-six patients with stage III or IV follicular lymphoma ...After a median follow-up of 5.1 years, 
the actuarial 5-year progression-free survival for all patients was  59 percent, with a 
median progression-free survival of 6.1 years
. ...  Of 57 patients who had a complete 
response, 40 remained in remission for 4.3 to 7.7 years. Hematologic toxicity was moderate, with no 
patient requiring transfusions or hematopoietic growth factors. No cases of myelodysplastic syndrome 
have been observed.

bexxar-initial_tx.jpg (13092 bytes) click to enlarge chart showing progression free survival 

Update:  Bexxar® Provides Years of Lasting Activity as Initial Therapy 
in Follicular Lymphoma

* Overall survival at 10 years was 86%.  
* Anticancer responses were achieved in 95% of patients.
* A complete disappearance of detectable cancer (complete remission) 
   was achieved in 75% of patients.
* The median time for cancer progression among patients who achieved 
   a complete remission was 9.2 years.

Targeted Radio-Immunotherapy with Bexxar Produces Durable Remissions in Patients 
with Late Stage Low Grade Non-Hodgkin's Lymphomas.
Trans Am Clin Climatol Assoc. 2004;115:255-72. PMID: 17060972 

Response rates were 56% (overall) and 30% (complete). With a median follow-up of 44.6 months, 
30% of the patients achieved a long-term, durable response; median time to progressive disease 
or death was 5 years.


Bexxar radioimmunotherapy for relapsed or refractory B-cell non-Hodgkin lymphoma: 
updated results and long-term follow-up of the University of Michigan experience. 

Blood. 2000 Aug 15;96(4):1259-66. PMID: 10942366 | Related abstracts 

For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR
Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 
9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting.


Efficacy and safety of Bexxar in B-cell lymphoma, progressive after Rituxan. 
J Clin Oncol. 2005 Feb 1;23(4):712-9. Epub 2004 Dec 21. PMID: 15613695 

the OR and CR rates were 86% and 57%. Estimated 3-year Progression Free Survival  (PFS) in 
this subgroup was 48%, compared with 11% for all others (P = .002). 
Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary Myelodysplasia. 
CONCLUSION: (131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, 
with a 65% OR rate and median Progression Free Survival (PFS) of 24.5 months for responders
Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved  very high OR and 
CR rates, with 48% PFS at 3 years.


Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade 
non-Hodgkin's lymphoma.
Oncologist. 2004;9(2):160-72. Review. PMID: 15047920 

In clinical trials of Bexxar, objective response rates ranged from 54%-71% in heavily pretreated patients. 
In the pivotal trial, the number of patients with a longer duration of response after treatment with Bexxar 
was significantly greater than the number of patients with a longer duration of response after their 
last qualifying chemotherapy regimen. In 76 newly diagnosed patients, the objective response 
rate was 97%, and 63% of patients achieved complete responses. 


A clinical and scientific overview of tositumomab (Zevalin) and iodine I 131 tositumomab (Bexxar).
Semin Oncol. 2003 Apr;30(2 Suppl 4):22-30. Review. PMID: 12728404 

"these studies show that tositumomab and iodine I 131 tositumomab treatment is safe and 
induces high response rates and durable remissions in heavily pretreated patients with 
low-grade or transformed low-grade NHL"


Zevalin and Bexxar produces durable complete remissions in a subset of 
heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas.

J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. PMID: 16186600 

Response rates in the five trials ranged from 47% to 68%; CR rates ranged from 20% to 38%. 

With a median follow-up of 5.3 years, the 5-year progression-free survival was 17%. 
Eighty-one (32%) of 250 patients had a time to progression of > or = 1 year 
(termed durable response population).  For the durable response population, 44% had not progressed 
at > or = 2.5 to > or = 9.5 years and had a median duration of response of 45.8 months. 

The median duration of complete response was not reached. The durable response population had many 
poor prognostic characteristics, including bone marrow involvement (41%), bulky disease > or = 5 cm (49%),
and transformed histology (23%). Forty-three percent of the patients had been treated with more than four prior therapies and 36% had not responded to their most recent therapy.


Zevalin radioimmunotherapy produces high response rates and durable remissions 
in patients with previously treated B-cell lymphoma

Clin Lymphoma.
2004 Sep;5(2):98-101. PMID: 15453924 | Related abstracts 

In patients achieving a CR/CRu, the median TTP was 24.7 months for patients treated 
with 90Y ibritumomab tiuxetan compared with 13.2 months for rituximab-treated patients (P = 0.41), 
and ongoing responses of > 5 years have been observed.


Durable responses after ibritumomab tiuxetan radioimmunotherapy (Zevalin) for 
CD20+ B-cell lymphoma:  long-term follow-up of a phase 1/2 study.
Blood. 2004 Jun 15;103(12):4429-31.  Epub 2004 Mar 11. PMID: 15016644

"Nine patients (24% of responding patients) had a TTP of more than 3 years. 
Long-term responders (> 5 years) have been identified."


Leonard JP, Zelenetz AD, Vose JM, et al. Iodine I 131 tositumomab (Bexxar) for patients with 
low grade or transformed low grade NHL: complete response data. 
Blood. 2000;96(suppl 1):728a. Abstract 3148.

Summary data on 251 patients treated on various phase 1 to 3 tositumomab trials from 1990 to 1999.

Those characteristics statistically associated with a lower probability of achieving CR include 
bulky disease, prior chemotherapy, lack of response to last chemotherapy, and prior radiotherapy. 

Nonetheless, CR rates of 30% (confirmed) to 35% (not confirmed) may be expected in the group 
as a whole, with 3-year median duration of CR in those without confirmed CR and 
almost 5 years in those with confirmed CR status.

Radioimmunotherapy: FIT to be applied?  Randomized study shows improved PFS by 2 yrs in follicular lymphoma when given as consolidation for chemotherapy ( login req.)

n = The trial compared a single Zevalin treatment with observation in 414 patients with advanced (stage 3 or 4) follicular lymphoma who had achieved partial or complete remission after first-line chemotherapy. The choice of which chemotherapy regimen to use for induction was left to the physicians' discretion, and various combinations were used, including CVP, CHP, fludarabine, chlorambucil, and rituximab.
See also: Bulky disease and RIT?


Contraindications for use of RIT

Some of these "cutoffs" may have changed since the post date


Bone marrow biopsy results:


Hypocellular bone marrow (<15% cellularity)


Marked reduction of bone marrow precursors
NOTE:  The bone marrow findings must be within 30 days


Impaired bone marrow reserves as indicted by:


prior myeloablative therapies with ABM or PBSC transplantation


Platelet count < 100,000 cells/mm3  (or perhaps < 50,000 for Zevalin)


ANC (Neutrophil Count (Absolute)) < 1,500 cells/mm3


History of failed stem cell collection


Known type I hypersensitivity or anaphylactic reactions to murine (mouse) proteins (HAMA)
or to any component of the therapeutic regimen


Positive pregnancy test - test required for women of child-bearing age.


Serum Creatinine > 1.5 X the upper limit of normal


Previous external beam radiation involving >25% of the active bone marrow


Pregnancy and continuing breast feeding


Children and adolescents under 18 years of age


Prior bone marrow or stem cell transplantation (this is being studied)

Adapted from:  |  pdf  

FDA Label describing use for


RIT for the Elderly?

Bexxar is an Effective and Well Tolerated Therapy in Elderly Patients with NHL

CONCLUSION: Bexxar was efficacious and well tolerated in this population of elderly patients with NHL. Due to physiologic changes in the elderly, conventional chemotherapy may require dose-attenuation; however, Bexxar therapy provides pt-optimized dosing so that the same TBD is given for all age groups. This novel therapy provides a therapeutic choice for pts who may have limited therapeutic options.

When to Consider RIT? ... Patient Perspectives

When might RIT be appropriate ... indicated ... deserving of full consideration?

FDA approved indications for RIT: "for the treatment of relapsed or refractory low grade, 
follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL)."   

Also see our brochure on this topic: RIT.pdf

Treatment decisions are complex. See Factors that Influence Treatment Decisions

Important: Treatment decisions are complex and require input from well-trained, experienced lymphoma specialists. All therapies have risks and outcomes will vary. Please discuss the risks and benefits of all reasonable therapies when consulting your physician. Items below marked with * indicate investigational uses. See Locating RIT-Based Clinical Trials

As first primary treatment, perhaps as an alternative to chemotherapy, particularly if chemotherapy is not indicated for you. *
As consolidation therapy? *
Consolidation therapy is a treatment given shortly after another treatment with the goal of improving on the response. (Also called sequential therapy.)
As second primary treatment, particularly following a short or insufficient response to prior treatment? 

A primary treatment is one that is given with intent to achieve a significant and long lasting response, as opposed to palliative therapy where the goal might be to relieve symptoms.
When you have relapsed from prior treatment, and the goal of your next therapy is to achieve a durable complete remission.
As an alternative to stem cell transplantation (SCT), particularly if SCT is indicated, but not suitable for you because of age or other factors. *
As part of the conditioning therapy of stem cell transplantation? *
As an alternative to maintenance Rituxan
Maintenance is the regularly scheduled administration of Rituxan with the goal of maintaining the response to prior induction treatment.
When transformation is suspected and you are not a candidate for SCT, or combination chemotherapy, such as CHOP-Rituxan? 
Transformation is a change in the indolent lymphoma cells that leads to more aggressive clinical behavior and/or resistance to standard treatment.

NOTE: Clearly, the selection of treatment should be based on individual clinical details, and a realistic assessment of the most appropriate treatment goal.  We have a concern that for non-clinical reasons*  RIT is not being considered in some clinical centers.  


See Locating RIT-Based Clinical Trials


Non-clinical factors that may influence underutilization of RIT

Lack of awareness of the potential of RIT to result in higher remission 
rates and duration of remission among patients and some oncologists.
When insurance carriers do not cover treatment out of network/area, 
and the patient's treating physician does not offer nuclear medicine.
A conflict of interest (mostly unintended) that occurs when physicians cannot 
offer the full range of therapies within their local practice.
When the potential risks of RIT are overestimated or not fully understood 
by patients and physicians.

What is the most appropriate goal of treatment for RIT?

Our impression is that RIT is best used when the goal of treatment is to potentially 
cure or obtain a durable complete remission ... and that may not be as appropriate as 
management therapy, because it cannot be given at  frequent intervals to control the disease. 

Therefore, if you have bulky disease, you may want to consider de-bulking prior to use of RIT, 
as lower tumor burden is associated with better and more durable outcomes (O. Press). 
However, use of chemotherapy shortly before RIT could also increase risks of RIT

Pretreatment might also include stem cell harvesting. 
Pretreatment (sequential therapy) can also improve the safety of RIT by 
decreasing the % of bone marrow involvement as described here:

Radioimmunotherapy in the treatment of low grade b-cell lymphoma PDF 
Please consider the above as ideas and factors that may guide the discussions with your 
doctor and the outside experts you may consult. It should not be regarded as medical advice.    


Questions and Comments for Experts

Comparing Sequential chemo-RIT with autologous SCT?  We believe a study comparing the following protocols would answer an important clinical question, and would also be of interest to patients with high-risk lymphomas referred to a transplantation center:  

Sequential HD chemo - (with harvesting), sequenced with RIT versus Autologous SCT  

Importantly, harvesting of stem cells in the Sequential therapy arm of the study will facilitate subsequent use of SCT should be needed. 

Data on Long-term outcomes: There's a need to conduct a meta-analysis that describes the potential long term benefits and risks of RIT across many studies.  It appears that lacking this information, clinical decisions are defaulting to what is less toxic in the short term and offered at the patient's local center.  

High Dose RIT as an alternative to SCT? When is high dose (HD) radioimmunotherapy indicated? Can HD radiotherapy be used outside a clinical trial in cases where it is indicated?  Lay comment: One indication for HD RIT seems to be in preparation for stem cell transplants, especially when conditioning chemotherapy fails to achieve a remission.

Extranodal disease and RIT: Does mucosal (gastric MALT) or CNS involvement preclude the use of radioimmunotherapy? 


Does spleen involvement preclude use of radioimmunotherapy?

Splenectomy in Non-Hodgkin's lymphoma

Residual splenomegaly in a patient who has otherwise successfully responded in other sites following chemotherapy for lymphoma is another reason for performing a splenectomy. In these cases, the procedure may be performed for both diagnostic and therapeutic reasons; it can determine if the splenomegaly is due to persistent lymphoma, and should this be true, it can potentially eliminate the focus of residual disease. A less common indication for splenectomy that may be seen more frequently in the future is to allow patients to become eligible for enrollment onto novel treatment protocols. An example of this is in patients with lymphoma refractory to conventional chemotherapy who were treated with radioimmunotherapy using a radiolabelled anti-CD20 antibody.

In some of these patients, splenomegaly was found to complicate treatment, as the large organ served as an “antigen sink”, effectively decreasing the dose of radionuclide available to treat other sites of disease. Thus, pretreatment splenectomy may be indicated to eliminate this complicating factor.

Radioimmunotherapy for other types of lymphoma?

Disclaimer:  The information on is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns, you should always consult your doctor. 
Copyright © 2004,  All Rights Reserved.