MEDICAL POLICY

POLICY
RELATED POLICIES
POLICY GUIDELINES
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Monoclonal Antibodies for the Treatment of B-Cell Malignancies

Number 2.03.502

Effective Date October 14, 2013

Revision Date(s) 10/14/13; 09/11/12; 07/12/11; 08/10/10; 05/12/09; 06/10/08; 04/10/07; 12/12/06;10/11/05; 12/14/04

Replaces 2.03.05

Policy

Rituxan®

Rituximab (Rituxan®) is a CD-20 directed cytolytic antibody and may be considered medically necessary (for the following labeled indications)in the treatment of patients with:

  • Non-Hodgkin’s Lymphoma (NHL), and
  • Chronic Lymphocytic Leukemia (CLL).

Rituximab (Rituxan®) may be considered medically necessary for the following off-label indications:

  • Treatment of any B-cell or other Lymphoid malignancies that express CD-20 antigen, including but not limited to, ALL, CLL/SLL, primary CNS lymphomas, AIDS-related B-cell lymphoma, follicular lymphoma, hairy cell leukemia, lymphoblastic lymphoma, MALT lymphoma, Hodgkin’s lymphoma, Burkitt’s lymphoma, mantle cell lymphoma, splenic marginal zone lymphoma, multiple myeloma and Waldenstrom’s macroglobulinemia and CD-20 positive leptomenigeal metastases.
  • Treatment of posttransplant lymphoproliferative disorder:
  • First-line therapy of monomorphic or polymorphic PTLD
  • Second-line therapy for persistent or progressive PTLD
  • Maintenance therapy for polymorphic PTLD

Rituximab (Rituxan®) is considered investigational for the following off-label indication:

  • Treatment of lymphoid B-cell malignancies that do not express CD20- antigen.

Arzerra®

Ofatumumab (Arzerra®) may be considered medically necessary for the following labeled indication:

  • Treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

Ofatumumab (Arzerra®) may be considered medically necessary for the following off-label indication:

  • Salvage treatment of Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic lymphoma in rituximab-intolerant patients.

Related Policies

5.01.526

Pharmacotherapy of Idiopathic Thrombocytopenic Purpura (ITP) in Adults

5.01.549

Off-Label Use of Drugs and Biologic Agents

5.01.601

Pharmacologic Treatment of Rheumatoid Arthritis, Other Arthropathies and Miscellaneous Autoimmune Diseases

8.01.50

Radioimmunotherapy in the Treatment of Non-Hodgkin Lymphoma

Policy Guidelines

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is classified as an indolent non-Hodgkin’s lymphoma (NHL). When CLL/SLL is relapsed or refractory and CD20+ B-cells (not T-cells) are present, treatment is appropriate with Rituximab.

Rituxan and Arzerra are intended for IV infusion administration.

Description

Normal and malignant hematopoietic cells express various antigens on their surfaces, including: CD20 expressed by B-lymphocytes and B-cell malignancies; CD33, present on myeloid progenitors and acute myeloid leukemia (AML); and CD52, expressed by normal and malignant T- and B-lymphocytes. Monoclonal antibodies have been developed to each of the above antigens and have been investigated for the following labeled and off-label uses.

Rituximab (Rituxan®) is a CD-20 directed cytolytic antibody indicated for the treatment of patients with following labeled indications:

  • Non-Hodgkin’s Lymphoma (NHL), and
  • Chronic Lymphoctyic leukemia (CLL).

Ofatumumab (Arzerra®): human monoclonal antibody to the CD20 antigen.

Labeled indications:

  • Treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

NCCN Compendium

The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium is based directly on the NCCN Clinical Practice Guidelines in Oncology. The compendium lists specific panel recommendations for off-label uses of drugs, and each recommendation is supported by a level of evidence category.

The NCCN Categories of Evidence and Consensus used in the recommendations are:

  • Category 1: The recommendation is based on high level evidence (e.g. randomized controlled trials) and there is uniform NCCN consensus.
  • Category 2A: The recommendation is based on lower level evidence and there is uniform NCCN consensus.
  • Category 2B: The recommendation is based on lower level evidence and there is nonuniform NCCN consensus (but no major disagreement).
  • Category 3: The recommendation is based on any level of evidence but reflects major disagreement.

In June 2008, the NCCN Compendium became one of four references for the Centers for Medicare & Medicaid Services (CMS) for oncology coverage policy.

In its national coverage decision, CMS states that, in general, a use identified by the NCCN Compendium is medically accepted if the indication is a Category 1 or 2A as defined by NCCN. A use is not medically accepted if the indication is a category 3 in NCCN.

The local CMS contractor, Noridian Administrative Services (NAS), has issued an additional coverage statement regarding Category 2B:

“NAS recognizes NCCN Categories of Evidence Levels Category 1 and Category 2A ONLY as medically accepted indications. If a provider chooses to use NCCN level 2B in support of a chemotherapeutic drug used off-label in an anti-cancer chemotherapeutic regimen, NAS expects that the provider will make available to NAS significant peer-reviewed Phase II or Phase III studies demonstrating such support. In the absence of such studies, level 2B evidence does not support such use.”

The following policy considers only the off-label indications for rituximab and atumumab.

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer services representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application

State or federal mandates regarding off-label uses of drugs approved by the U.S. Food and Drug Administration (FDA) may supersede this policy.

Rationale

Rituximab (Rituxan®)

  • Regarding rituximab for patients with intermediate or aggressive non-Hodgkin’s lymphoma (NHL), an interim analysis of a randomized controlled trial is available in abstract form. The trial compared rituximab plus combination chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone, aka CHOP) to CHOP therapy alone in 400 patients with previously treated diffuse large B-cell lymphoma. By intent–to-treat analysis, event-free and overall survival at 12 months was superior in the rituximab plus CHOP arm. In 2002, final results of this trial were published by Coiffier et al, confirming the superior outcomes in the combination arm. In the Coiffier study, event-free survival at 2 years (CI 95%) was 57% in the CHOP + Rituximab arm and 38% in the CHOP alone arm. A 2002 TEC Assessment also found Rituximab met criteria for treatment of patients with intermediate or aggressive B-cell non-Hodgkin’s lymphoma based on the Coiffier study.
  • In a randomized, phase III trial of 122 patients with untreated advanced-stage mantle cell lymphoma, Lenz and colleagues reported patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) plus rituximab (n=62) had significantly superior outcomes than patients receiving CHOP alone (n=60). Complete response rates and median time to treatment failure in the CHOP plus rituximab group vs the CHOP alone group were 34% vs 7% (p=0.00024) and 21 months versus 14 months (p=0.0131), respectively. Toxicities were reported to be acceptable and similar in both treatment groups.

The indications for off-label use of rituximab were determined by:

  • Considering the limited but evolving evidence in clinical trials indicating that CD20 expression enhanced susceptibility to this drug, and thus a response was more likely;
  • Soliciting the expert opinion of physician specialists on its accepted use; and
  • National Comprehensive Cancer Network Clinical Practice Guidelines for Non-Hodgkin’s Lymphomas.

Ofatumumab (Arzerra®)

  • The evidence for efficacy and safety of ofatumumab is currently limited to uncontrolled clinical studies. This evidence suggests ofatumumab is efficacious for achieving an objective response in approximately 50% patients with fludrabine- or alemtuzumab-refractory CLL.
  • The drug also appears to have efficacy in some patients with rituximab-refractory disease.
  • Controlled clinical trials are needed to establish the superiority of ofatumumab over other therapeutic alternatives (e.g., rituximab). In addition, improved survival remains to be established.

2004 Update

The U.S. Pharmacopoeial Convention (2003) has concluded that rituximab (Rituxan) is accepted for the following off-label indications: a) as first-line treatment of diffuse aggressive NHL; b) treatment of relapsed or refractory diffuse aggressive NHL; c) first-line treatment of intermediate to high-grade NHL; and d) first-line treatment of low-grade NHL.

2006 Update

Studies continue, but have not yet been published, which would indicate the safety and efficacy of Mylotarg® as a single-agent treatment for patients who are CD33-positive with AML in first relapse. Outcomes of these studies are awaited.

2008 Update

NCCN guidelines v.3.2008 recommends rituximab (preferred), or alkylating agents such as cyclophosphamide or chlorambucil as single agents for first-line therapy for follicular lymphoma in elderly or infirm patients.

2009 Update

Both R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) have been used successfully in the treatment of patients with symptomatic follicular lymphoma (FL). Ganguly and Patel (2009 conducted a meta-analysis of relevant literature comparing both treatment arms for FL with response being the final endpoint. Two analyses were conducted: The first analysis compared R-CHOP to R-CVP as frontline agents for the treatment of FL and the second analysis included both untreated and relapsed patients. The authors report that for both studies, R-CVP was superior to R-CHOP when evaluating for complete response (CR). However for overall response (CR+PR), R-CHOP was superior. The authors concluded that both R-CHOP and R-CVP protocols achieve excellent overall response. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive CR rate. In younger patients with FL where cumulative cardio-toxicity may be of importance in the long term and in whom future stem cell transplantation is an option, again R-CVP may be a more appealing option.

The Company recognizes uses of rituximab, ofatumumab, , and alemtuzumab listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence and Consensus of 1 and 2A as proven and Categories of Evidence and Consensus of 2B and 3 as unproven. However, Category 2B uses may be considered for coverage if they are substantiated by provider submission of significant peer-reviewed Phase II or Phase III studies demonstrating treatment effectiveness.

2010 Update

Updated to reflect current NCCN Compendium recommendations as of February 2010. Added newly marketed anti-CD20 monoclonal antibody, ofatumumab. Added information concerning the voluntary withdrawal of gemtuzumab from the market.

2011 Update

Policy updated with literature review. Policy statements for Mylotarg® and supporting data removed from policy statement and any reference throughout the policy subsequent to FDA withdrawal of approval for this drug.

2012 Update

Policy updated to include NCCN recommendation for treatment of leptomeningeal metastases. (Category 2A) These may occur with various solid tumors, breast and lung being the most common. Therapy is palliative and usually of limited duration, as the average life expectancy of these patients is only a few weeks.

2013 Update

Policy updated to include NCCN recommendation for addition of rituximab in induction/consolidation treatment of , ALL, CLL/SLL, primary CNS lymphomas, AIDS-related B-cell lymphoma, follicular lymphoma, hairy cell leukemia, and lymphoblastic lymphoma. (Category 2A and above) Also treatment of post-transplant lymphoproliferative disorder. (Category 2A)

Added Ofatumumab (Arzerra) NCCN recommended off-label use for Waldenstrom’s macroglobulinemia. (Category 2A)

Alemtuzumab (Campath) removed from policy as it is no longer commercially available.

References

  1. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Off- label uses of monoclonal antibodies for treatment of B-cell lymphoid or myeloid malignancies. TEC Assessments 2001; Tab 7.
  2. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med 2002; 346(4):235-42.
  3. 2002 TEC Assessment; Tab 3, Rituximab for treatment of intermediate or aggressive B-cell non-Hodgkin’s lymphoma.
  4. Lundin J, Kimby E, Bjorkholm M et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100(3):768-73.
  5. Lang K, Menzin J, Erle CC et al. Outcomes in patients treated with gemtuzumab ozogamicin for relapsed acute myelogenous leukemia. Am J Health Syst Pharm 2002; 59(10):941-8.
  6. Hainsworth JD, Litchy S, Burris HA 3rd et al Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin’s lymphoma. J Clin Oncol 2002; 20(20):4261-7.
  7. Hainsworth JD, Litchy S, Barton JH et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21(9):1746-51.
  8. Reyes F (Ed). Multiple applications of Rituximab in optimizing therapy for non-Hodgkin’s Lymphoma. Semin Oncol 2004; 31(No. 1, suppl 2):1-37.
  9. U.S. Pharmacopeial Convention, Inc. Finalized Drug Information. [Website]. Rockville, MD: U.S. Pharmacopeia; 2003. Last accessed September 30, 2013.
  10. Kell WJ, Burnett AK, Chopra R et al. A feasibility study of simultaneous administration of Gemtuzumab Ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood. 2003 15; 102(13):4277-83.
  11. Erba HP. Treatment options for newly diagnosed patients with chronic lymphocytic leukemia. Curr Hematol Rep. 2004; 3(1):47-53.
  12. Lenz G, Dreyling M, Hoster E et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone significantly improves response time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005; 23(9):1984-92.
  13. Marcus R, Imrie K, Belch A et al. CVP Chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005; 105(4):1417-23.
  14. Habermann TM, Weller EA, Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121-7.
  15. Wendtner CM, Rigen M, Schweighofer CD et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission – experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia. 2004;18(6):1093-101.
  16. Tauro S, Craddock C, Peggs, K et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remission and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. Clin Oncol. 2005;23(36):9387-93. Epub 2005 Nov 28.
  17. van Besien K, Artz A, Smith S et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplatic syndrome. J Clin Oncol. 2005;23(24):5728-38. Epub 2005 Jul 11.
  18. Fiegl M, Falkner A, Hopfinger G et al. Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia: Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria. Cancer 2006; 107(10):2408-16.
  19. Elter T, Borchmann P, Schulz H et al. Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: Results of a phase II trial. J Clin Oncol 2005;23 (28):7024-31. Epub 2005 Sept 6.
  20. Tam CS, Wolf M, Prince HM et al. Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma. Cancer 2006;106 (11):2412-20.
  21. Swords R, Nolan A, Fay M et al. Treatment of refractory fludarabine induced autoimmune haemolytic with the anti-CD20 monoclonal antibody rituximab. Clin Lab Haematol 2006;28(1):57-9.
  22. Byrd JC, Gribben JG, Peterson BL et al. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol 2006;24(3):437-43. Epub 2005 Dec 12.
  23. Taksin AL, Legrand O, Raffoux E et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alpha group. Leukemia 2007;21(1):66-71. Epub 2006 Oct 19.
  24. Sekeres MA. Non-transplant therapy for older adults with acute myeloid leukemia. J Natl Compr Canc Netw 2006;4(1):51-6. Review.
  25. Fenton C, Perry CM. Gemtuzumab ozogamicin: a review of its use in acute myeloid leukemia. Drugs 2005;65(16):2405-27. Review.
  26. Reviewed and recommended for adoption by the Pharmacy & Therapeutics Committee, September 26, 2006; May 27, 2008; and March 30, 2010.
  27. Reviewed and recommended for adoption by Oncology Advisory Panel, February 22, 2007; May 22, 2008; and May 19, 2010.
  28. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Non-Hodgkin’s Lymphomas. V.3.2008.
  29. Ghielmini M, Hsu, Schmitz SF, Cogliatti SB; et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004; 103:4416-23.
  30. National Comprehensive Cancer Network. The NCCN Drugs and Biologics Compendium. Last accessed September 30, 2013.
  31. Ganguly S, Patel V. R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature. J Hematol Oncol 2009;Mar 24;2(1):14.
  32. Coiffier B, Lepretre S, Pedersen LM et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008; 111:1094-1100.
  33. Wierda W, Kipps T, Mayer J et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia 2010 (In press).
  34. Wierda WG, Kipps TJ, Durig J et al. Ofatumumab combined with fludarabine and cyclophosphamide (O-FC) shows high activity in patients with previously untreated chronic lymphocytic leukemia (CLL): results from a randomized, multicenter, international, two-dose, parallel group, phase II trial [abstract]. Blood 2009; 114:207.
  35. Hagenbeek A, Gadeberg O, Johnson P et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 2008; 111:5486-5495.
  36. FDA News Release: Pfizer Voluntarily Withdraws Cancer Treatment Mylotarg from U.S. Market. June 21, 2010. Last accessed September 30, 2013.

Coding

Codes

Number

Description

CPT

96409

Chemotherapy administration; intravenous, push technique, single or initial substance/drug

 

96413

Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug

 

96415

each additional hour (list separately in addition to code for primary procedure

 

96417

each additional sequential infusion (different substance/drug), up to 1 hour (List separately in addition to code for primary procedure)

ICD-9 Procedure

   

ICD-9 Diagnosis

200.10

Lymphosarcoma , unspecified site, extranodal and solid organ sites

 

200.11

lymph nodes of head, face and neck

 

200.12

intrathoracic lymph nodes

 

200.13

intra-abdominal lymph nodes

 

200.14

lymph nodes of axilla and upper limb

 

200.15

lymph nodes of inguinal region and lower limb

 

200.16

intrapelvic lymph nodes

 

200.17

spleen

 

200.18

lymph nodes of multiple sites

 

202.00

Nodular lymphoma, unspecified site, extranodal and solid organ sites

 

202.01

lymph nodes of head, face and neck

 

202.02

intrathoracic lymph nodes

 

202.03

intra-abdominal lymph nodes

 

202.04

lymph nodes of axilla and upper limb

 

202.05

lymph nodes of inguinal region and lower limb

 

202.06

intrapelvic lymph nodes

 

202.07

spleen

 

202.08

lymph nodes of multiple sites

 

204.10

Chronic lymphoid leukemia, without mention of having achieved remission

 

204.11

in remission

 

205.10

Acute myeloid leukemia, without mention of having achieved remission

 

205.11

in remission

 

273.3

Macroglobulinemia (Waldenstrom’s Syndrome)

HCPCS

J9302

Injection, ofatumumab, 10 mg (Arzerra)

 

J9310

Injection, rituximab, 100 mg (Rituxan)

 

J9999

Not otherwise classified, antineoplastic drug (ofatumumab)

Type of Service

Oncology

 

Place of Service

Outpatient

 

Appendix

N/A

History

Date

Reason

08/15/01

Add to Medicine Section - New Policy

08/13/02

Replace Policy - Policy revised; policy statement changed regarding Rituximab for intermediate or aggressive NHL.

07/13/04

Replace Policy - Policy revised with literature updated; added the 2004 US Pharmacopeia and the American Hospital Formulary Service off-label indications to the Benefit Application section; clarification made: mantle cell was removed from investigational status; otherwise, policy statement unchanged.

12/14/04

Replace Policy / New Policy - Policy replaces BC.2.03.05 per direction from OAP 10/29/04 meeting. Indications changed from investigational to medically necessary.

10/11/05

Replace Policy - Scheduled reviewed. Added two off-label indications to Rituximab in policy statement.

02/06/06

Codes updated - No other changes.

06/23/06

Update Scope and Disclaimer - No other changes.

12/12/06

Replace Policy - Policy reviewed by P&T Committee on September 26, 2006; policy statement expanded to include the use of Alemtuzumab (CamPath®) in the treatment of malignancies other than CLL that express CD-52 antigen as a medically necessary indication; and the use of Gemtuzumab ozogamicin (Mylotarg®) in the treatment of malignancies other than CLL which express CD-33 antigen as a medically necessary indication; malignancies other than CD33-positive remain investigational, but the condition of AML has been removed from this particular statement indication.

02/22/07

Update References - Policy reviewed and recommended by OAP February 22, 2007. No change to policy statement.

04/10/07

Replace Policy - Policy Guidelines amended to indicate that Mylotarg is intended for IV administration.

06/10/08

Replace Policy - Policy updated with literature search. Policy statement under Rituxan updated to include: “Therapy of other B-cell malignancies that express CD-20 antigen including some cases of CD-20 positive Hodgkin’s Disease and Monotherapy as first-line follicular lymphoma treatment for elderly patients, or others who are not good candidates for cytotoxic chemotherapy” as a medically necessary indication. Policy reviewed and recommended by OAP May 22, 2008. P&T reviewed and approved on May 27, 2008.

02/10/09

Code Update - Code 273.3 added; no other changes.

05/12/09

Replace Policy - Policy statements revised to clarify off-label uses. Intent of policy remains unchanged. NCCN categories of evidence added to Description and Rationale. References added.

10/13/09

Cross Reference Update - No other changes.

05/11/10

Cross Reference Update - No other changes.

08/10/10

Replace Policy - Policy updated the Rituximab labeled indications reflecting the latest revision (02/2010) by deleting all the references to the other chemotherapy agents.Reviewed and recommended by P&T in March 2010; by OAP in May 2010. Mylotarg removed. Arzerra added.

07/12/11

Replace Policy - Policy updated with literature review. Policy statements for Mylotarg® and supporting data removed from policy statement and any reference throughout the policy subsequent to FDA withdrawal of approval for this drug. No change to policy statements.

10/19/11

Related Policy 5.01.01 added.

09/11/12

Replace policy. Policy updated with literature review. CD-20 positive leptomenigeal metastases added to the list of approved off-label indications for rituximab.

11/26/12

Related Policies Update, add 5.01.526.

10/14/13

Replace policy. Within the Policy section, additional examples of off-label indications for Rituxan® have been added to the list of those considered medically necessary; Azerra® has an added medically necessary indication for salvage treatment of Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic lymphoma in rituximab-intolerant patients; and Campath® has been removed from the policy as it is no longer commercially available. Description, Policy Guidelines and Rationale sections updated in support of the changes within the Policy section. HCPCS code J9010 for Campath removed from the coding section.

11/20/13

Update Related Policies. 5.01.01 deleted and replaced with 5.01.549.

12/18/13

Update Related Policies. Change title to 5.01.526.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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