Clinical UM Guideline

 

Subject: Brentuximab Vedotin (Adcetris®)
Guideline #: CG-DRUG-106 Publish Date:    02/27/2019
Status: Revised Last Review Date:    01/24/2019

Description

This document addresses indications and criteria for use of brentuximab vedotin (Adcetris, Seattle Genetics, Bothell, WA), an antibody-drug conjugate (ADC) that combines a small molecule chemotherapeutic agent (monomethyl auristatin E [MMAE]) with a chimeric IgG1 antibody that binds to the CD30-positive cells (CD30+).

Clinical Indications

Medically Necessary:

  1. Brentuximab vedotin is considered medically necessary for the treatment of individuals with Hodgkin lymphoma with any of the following indications:
    1. Previously untreated stage III or IV classical Hodgkin lymphoma, in combination with doxorubicin, vinblastine, and dacarbazine; or
    2. For relapsed or refractory disease in a single line of therapy as a single agent or in combination with bendamustine; or
    3. As consolidation therapy after an autologous stem cell transplantation for individuals at high risk of relapse or progression, that is, individuals with any of the following:
      1. Primary refractory Hodgkin lymphoma; or
      2. Relapsed Hodgkin lymphoma with an initial remission duration of less than 12 months; or
      3. Extranodal involvement at the start of pre-transplantation salvage chemotherapy; or
    4. As maintenance therapy for 1 year following high-dose therapy and autologous stem cell rescue for relapsed or refractory disease in those who are brentuximab vedotin naïve and have a Deauville score of less than 5.
  2. Brentuximab vedotin is considered medically necessary for the treatment of individuals diagnosed with CD30+ non-Hodgkin lymphoma with any of the following indications:
    1. Cutaneous anaplastic large cell lymphoma; or
    2. Cutaneous T-cell lymphoma, including mycosis fungoides/Sézary syndrome which is relapsed, refractory or as first-line therapy for advanced disease presentation (for example, folliculotropic, large-cell transformation or extracutaneous disease); or
    3. Previously untreated peripheral T-cell lymphoma in combination with cyclophosphamide, doxorubicin, and prednisone; or
    4. Relapsed or refractory disease after at least one prior multi-agent chemotherapy regimen for treatment of any of the following:
      1. Systemic anaplastic large cell lymphoma; or
      2. T-cell lymphoma (excluding cutaneous T-cell lymphoma); or
      3. Lymphomatoid papulosis that is symptomatic or characterized by extensive cutaneous lesions; or
    5. As a single-agent for adult T-cell leukemia/lymphoma after high dose therapy and autologous stem cell rescue; or
    6. As an adjuvant systemic therapy for breast implant-associated anaplastic large cell lymphoma for either of the following:
      1. Residual, localized disease (confined to capsule/implant/breast) following partial excision or capsulectomy; or
      2. Extended disease (stage II–IV).

Not Medically Necessary:

Brentuximab vedotin is considered not medically necessary when the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J9042

Injection, brentuximab vedotin, 1 mg [Adcetris]

 

 

ICD-10 Diagnosis

 

C81.00-C81.99

Hodgkin lymphoma

C84.00-C84.19

Mycosis fungoides, Sézary disease

C84.40-C84.49

Peripheral T-cell lymphoma, not classified

C84.60-C84.69

Anaplastic large cell lymphoma, ALK-positive

C84.70-C84.79

Anaplastic large cell lymphoma, ALK-negative

C84.A0-C84.A9

Cutaneous T-cell lymphoma, unspecified

C84.Z0-C84.Z9

Other mature T/NK-cell lymphomas

C86.1

Hepatosplenic T-cell lymphoma

C86.2

Enteropathy-type (intestinal) T-cell lymphoma

C86.5

Angioimmunoblastic T-cell lymphoma

C86.6

Primary cutaneous CD30-positive T-cell proliferations

C91.50-C91.52

Adult T-cell lymphoma/leukemia (HTLV-1-associated)

Z85.71

Personal history of Hodgkin lymphoma

Z85.72

Personal history of non-Hodgkin lymphomas

Discussion/General Information

A monoclonal antibody is a protein developed in the laboratory that can locate and bind to a targeted substance in the body and on the surface of cancer cells.  These antibodies can carry drugs, toxins, or radioactive substances to the targeted cancer cells (National Cancer Institute [NCI], 2018). Brentuximab vedotin is a novel ADC that combines a monoclonal antibody which targets CD30+ cells with MMAE, a cytotoxic antimicrotubule.  Once the ADC is attached to CD30+ cells, the MMAE disrupts the microtubule network resulting in death of the cell.

The United States (U.S.) Food and Drug Administration (FDA) granted accelerated drug approval for brentuximab vedotin (Adcetris) on August 19, 2011.  The labeled indications included brentuximab as monotherapy for relapsed or refractory Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens when individuals were ineligible for transplant.  Additionally, brentuximab was approved as a treatment for systemic anaplastic large cell lymphoma (ALCL) after failure of at least one prior multi-agent regimen.  In 2015, the label was expanded to include treatment as a consolidation therapy for classical HL at high risk of relapse or progression after auto-HSCT (Younes, 2012).  In 2017, the label was again expanded to include primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy, and in 2018 to include previously untreated stage III or IV classical Hodgkin lymphoma, in combination with doxorubicin, vinblastine, and dacarbazine as well as CD30-expressing peripheral T-cell lymphomas (PTCL) in combination with cyclophosphamide, doxorubicin, and prednisone (Product Information [PI] Label, 2018).

Hodgkin Lymphoma

HL is a type of malignancy which starts in the lymphocytes, a type of white blood cell that fights infection.  HL most commonly affects people between the ages of 15 and 40 and people older than age 55.  According to recent estimates 8500 new cases of Hodgkin lymphoma are diagnosed annually in the US and 1050 will succumb to the disease (NCI, 2018).  In HL, cells in the lymphatic system grow abnormally and may spread beyond the lymphatic system.  As the disease progresses, it compromises the body's ability to fight infection.  Many initial signs and symptoms may be similar to those of influenza, such as fever, fatigue and night sweats.  Eventually, tumors develop.  There are two main classifications of HL: lymphocyte-predominant Hodgkin lymphoma (LPHL) and classical Hodgkin lymphoma (CHL) (American Cancer Society [ACS], 2018; National Comprehensive Cancer Network® [NCCN], 2018).  CHL is distinguished by the presence of abnormal Reed-Sternberg cells which express CD15 and CD30 in a majority of the cases, with CD20 expression occurring at a lower rate.  In developed countries, CHL accounts for approximately 95% of all Hodgkin disease (ACS, 2018).  LPHL accounts for approximately 5% of all HL cases, usually expressing CD45 and CD20.  In LPHL, lymphocyte predominant cells, also called "popcorn cells" are present in the lymphoma tissue instead of the Reed-Sternberg cells (NCCN, 2018).

The NCI (2018) and NCCN (2018) report chemotherapy and radiation therapy may cure more than 75% to 80% of all newly diagnosed Hodgkin disease cases.  Autologous or allogeneic hematopoietic stem cell transplantation is recognized as the best option for refractory or relapsed Hodgkin disease in individuals who meet the criteria for transplantation.  Advances in diagnosis, staging and treatment of Hodgkin disease have helped to make this once uniformly fatal disease highly treatable with the potential for full recovery.  The national mortality rate for adult Hodgkin lymphoma has fallen more rapidly than for any other malignancy.  Approximately 30% to 40% of individuals with advanced HL are refractory to initial therapy or will relapse despite advances in front-line treatment (Deutsch, 2011).

In 2012, a multi-national, open label, single-arm clinical trial was conducted that included 102 individuals with relapsed or refractory HL after an auto-HSCT who were treated with brentuximab vedotin.  The primary endpoint was overall response rate (ORR) which was 73% with a median duration of response of 6.7 months (range, 1.3 to 21.9 months).  Complete response (CR) was 32% with a median duration of response of 20.5 months (range, 1.4 to 21.9+ months).  Partial response (PR) was 40% with a median duration of 3.5 months (range 1.3 to 18.7 months) (PI Label, 2016; Younes, 2012).  The safety and efficacy of brentuximab vedotin after a failed auto-HSCT or after at least two prior multi-agent chemotherapy regimens in individuals who are not AHSCT candidates, have been demonstrated and are included as FDA approved labeled indications.

In 2018 Connors and colleagues published results of the Phase III ECHELON-1 clinical trial (n=1334) which evaluated brentuximab vedotin + AVD (adriamycin, vinblastine, dacarbazine) (n=664) compared to ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) (n=670).  The trial’s primary endpoint was modified progression-free survival (PFS) and the main secondary endpoint was ORR.  Key eligibility criteria included 18 years or older, confirmed advanced classic HL (Ann Arbor stage III or IV) treatment naive and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.  The trial met its primary endpoint.  With a median follow-up of 24.6 months, the PFS rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8-85.0) and 77.2% (95% CI, 73.7-80.4), respectively, (hazard ratio [HR]=0.77; 95% CI, 0.60-0.98; p=0.04).  In total, 28 deaths occurred in the A+AVD group and 39 in the ABVD group.  Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were neutropenia-related and 11 of 13 in the ABVD group were related to pulmonary-related toxicity.  The A+AVD group, compared to the ABVD group had a higher occurrence of neutropenia (58% versus 45%, respectively) and peripheral neuropathy (67% versus 43%, respectively); 67% of those in the A+AVD group who had peripheral neuropathy had resolution or improvement by study-end.  Grade 3 or higher pulmonary toxicity was reported in less than 1% of participants receiving A+AVD and in 3% of those receiving ABVD.  Based on the safety and efficacy demonstrated in this trial the FDA expanded the labeled indications for brentuximab vedotin to include previously untreated stage III or IV classical Hodgkin lymphoma, in combination with doxorubicin, vinblastine, and dacarbazine (FDA PI Label, 2018).

The NCCN Hodgkin Lymphoma Clinical Practice Guideline ([CPG] 2018) notes for those individuals with progressive disease after high-dose therapy and autologous stem cell rescue (HDT/ASCR) or at least two prior chemotherapy regimens, brentuximab vedotin is a treatment option.  This recommendation was based on a 2A category of evidence and uniform NCCN consensus.  

There are retrospective case series that reported limited data on the use of brentuximab vedotin to treat individuals with refractory or relapsed Hodgkin disease prior to autologous and allogeneic hematopoietic stem cell transplantation (Chen, 2012; Chen 2014; Sasse, 2013).  Additionally, NCCN has given brentuximab vedotin a 2A recommendation for cytoreduction prior to an auto-HSCT and as treatment after relapse from prior therapy based on an abstract in 30 evaluable individuals (Chen, 2014).

The use of brentuximab vedotin as consolidation therapy for individuals with unfavorable risk of relapse or progression of HL after auto-HSCT was studied in a phase III double-blind, randomized controlled trial (RCT) called AETHERA (Moskowitz, 2015).  Inclusion criteria required the participants to have one of the following risk factors: “Primary refractory HL (failure to achieve complete remission, as determined by investigator), relapsed HL with an initial remission duration of less than 12 months, or extranodal involvement at the start of pre-transplantation salvage chemotherapy.”  Individuals were randomized at 78 North American and European centers to receive 16 cycles of brentuximab vedotin every 3 weeks beginning 30-45 days after AHSCT.  The primary endpoint was PFS assessed by independent reviewers.  A total of 329 individuals were enrolled and 165 participants were randomized to brentuximab vedotin treatment and 164 individuals were assigned to the placebo group.  Computerized tomography (CT) scans were performed at baseline and repeated after the first dose of study drug at 3, 6, 9, 12, 18 and 24 months.  The median follow-up was 30 months (range, 0-50 months).  Median PFS was significantly improved in those treated with brentuximab vedotin; 42.9 months (95% CI; 30.4-42.9 months) compared to those who received placebo 24.1 months (95% CI; 11.5 –not estimable months).  In August of 2015, the FDA expanded the label based on the AETHERA trial to include treatment for CHL when the risk of relapsed or refractory disease is high following an auto-HSCT.

The NCCN published updated CPGs for HL (2018) with an NCCN 2A recommendation for use of brentuximab as maintenance therapy for 1 year following high-dose therapy and auto-HSCT for relapsed or refractory disease in those who are brentuximab naïve.  This recommendation was based on the previously discussed AETHERA trial, which investigated 48 weeks of consolidation therapy in this population (Moskowitz, 2015).  An additional NCCN 2A recommendation was added to the HL CPGs for use of brentuximab as palliative therapy for relapsed or refractory disease in older adults, 60 years of age or older.  This recommendation is based on a 2014 abstract of 36 individuals who were an average age of 34 years (Chen, 2014).

There is an NCCN 2A recommendation for use of brentuximab vedotin for HL in combination with several chemotherapy regimens; however, these regimes are not in accordance with generally accepted standards of medical practice. There is published peer-reviewed evidence of combination use of brentuximab vedotin with bendamustine.  In a phase I/II clinical trial, 55 relapsed/refractory HL cases were enrolled and treated with brentuximab vedotin and bendamustine as first salvage therapy.  The ORR was 93% with 39 individuals (74%) achieving a CR.  At a median of 20.9 months follow-up, the estimated 2-year PFS was 69.8% for those who had subsequently received an auto-SCT and 63% overall.  A total of 56% of individuals experienced an infusion-related reaction prior to a protocol amendment requiring premedication to reduce severity of adverse reactions.  A total of 3 deaths occurred in the study, 1 of septic shock during stem cell transplant and 2 from progressive disease; none were deemed to be treatment-related and all occurred at least 30 days post treatment (LaCasce, 2018).

Non-Hodgkin Lymphoma

NHLs are a group of malignancies with varying patterns of disease course and treatment responses.  Similar to HL, NHL usually originates in lymphatic tissue and spreads to other organs. However, unlike HL, NHL is less predictable and therefore less treatable.  Prognosis is based on a number of factors including histology and stage.  In 2018 an estimated 73,000 new cases of NHL will be diagnosed in the U.S. and 20,000 will die from the disease (NCI, 2018).  NHLs are divided into two prognostic groups, indolent and aggressive lymphomas.

Peripheral T-cell lymphoma (PTCL) is a subtype of NHL that develops from mature T-cells of post-thymic origin and constitutes a mixed group of lymphoproliferative disorders (LPDs).  Subtypes of PTCL include PTCL-NOS, the most common subtype, and less frequently, angioimmunoblastic T-cell lymphoma (AICL) and anaplastic large cell lymphoma (ALCL) which expresses CD30 (NCCN, 2019).

Primary cutaneous ALCL has an indolent course with frequent relapses typically limited to the skin and very good long-term survival.  Combination therapy is rarely indicated for primary cutaneous ALCL.  Standard induction therapy for ALK-positive ALCL is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy and radiation therapy (RT).  NCCN clinical practice guidelines (2018) note it is “critical to distinguish CD30+ T-cell LPDs [such as MF/SS] from other CD30+ processes involving the skin that includes: systemic lymphomas (e.g., systemic ALCL, adult T-cell leukemia/lymphoma [ATLL], PTCL).” 

Peripheral T-Cell Lymphoma (PTCL)

In November of 2018, the brentuximab vedotin FDA PI label was updated to include the following expansion, “Previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone”.  Approval was based on the ECHELON-2 clinical trial, a double-blind, multicenter, randomized study that enrolled 226 individuals with previously untreated CD30+ PTCLs to receive brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) and 226 to receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).  Efficacy was based on median PFS which was 48.2 months for the brentuximab vedotin + CHP arm and 20.8 months for the CHOP arm (HR=0.71; p=0.011).  The secondary outcome of overall survival (OS) was also significantly better in the brentuximab arm (p=0.024), as was complete response rates (68% vs 56%, p=0.007), and ORR (83% vs 72%, p=0.003).  Adverse events were similar between the study arms and fatal adverse events occurred in 7 (3%) individuals in the brentuximab vedotin + CHP arm and 9 (4%) in the CHOP group (Horwitz, 2018).

Anaplastic Large Cell Lymphoma (ALCL)

ALCL is a subtype of mature PTCL NHL that involves less than 5% of all NHL cases.  There are three subtypes of ALCL: anaplastic lymphoma kinase (ALK)-positive ALCL, ALK-negative ALCL, and primary cutaneous ALCL.  CD30 is a strong diffuse expression in those with ALCL (NCCN, 2019).

A phase II, single-arm, multicenter, open label clinical trial studied 58 individuals with relapsed systemic ALCL treated with brentuximab.  Participants had a median of two prior therapies and 26% had received prior AHSCT.  The majority (72%) of the participants were ALK-negative.  Of the 58 study participants, 50% had relapsed disease and 50% were refractory to recent therapy.  Median duration of treatment was 24 weeks (range, 3 to 56 weeks).  ORR was 86% with a median duration of response of 12.6 months (range, 0.1 to 15.9+ months).  CR was 57% with a median duration of response of 13.2 months (range, 0.7 to 15.9+ months).  With a median duration of 2.1 months (range, 0.1, to 15.8 months), PR was 29% (PI Label, 2016).  The most commonly reported adverse events (grade 3-4) included neutropenia (21%), thrombocytopenia (14%) and peripheral sensory neuropathy (10%) (Pro, 2012; Shustov, 2011).  Five-year follow-up of this cohort examined the durability of remission, PFS, OS, and safety outcomes of participants treated in this trial.  Among all those enrolled (n=58), no progressions were observed beyond 40 months, and median OS was not reached.  Those study participants who had a CR continued to demonstrate improved outcomes with neither median OS nor PFS reached.  Peripheral neuropathy was experienced in 33 participants; however the majority (30 of 33) had resolution or improvement at their last assessment.  These results demonstrate durable remissions for individuals with relapsed or refractory systemic ALCL, treated with single-agent brentuximab vedotin (Pro, 2017).

The NCCN CPG for T-Cell Lymphomas (2019) recommends brentuximab vedotin as a treatment for individuals with relapsed or refractory systemic ALCL (excluding cutaneous ALCL) as second-line or subsequent therapy based on three phase II clinical trials that included this population (Horwitz 2014; Pro 2012; Pro 2013).  There is also a 2A recommendation for breast-implant associated large cell lymphoma as adjuvant therapy for localized disease following incomplete excision or partial capsulectomy with residual disease, or for extended disease (stage II-IV).  Only anecdotal case reports are cited (Alderuccio, 2018; Johnson, 2017).

Cutaneous ALCL

The efficacy of brentuximab vedotin in individuals with pcALCL or MF requiring systemic therapy was studied in ALCANZA, a phase III, randomized, open-label, multicenter clinical trial.  Participants enrolled had CD30+ confirmed disease, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and had previously received at least one prior systemic therapy.  Investigators randomized 131 individuals (1:1) to receive either brentuximab or physician’s choice of methotrexate or bexarotene.  Efficacy was established based on improvement in objective response rate lasting 4 months (ORR4; primary endpoint), complete response (CR) rate, and PFS.  The study’s primary endpoint was achieved with a clinically and statistically significant improvement (p<0.001) demonstrated by the ORR4 in the brentuximab vedotin arm (56%; 95% CI, 44-68%) versus the physician’s choice arm (12%; 95% CI, 4-21%).  CR rate was also superior (p=0.007) in the brentuximab vedotin arm 16% (95% CI, 8-27%) versus the physician’s choice arm (2%; 95% CI 0-8%).  Improvement in PFS was also achieved with an estimated HR of 0.27 (95% CI, 0.17-0.43; p<0.001); PFS was17 months in the brentuximab vedotin arm versus 4 months in the physician’s choice arm.  Grade 3-4 adverse events were reported in 27 (41%) of 66 participants in the brentuximab group and 29 (47%) of 62 participants in the physician’s choice group.  Peripheral neuropathy was reported in 44 (67%) of 66 enrolled in the brentuximab group (n=21 grade 2, n=6 grade 3) and 4 (6%) of 62 enrolled in the physician’s choice group.  Only 1 of the 4 deaths in the brentuximab group was deemed to be treatment-related; no on-treatment deaths were reported in the physician’s choice group.  Over the duration of the follow-up period (median of 22.9 months) 16 (24%) deaths occurred in the brentuximab group and 14 (23%) in the physician’s choice group.  The most common adverse reactions occurring in > 20% of individuals who received brentuximab were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia (Prince, 2017).  In 2017, the FDA expanded the labeled indications for brentuximab vedotin to include primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy based on this clinical trial.

Other T-Cell Lymphomas and Lymphoproliferative Disorders

There is an NCCN 2A recommendation for the second-line treatment of systemic CD30+ PTCL subtypes.  The recommendation is based on Phase II open-label trials which included angioimmunoblastic T-cell lymphoma (AITL), PTCL-not otherwise specified (PTCL-NOS), and ALCL subtypes (Horwtiz, 2014; Pro, 2012; Shustov, 2011).

Until recently, there were only case reports and small case series reporting outcomes of brentuximab vedotin to treat lymphomatoid papulosis (LyP).  The NCCN guidelines for T-Cell Lymphomas (2018) include 2A off-label indications for brentuximab to treat LyP.  These recommendations are supported in a study by Duvic and colleagues (2015).  A total of 48 individuals with heavily pretreated CD30+ lymphoproliferative disorders or mycosis fungoides (MF) were enrolled and administered brentuximab vedotin every 21 days. In the study, 28 of the 48 evaluable study participants had MF/SS with an ORR of 54% (n=13 PR; n=2 CR) and 9 had LyP with an ORR of 100% (n=5 CR; n=4 PR).  The most frequently reported grade 3 and 4 adverse event was neutropenia (n=5).  Another Phase II clinical trial conducted by Kim and colleagues (2015) evaluated brentuximab in 30 individuals with MF/SS.  In this heavily pre-treated cohort with a wide range of CD30 expression levels and advanced disease states, high response rates were achieved.  The primary study endpoint, overall global response rate, was 70% (n=21; 90% CI, 53-83%).  CD30 expression level in cutaneous lesions (from negligible to 100% expression) was significantly associated with the likelihood of global response (p<0.005).  Similar to Duvic’s (2015) findings, the most commonly reported adverse event was peripheral neuropathy; 1 case was so severe it resulted in pneumonia and ultimately death.  In this rare, difficult to treat disease, brentuximab vedotin has demonstrated efficacy with a tolerable safety profile and is in accordance with generally accepted standards of medical practice.

B-Cell Lymphomas

In 2018, NCCN upgraded their recommendation for relapsed/refractory CD30+ diffuse large B-cell lymphoma (DLBCL) for individuals who are not candidates for a transplant from a 2B recommendation to a 2A recommendation, but no rationale has been provided in support of this amendment and is not it is not generally considered clinical appropriate.  At this time, there is only a 2015 phase II open-label trial with a subset analysis of participants with relapsed/refractory CD30+ DLBCL (n=49) that reported the ORR for treatment with brentuximab vedotin as 44% (17% CR) with a median duration of 16.6 months (Jacobsen, 2015).

Adverse Events and Warnings

The PI Label (2018) for brentuximab vedotin includes the following Black Box Warnings:

John Cunningham (JC) virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in individuals receiving brentuximab vedotin.

Additional warnings from the PI Label (2018) include the following:

Adverse Reactions:
The most common adverse reactions (greater than or equal to 20%) are neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, diarrhea, pyrexia, constipation, and vomiting.

Additional Warnings and Precautions:

Definitions

Antibodies: Proteins that are made by the immune system to help fight infection. Antibodies may also be cloned or developed in a laboratory (see monoclonal antibody).

Chemotherapy: Medical treatment of a disease, particularly cancer, with drugs or other chemicals.

CHOP: A regimen which includes cyclophosphamide, doxorubicin, vincristine, and prednisone.

Complete response (CR): The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured; also called a complete remission.

Hematopoietic stem cells: Primitive cells capable of replication and formation into mature blood cells in order to repopulate the bone marrow.

High-dose or myeloablative chemotherapy (HDC): The administration of cytotoxic agents using doses several times greater than the standard therapeutic dose.

Monoclonal antibody: A protein developed in the laboratory that can locate and bind to a specific target in the body.

Monotherapy: A single therapy; a single drug.

Partial response: A decrease in the size of a tumor or in the extent of cancer in the body, in response to treatment; also called a partial remission.

Primary refractory disease: Cancer that does not respond at the beginning of treatment; may also be called resistant disease.

Relapse: After a period of improvement, the signs and symptoms of cancer return.

References

Peer Reviewed Publications:

  1. Alderuccio JP, Desai A, Yepes MM, et al. Frontline brentuximab vedotin in breast implant-associated anaplastic large-cell lymphoma. Clin Case Rep. 2018; 6(4):634-637.
  2. Berger GK, McBride A, Lawson S, et al. Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review. Crit Rev Oncol Hematol. 2017; 109:42-50.
  3. Chen R, Palmer J, Martin P, et al. Results of a phase II trial of brentuximab vedotin as first line salvage therapy in relapsed/refractory HL prior to AHCT. Blood. 2014; 124; Abstract 501. Available at: http://www.bloodjournal.org/content/124/21/501?sso-checked=true. Accessed on December 18, 2018.
  4. Chen R, Palmer JM, Thomas SH, et al. Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2012; 119(26):6379-6381.
  5. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018; 378(4):331-344.
  6. Dada R, Zekri, Al Saadi R. Brentuximab vedotin in pretreated Hodgkin lymphoma patients: a systematic review and meta-analysis. Expert Opin Biol Ther. 2016; 16(6):739-745.
  7. Deutsch YE, Tadmor T, Podack ER, Rosenblatt JD. CD30: an important new target in hematologic malignancies. Leuk Lymphoma. 2011; 52(9):1641-1654.
  8. Duvic M, Tetzlaff MT, Gangar P, et al. Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. J Clin Oncol. 2015; 10; 33(32):3759-3765.
  9. Eichenauer DA, Plütschow A, Kreissl S et al. Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group. Lancet Oncol. 2017; 18(12):1680-1687.
  10. Enos TH, Feigenbaum LS, Wickless HW. Brentuximab vedotin in CD30+ primary cutaneous T-cell lymphomas: a review and analysis of existing data. Int J Dermatol. 2017; 56(12):1400-1405.
  11. Forero-Torres A, Holkova B, Goldschmidt J, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015; 126(26):2798-2804.
  12. Foyil KV, Bartlett NL. Brentuximab vedotin for the treatment of CD30+ lymphomas. Immunotherapy. 2011; 3(4):475-485.
  13. Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015; 125(8):1236-1243.
  14. Horwitz SM, Advani RH, Bartlett NL, et al. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014; 123(20):3095-3100.
  15. Horwitz S, O'Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2018. Dec 3. [Epub ahead of print].
  16. Jacobsen ED, Sharman JP, Oki Y, et al. Blood. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. 2015. 26; 125(9):1394-1402.
  17. Johnson L, O'Donoghue JM, McLean N, et al. Breast implant associated anaplastic large cell lymphoma: The UK experience. Recommendations on its management and implications for informed consent. Eur J Surg Oncol. 2017; 43(8):1393-1401.
  18. Kim YH, Tavallaee M, Sundram U, et al. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and sézary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol. 2015; 10; 33(32):3750-3758.
  19. LaCasce AS, Bociek RG, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018;132(1):40-48.
  20. Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 385(9980):1853-1862.
  21. Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017; 390(10094):555-566.
  22. Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012; 30(18):2190-2196.
  23. Pro B, Advani R, Brice P, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017; 130(25):2709-2717.
  24. Pro B, Advani R, Brice P. et al. Three-year survival results from an ongoing phase 2 study of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2013; 122: 1809.
  25. Sasse S, Rothe A, Goergen H, et al. Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma. Leuk Lymphoma. 2013; 54(10):2144-2148.
  26. Shustov A, Advani R, Brice P, et al. Durable remissions with SGN-35 (brentuximab vedotin): updated results of a phase 2 study in patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) [abstract]. Ann Oncol. 2011; 22(Supple 4): Abstract 125.
  27. Taverna JA, Yun S, Jonnadula J, et al. Role of maintenance therapy after high-dose chemotherapy and autologous hematopoietic cell transplantation in aggressive lymphomas: A systematic review. Biol Blood Marrow Transplant. 2016; 22(7):1182-1196.
  28. Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010; 363(19):1812-1821.
  29. Younes A, Connors JM, Park SI, et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013; 14(13):1348-1356.
  30. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012; 30(18):2183-2189.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Brentuximab Vedotin Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised March 9, 2015. Accessed on December 18, 2018.
  2. Brentuximab vedotin [Product Information]. Seattle Genetics, Inc., Bothell, WA; November 16, 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125388s099lbl.pdf. Accessed on December 18, 2018.
  3. Brentuximab vedotin. In: DrugPoints® System (electronic version). Truven Health Analytics. Greenwood Village, CO. Updated November 26, 2018. Available at: http://www.micromedexsolutions.com. Accessed on December 18, 2018.
  4. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium® (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on December 18, 2018.
  5. NCCN Clinical Practice Guidelines in Oncology®. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on December 18, 2018.
    • B-Cell Lymphomas. V.1.2019. Updated November 30, 2018.
    • Hodgkin Lymphoma. V.3.2018. Updated April 16, 2018.
    • Primary Cutaneous Lymphomas. V.2.2019. Updated December 17, 2018.
    • T-Cell Lymphomas. V.2.2019. Updated December 17, 2018.
Websites for Additional Information
  1. American Cancer Society (ACS). Available at: http://www.cancer.org/cancer/index. Accessed on December 18, 2018.
  2. American College of Nuclear Medicine (ACNM).  Deuville Criteria. 2014. Available at: http://www.snmmi.org/ACNM/Residents/Content.aspx?ItemNumber=12279. Accessed on December 18, 2018.
  3. National Cancer Institute (NCI). Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. Reviewed on March 01, 2018. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant. Accessed on December 18, 2018.
  4. National Cancer Institute (NCI). PDQ® Adult Hodgkin Lymphoma Treatment. Last modified August 15, 2018. Available at: http://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq. Accessed on December 18, 2018.
  5. National Cancer Institute (NCI). PDQ® Adult Non-Hodgkin Lymphoma Treatment. Last modified October 4, 2018. Available at: http://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq. Accessed on December 18, 2018.
  6. National Cancer Institute (NCI). PDQ® Mycosis Fungoides and the Sézary Syndrome. Last modified May 04, 2018. Available at: http://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq. Accessed on December 18, 2018.
  7. National Institutes of Health (NIH). ClinicalTrials.gov. Available at: http://clinicaltrials.gov/. Accessed on December 18, 2018.
Index

SGN-35
Anti-CD30

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised

01/24/2019

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

01/16/2019

Hematology/Oncology Subcommittee Review. Updated MN indications for untreated HL to specify regimen. Expanded MN indications to include combination therapy with bendaumstine for relapsed/refractory HL and combination therapy with cyclophosphamide, doxorubicin, and prednisone for previously untreated CD30+ PTCL. Updated Coding, Discussion/General Information and Reference Sections.

New

07/26/2018

MPTAC review.

New

07/18/2018

Hematology/Oncology Subcommittee Review. Initial document development. Moved content of DRUG.00047 Brentuximab vedotin (Adcetris®) to new clinical utilization management guideline document with the same title.