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Treatment Overview >  Zevalin

Last update: 09/28/2016

RELATED  ADVOCACY TOPICS

Our letter to the ASCO Post:
Limited Access to Radioimmunotherapy in Community Setting
May Lead to Extinction of a Unique Lymphoma Treatment http://bit.ly/2cOp48Z 

Our Letter educating our elected representatives on the impact of an NRC decision
on the availability of radioimmunotherapy in the community setting: 

Further below
we provide a list of Senators who have oversight over the NRC
Senators on oversight committee

You may also communicate with
Your State Senator with our zip code tool

Zevalin - a snapshot of its unique properties

Catch 22:

 

See also our more recent
   letter to Vice President Joe Biden

Senators with oversight over the Nuclear Regulatory Commission

Senate HELP (Health, Education, Labor, and Pensions) Committee
http://www.help.senate.gov/about/members  


The Honorable Senator Lamar Alexander
Chairman, HELP Committee
455 Dirksen Office Building,
Washington, DC 20510

Phone: (202) 224-4944
Fax: (202) 228-3398


The Honorable Senator Patty Murray
Ranking Member, HELP Committee
154 Russell Senate Office Building
Washington, D.C. 20510
Phone: (202) 224-2621
Fax: (202) 224-0238
Toll Free: (866) 481-9186

The Honorable Senator Michael B. Enzi
HELP Committee
379A Senate Russell Office Building
Washington, DC 20510
Phone: (202) 224-3424

Fax: (202) 228-0359
Toll-Free: (888) 250-1879


The Honorable Senator Richard Burr
HELP Committee
217 Russell Senate Office Building
Washington, DC 20510
P: (202) 224-3154
F: (202) 228-2981+

The Honorable Senator Johnny Isakson
HELP Committee
131 Russell Senate Office Building
Washington, DC 20510

Tel: (202) 224-3643
Fax:
(202) 228-0724


The Honorable Senator Rand Paul
HELP Committee
167 Russell Senate Office Building
Washington DC, 20510
Phone: 202-224-4343


The Honorable Senator Susan Collins
HELP Committee
68 Sewall Street, Room 507
Augusta, ME 04330 
Main: (207) 622-8414

The Honorable Senator Lisa Murkowski
HELP Committee
709 Hart Senate Building
Washington, D.C. 20510

Main: 202-224-6665
Fax: 202-224-5301

The Honorable Senator Mark Kirk
HELP Committee
524 Hart Senate Office Building
Washington DC, 20510
Phone: 202-224-2854
Fax: 202-228-4611

The Honorable Senator Tim Scott
HELP Committee
520 Hart Senate Office Building
Washington, DC 20510
Phone: (202) 224-6121, Toll Free: (855) 425-6324
Fax: (202) 228-5143


The Honorable Senator Orrin Hatch
HELP Committee
104 Hart Senate Building
Washington, D.C. 20510
Main: 202-224-5251
Fax: 202-224-6331

The Honorable Senator Pat Roberts
HELP Committee
109 Hart Senate Office Building
Washington, DC 20510-1605
Phone: 202-224-4774
Fax: 202-224-3514

The Honorable Senator Bill Cassidy, M.D.
HELP Committee
703 Hart SOB
Washington, DC 20510

Phone: (202) 224-5824
Fax: (202) 224-9735

The Honorable Senator Barbara Mikulski
HELP Committee
503 Hart Senate Office Building
Washington, D.C., 20510

PHONE: (202) 224-4654

The Honorable Senator Bernie Sanders
HELP Committee
332 Dirksen Building
Washington, D.C. 20510

tel (202) 224-5141
fax (202) 228-0776


The Honorable Senator Robert P. Casey, Jr
HELP Committee
393 Russell Senate Office Building
Washington, D.C. 20510

Phone: (202) 224-6324
Toll Free: (866) 802-2833
Fax: (202) 228-0604


The Honorable Senator Al Franken
HELP Committee
60 East Plato Blvd
Suite 220
Saint Paul, MN 55107
(651) 221-1016

 

The Honorable Senator Michael F. Bennet
HELP Committee
261 Russell Senate Office Building
Washington, DC 20510

hone: 202-224-5852
Fax: 202-228-5097 


The Honorable Senator Sheldon Whitehouse
HELP Committee
Hart Senate Office Bldg. Room 530
Washington, DC, 20510

P: (202) 224-2921
F: (202) 228-6362


The Honorable Senator Tammy Baldwin
HELP Committee
717 Hart Senate Office Building
Washington, D.C. 20510
Phone: (202) 224-5653

The Honorable Senator Christopher S. Murphy
HELP Committee
136 Hart Senate Office Bldg.
Washington, DC 20510

P: (202) 224-4041
F: (202) 224-9750

The Honorable Senator Elizabeth Warren
HELP Committee
317 Hart Senate Office Building
Washington, DC 20510
Phone: (202) 224-4543

 


Zevalin radioimmunotherapy (RIT) - snapshot of its unique properties

  - 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.

See also the
unique mechanistic properties of RIT --as a strong rationale for continued testing

- It's proven potential to induce durable remissions with a very short course of therapy,
 allowing for the study of consolidation immunotherapies given after recovery of immune function.

- It is an antibody-based therapy and therefore less likely to have adverse interactions with other drugs
given before, during, and after RIT
- It is targeted to cd20, focused on b-cells, and therefore will have less impact on other effector cells
needed to mediate an immune response

RIT is not typically offered to patients as a choice

  - in part because most oncologists are not authorized to administer it
    700 hours of training is required by the NRC (See our letter to the NRC protesting the increase in training time PDF)

  - the oncologist must send their patients somewhere else to be treated*
    
* Follicular Lymphomas, Dr. Bruce Cheson, LRF Education Forum http://bit.ly/1QEfIft (advance to slide 61)

 
- low awareness among non-certified community oncologists about the unique properties of RIT and how this may influence patient preferences.

More about Zevalin | How is Zevalin Given?  Resources | News and Abstracts

We are not physicians. 
We are not advocating that oncologists recommend RIT as THE preferred treatment.

bullet
We urge consideration by patients of the following study:

Testing Rituximab With or Without Zevalin in patients with
Untreated Follicular Lymphoma without a current need to treat http://1.usa.gov/1xhtOvA
bullet
We urge oncologists to become more familiar with the indications for radioimmunotherapy
and the unique properties of RIT described above, so you can provide the information
your patients need to make an informed choice.
bullet
We urge the Nuclear Regulatory Commission to return to the 80 hour training requirement
so that more oncologists can be authorized to administer RIT in the community setting
again, when it's indicated and when it's the patient's preferred choiceOur letter to NRC: PDF

Access to RIT in the community setting is a vital if we are to honor the Belmont principle of Justice*
We remind that many insurance policies do not support receiving therapies out of network; and that travel to nuclear medical facilities will not be feasible for many patients due to their age, secondary medical conditions, frailty, and their income status.


Belmont report: “Justice requires that individuals and groups be treated fairly and equitably in terms of bearing the burdens and receiving the benefits of research.”

bullet
And we urge clinical investigators and drug sponsors to rigorously study RIT, such as in combination with targeted drugs or in sequence with immunotherapy. The mechanistic properties of RIT provide the rationale: 

- It's proven potential to induce durable remissions with a very short course of therapy,
 allowing for the study of consolidation immunotherapies given after recovery of immune function.

- It is an antibody-based therapy and therefore less likely to have adverse interactions with other drugs
given before, with, and after RIT
- It is targeted to cd20, focused on b-cells, and therefore will have less impact on other effector cells
needed to mediate an immune response
Efficacy of RIT - Related citations
bullet 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
 
bullet Kaminski, 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 
 
bullet Radioimmunotherapy of B-Cell Non-Hodgkin’s Lymphoma http://1.usa.gov/1LbrnSC

"Despite the lack of phase III studies to clearly define the role of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in B lymphoma has been demonstrated, with the likelihood of providing a durable response." 
 
bullet Indications:
Zevalin is an FDA-approved treatment for
relapsed refractory indolent lymphoma, and for
previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy

(full prescribing information)
 

Clinical considerations and risks of RIT  - an overview

There is no avoiding risk. When we make a decision we trade one kind of risk for another. Virtually all approaches to managing lymphoma will have risks, including observation.   Chemotherapy-based protocols also have risks, some of these are similar to RIT. What follows are some generally accepted principles that can help patients to make an informed choice in consultation with their physicians.

Risk/benefit assessments: We can think of induction therapies as approaches to treatment having greater possible risks but also having greater potential reward. The intent or goal of induction therapy is to achieve a more durable remission and possible cure. Using this definition, both RIT and Rituxan-based chemotherapy are induction approaches - having different types of risks, durations on treatment, and side effects.

Management
or palliative approaches are those that give minimal treatment (usually single agents) sufficient to reduce the symptoms of the disease, but not generally sufficient to induce a durable remission.  Maintenance schedules of such agents, commonly Rituxan, are sometimes used over many months or years. 

Apples to Oranges: it's challenging to compare the possible risks and potential benefits of RIT with chemotherapy approaches.  The same holds for comparing Rituxan (a management approach) to RIT (an induction therapy). An induction treatment having more possible side effects or more significant but uncommon serious risks, may have less risk overall when or if it achieves a durable remission ... compared to management with a drug with lower toxicity given repeatedly over many years.

Treatment history: The best opportunity to achieve a durable remission from standard treatments is with initial therapy and first or second relapse. 

Tumor burden and areas of presentation:  The size of tumor can influence the potential for a durable response to treatment.  For example, de-bulking treatment followed by consolidation with RIT might be considered if one or more tumors are very large. See also Bulky disease and RIT?  

Having high levels of lymphoma in the bone marrow or spleen can increase the risk of RIT because it emits radiation to bystander cells.  See also: Relationship of degree of bone marrow involvement with hematologic toxicity in patients with non-Hodgkin's lymphoma treated with tositumomab and iodine I 131 tositumomab.  ASCO 2003 

Treatment-related MDS/AML (secondary cancers, which does not appear to be a greater for RIT than for chemotherapy) in patients with follicular lymphoma after frontline therapy with tositumomab and iodine I 131 tositumomab  ASCO 2003 

"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 http://bit.ly/7mcys1


Safety overview: The iodine I-131 tositumomab therapeutic regimen: Summary of safety in 995 patients with relapsed/refractory low grade (LG) and transformed LG non-Hodgkin's lymphoma (NHL)  jco.org 

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

Competing choices:  

Recognition is needed that many patients when sufficiently informed about the unique properties of RIT may have a preference for RIT treatment over the competing choices.  Being fully informed about all of our choices is not easy ... but should be standard practice.  We urge the NCCN to develop patient materials for this purpose.

Because of the dwindling usage of RIT, it's important to underline and communicate broadly about its unique positive properties:  that RIT is the only potent (non-palliative), and tolerable induction therapy available to the elderly and frail.  Fostering community access to RIT (by NRC policy decisions) is important because a good many people with lymphoma may be unable to travel to a nuclear medicine center due to their physical limitations.  Further, people with limited income will not be able to afford the travel, or to take time off from work.  Health insurance policies often restrict out-of-network use.

As Einstein noted: "Not everything that counts can be counted."   Clearly, an 8-fold increase in training will be a barrier to oncologists who might otherwise consider becoming authorized users of radioimmunotherapy.  Oncologists who are not authorized to give RIT have an inherent conflict of interest -- it is a disincentive to inform patients about an approach to treating indolent lymphoma that they cannot administer.  This is a major concern as it has been reported that 85% of cancer patients are treated in community setting - Cohen. Cancer J Clin 2003;53:73-81

Our duty is to find ways to maintain and improve awareness of this approach and to maintain and increase access in the community setting.   These important goals require policies that make it feasible for oncologists to receive the training needed to administer it. 

Clinical trial results and its unique properties support the continued use and additional study of FDA-approved RIT.  The durable outcomes that can be achieved with RIT (equivalent to chemotherapy) are rarely achieved with palliative measures (Rituxan, doublets, etc.). 

Perceptions and Evidence
-- we still do not know how RIT compares to standard R-chemo for indolent lymphoma

The outcomes were compelling in the Kaminski study of Bexxar for untreated follicular lymphoma.  But the findings could not change practice because of the single-arm study design.  NEJM, Kaminski, full text

To date, we have not had a completed study comparing R-chemotherapy to RIT monotherapy, or RIT to Rituxan monotherapy. The lack of a definitive study on the superiority of RIT monotherapy likely contributes to the apparent incorrect perception among many oncologists that routinely informing patients about the unique properties of RIT is not required.  Clinical impressions on the value of RIT in the relapse setting could well be from turning to this approach too late, when all approaches available to the community oncologist have been exhausted.

Since not all patients with lymphoma can tolerate chemotherapy, it's vital that we utilize RIT fully when it's appropriate and/or preferred by the informed patient.  The unique mechanistic properties of RIT provide a strong rationale for testing RIT give with targeted drugs and with other immunotherapies.

Related articles

bullet
Zevalin - indications, FDA-full prescribing information PDF: http://bit.ly/1QABcbG 

Zevalin is a CD20-directed radiotherapeutic antibody administered as part of
the Zevalin therapeutic regimen indicated for the treatment of patients with:
• relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) (1.1).
• previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy (1.2).
bullet
8-fold increase in required training (from 80 hours to 700) needed to authorize
the administration of Zevalin is a barrier to patient access. Print version - PDF
bullet
Looking back, 2006: Follicular Lymphomas, Dr. Bruce Cheson, LRF Education Forum
Zevalin discussion starts on slide 61.  http://bit.ly/1QEfIft  

Most effective, least used treatment in oncology. Easily tolerated, and yet you can't sell it.
... reasons, many (one is it requires the oncologist to send the patient someplace else to get treated" 
bullet
Radioimmunotherapy of B-Cell Non-Hodgkin’s Lymphoma http://1.usa.gov/1LbrnSC
(Improved Awareness of the RIT option is needed)

TOPIC SEARCH PubMed:      
Outcomes | Safety
 

 

 

Introduction - About Zevalin:

Zevalin (Ibritumomab tiuxetan) is a radio-labeled antibody.  The antibody seeks and binds to cells that have a receptor called CD20 -- present on both normal and malignant mature b-cells. 

Once bound to the target cells, Zevalin delivers radiation, which enhances the killing effect of the antibody.  

Because immature b-cells do not have the CD20 receptor, normal b-cells will recover in about nine months after treatment.

Rituxan (the naked antibody) is administered prior to Zevalin with the goal of clearing the majority of normal b-cells so that the therapeutic dose (the radio-labeled antibody) is more focused on tumor cells. 

Research Findings and News

bullet
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” http://bit.ly/1khWdEV
 
bullet
Br J Haematol 2013:
Safety and efficacy of Zevalin for untreated follicular lymphoma patients. An Italian cooperative study.  http://1.usa.gov/1a1HKJ9

Single arm study:  50 patients with stage II "bulky", III or IV FL received a single treatment course with (90 Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated LDH level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively.
bullet
Zevalin - Medscape: Renewed Interest in Ibritumomab for NHL
bullet
Zevalin, Fludarabine, and TBI-based "mini" allogeneic transplantation
bullet
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 http://bit.ly/17jNgpg

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 for this use) the induction therapy often did not include Rituxan. KarlS

 

Who is Zevalin for?

Patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with Rituximab refractory follicular non-Hodgkin's lymphoma. Update: Zevalin is also indicated for the treatment of previously untreated follicular NHL in patients who achieve a partial or completed response to first-line chemotherapy.  

Repeated Use of ZEVALIN? The entire ZEVALIN therapeutic regimen is intended as a one-time treatment. The safety profile from multiple courses of the ZEVALIN therapeutic regimen or other forms of therapeutic radiation preceding, following, or in combination with the ZEVALIN therapeutic regimen has not been established.

The effects of Zevalin on survival is unknown.  

Mechanism of Action

After Y-90 ZEVALIN (the therapeutic component of the ZEVALIN regimen) enters the bloodstream, the monoclonal antibody ibritumomab recognizes and attaches to the CD20 antigen, allowing beta radiation emitted by the Yttrium-90 isotope to penetrate and damage the B-cell as well as neighboring cells.

Treatment with ZEVALIN: The entire ZEVALIN therapeutic regimen is delivered over 7 to 9 days. Patients then receive follow-up care by a physician for at least an additional 12 weeks. The ZEVALIN therapeutic regimen can be administered entirely on an outpatient basis and no isolation or lead shielding is necessary.

Where can I receive treatment?
You can use the Treatment Site Locator 


How Zevalin Is Given? 

Note: The Bioscan step is no longer required with Zevalin therapy

Zevalin is a two step protocol administered by IV over 7 to 9 days. 

Step 1, Day 1:  Rituxan infusion of 250 mg/m2 - starting at a slow rate.  

Step 2 Seven to nine days later:
 
Rituxan infusion is given a second time as described above. 

Within 4 hours the treatment dose of Zevalin (Zevalin linked with Yttrium-90) 
is infused over 10 minutes. 

The dose of Zevalin given depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated. 

Ongoing Studies Clinical studies at major medical centers are currently investigating the use of the ZEVALIN therapeutic regimen in a variety of other lymphoma subtypes including aggressive disease. The ZEVALIN therapeutic regimen is also being studies in a number of different treatment strategies including combinations with front-line and salvage chemotherapy regimens and as part of autologous and allogeneic stem cell transplantation.

Contraindicated (not for): Patients with known Type I hypersensitivity or anaphylactic reactions to murine (mouse)  proteins or to any component of this product, including Rituxan, yttrium chloride, and indium chloride. Zevalin should not be administered to patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve.

Median time to nadir (low blood counts): "Median time to ANC nadir was 62 days, to platelet nadir was 53 days, and to hemoglobin nadir was 68 days"
 
 Source:
Zevalin

gr_zevalin.gif (14229 bytes)
Click to enlarge

 


Resources:

bullet
Zevalin Company Support, reimbursement and availability questions:

By Web: zevalin.com/

By Phone: 1-866-298-8433

   Option 1: Customer Service / Orders

   Option 2: Medical Information or Adverse Events Reporting

   Option 3: Product Complaints

   Option 4: Reimbursement

   Option 5: Rituximab Questions

By Email: ZEVALINsupport@sppirx.com

 
bullet
Full prescribing information Zevalin.com
 

Does spleen involvement preclude use of radioimmunotherapy?

Splenectomy in Non-Hodgkin's lymphoma  ncbi.nlm.nih.gov/books

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.

 


Related Topics

bullet
Antibodies for NHL

News and Abstracts

 

ASH 2010: Zevalin-based abstracts

90Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin’s Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

http://ash.confex.com/ash/2010/webpr...aper28386.html

SNIPS:

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%).

Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008;

Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR).

Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561).

To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group.

Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063).


Other Zevalin reports at ASH 2010:

A Multi-Center Prospective Randomized Study Comparing Ibritumomab Tiuxetan (Zevalin) and High-Dose BEAM Chemotherapy (Z-BEAM) Vs. BEAM Alone as the Conditioning Regimen Prior to Autologous Stem-Cell Transplantation In Patients with Aggressive Lymphoma; Possible Advantage for Z-BEAM In Low-Risk Patients
http://ash.confex.com/ash/2010/webpr...aper28200.html

Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan (Zevalin) In Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL): Final Analysis
http://ash.confex.com/ash/2010/webpr...aper27049.html

The Risk of Secondary Myelodysplastic Syndrome/Acute Leukemia Following High-Dose Yttrium-90 Ibritumomab Tiuxetan Is Analogous to That Observed Following High-Dose Chemotherapy: a Matched-Pair Analysis In Non-Hodgkin Lymphoma Patients
http://ash.confex.com/ash/2010/webpr...aper30605.html

Update on a Prospective Study Evaluating the Safety and Efficacy of Combination Therapy with Fludarabine, Mitoxantrone and Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan and Maintenance Rituximab as Front Line Therapy for Patients with Indolent Lymphomas
http://ash.confex.com/ash/2010/webpr...aper26924.html

90Yttrium Ibritumomab Tiuxetan as First Line Treatment for Follicular Lymphoma. First Results from an International Phase II Clinical Trial
http://ash.confex.com/ash/2010/webpr...aper33702.html

Bortezomib May Be Safely Combined with Y-90 Ibritumomab Tiuxetan In Patients with Relapsed/Refractory Follicular or Transformed Non-Hodgkin Lymphoma: A Phase I Trial of Combined Induction Therapy and Bortezomib Consolidation
http://ash.confex.com/ash/2010/webpr...aper28666.html

Comparative Analysis of Autologous Hematopoietic Cell Transplantation with Radioimmunotherapy (RIT) Based Conditioning Versus Total Body Irradiation (TBI) for High-Risk Diffuse Large Cell Lymphoma (DLCL): Toxicity and Efficacy
http://ash.confex.com/ash/2010/webpr...aper29132.html


90Υ-Ibritumomab Tiuxetan Followed by Rituximab Is a Safe Treatment Option for Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin s Lymphoma
http://ash.confex.com/ash/2010/webpr...aper31933.html

 

 

 

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Zevalin as a Single Agent in Patients With Pretreated B-Cell Lymphoma: Evaluation of the Long-Term Outcome  http://bit.ly/doQm0a 

Overall response rate was 93% (53 of 57); complete response (CR) rate was 70% (40 of 57). Twenty-six of 40 patients (65%) who obtained a CR are in continuous CR (CCR) with a median follow-up of 20 months (range, 10-42 months); 4 of them still maintain their CCR after 36 months.
 
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NEW Radioimmunotherapy: FIT to be applied?  Randomized study shows improved PFS by 2 yrs in follicular lymphoma when given as consolidation for chemotherapy  Medscape.com ( 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.
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Zevalin Licensed For First Line Consolidation Therapy for fNH, May 2008 medicalnewstoday.com

"It is particularly impressive that with one single infusion of Zevalin, we have achieved prolongation of median progression free survival by two years, with a favorable toxicity profile," said Professor Anton Hagenbeek, Academic Medical Centre, Amsterdam, the Netherlands, lead investigator of the FIT trial.
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 Zevalin in Mantle Cell Lymphoma touchbriefings.com   pdf  2007

Conclusion: Radiotherapy is an active treatment modality in MCL. Ibritumomab radioimmunotherapy (Zevalin) is an interesting alternative to other consolidation methods. In younger patients subjected to intensive chemotherapy followed by autologous transplant, it may be an element of a transplant conditioning regimen (i.e. Z-BEAM). In elderly patients, the role of zevalin consolidation should be further investigated in a phase III trial.
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Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials. J Nucl Med. 2003 Mar;44(3):465-74. PMID: 12621016 

Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.
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Salvage therapy for primary Central Nervous System lymphoma with (90)Y-Ibritumomab and Temozolomide. J Neurooncol. 2007 Jul;83(3):291-3. Epub 2007 Jan 24. PMID: 17245621 

Aggressive initial treatment of Primary Central Nervous System Lymphoma (PCNSL) has achieved prolonged survival and occasional cures. However, some patients do not respond to initial therapy and others relapse after an initial remission. The optimal salvage regimen is not known and many different strategies have been proposed. In this report we describe the efficacy of a combination of (90)Y-Ibritumomab Tiuxetan (Zevalin) and Temozolamide as a maintenance therapy for recurrent PCNS Lymphoma in two patients that are both alive and in complete remission after 9 and 10 months respectively. This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL.
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Zevalin: Risk of MDS/AML update  www.fda.gov | Zevalin_PI.pdf 

"Myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML) were reported in 5.2% (11/211) of patients enrolled in clinical studies and 1.5% (8/535) of patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to the diagnosis of MDS or AML was 1.9 years following treatment with the Zevalin therapeutic regimen; however, the cumulative incidence continues to increase."
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Analysis of the Incidence of Treatment-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Registration and Compassionate-Use Trials of Ibritumomab Tiuxetan Radioimmunotherapy (RIT). Session Type: Oral Session  ASH 2006
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Zevalin update:  Biogen Idec and FDA notified healthcare professionals of revision to BOXED WARNINGS, WARNINGS, and ADVERSE REACTIONS sections of the Prescribing Information to describe severe cutaneous (skin) or mucocutaneous (mucosal linings) reactions, some with fatal outcome, that have been reported in association with the Zevalin therapeutic regimen in the post-marketing experience.   fda.gov/medwatch | medpagetoday.com 
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Follow-up results of a phase II study of ibritumomab tiuxetan radioimmunotherapy in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma and mild thrombocytopenia. Cancer Biother Radiopharm. 2004 Aug;19(4):478-81. PMID: 15453962
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ASCO 2003 - Report on Zevalin - durable responses; safety as second- or third-line therapy  Buswire
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4-year data: Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin's Lymphoma. J Clin Oncol. 2003 Apr 1;21(7):1263-70. PMID: 12663713  PubMed
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Durable Remissions Obtained with Zevalin in Recurrent Follicular Lymphoma  CancerConsultants.com 
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Zevalin: Full Prescribing Information  IDEC
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Subsequent Therapy Well Tolerated in Patients Previously Treated with Zevalin (tm)   411cancer.com  
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Zevalin Reimbursement Support  IDEC
Information on how to navigate through the complex maze of health insurance requirements
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Zevalin Safe For Patients Who Have Had Prior Radiation  OncoLink  10-9-02 2002  (scroll down after reaching page)
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Subsequent Therapy Well Tolerated in Patients Previously Treated with Zevalin (tm)  www.vacancer.com
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Biologic License Application PDF | PDF-Help
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90Y ibritumomab (Zevalin) in aggressive non-Hodgkin's lymphoma: analysis of response and toxicity Year: 2002 Abstract No: 1061
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90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy does not preclude effective delivery of subsequent therapy for lymphoma Year: 2002 Abstract No: 1064
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90Y-ibritumomab tiuxetan (Zevalin) radioimmunotherapy for transformed B-cell non-HodgkinÝs lymphoma (NHL) patients Year: 2002 Abstract No: 51
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Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or  transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. PMID: 12011122   PubMed
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Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood. 2002 Jun 15;99(12):4336-4342. PMID: 12036859  PubMed  (Lower dose used.)
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RIT and risk of MDS: Treatment-related myelodysplastic syndrome (MDS) and AML in patients treated with Zevalin radioimmunotherapy. J Clin Oncol. 2007 Sep 20;25(27):4285-92. Epub 2007 Aug 20.
PMID: 17709799 

Analysis of data from patients ... (746 patients) ... incidences of t-MDS and t-AML (0.7% per year after treatment) are consistent with that expected in patients with NHL who have had extensive previous chemotherapy treatment and do not appear to be increased after treatment with the ibritumomab tiuxetan regimen.
 
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