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Lymphoma brentuximab vedotin

Patients with lymphoma should be considered for inclusion into clinical trials. Link to ALLG website, ANZCTR website and Lymphoma Australia website.

Some indications in this protocol are based on limited evidence; please refer to the individual evidence sections for more information.

The anticancer drug(s) in this protocol may have been included in the ADDIKD guideline. Dose recommendations in kidney dysfunction have yet to be updated to align with the ADDIKD guideline. Recommendations will be updated once the individual protocol has been evaluated by the reference committee. For further information refer to the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) calculator.

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The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 16

Day 1
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Brentuximab vedotin 1.8 mg/kg (IV infusion) (Cap dose at 180 mg) in 150 mL sodium chloride 0.9% over 30 minutes
Frequency:
21 days 
Cycles:
16 or until disease progression or unacceptable toxicity

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 16

Day 1
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Brentuximab vedotin 1.8 mg/kg (IV infusion) (Cap dose at 180 mg) in 150 mL sodium chloride 0.9% over 30 minutes
Frequency:
21 days 
Cycles:
16 or until disease progression or unacceptable toxicity
  • Relapsed or refractory CD30+ Hodgkin lymphoma either following autologous stem cell transplant (ASCT) OR following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option.
  • Patients with CD30+ Hodgkin lymphoma at higher risk of relapse or progression following ASCT.
  • Relapsed or refractory CD30+ systemic anaplastic large cell lymphoma in patients who have undergone appropriate prior front-line curative chemotherapy.
  • Relapsed or refractory CD30+ cutaneous T-cell lymphoma (including mycoses fungoides, Sezary syndrome or primary cutaneous anaplastic large cell lymphoma).
Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Hypersensitivity/infusion related reaction

High risk with brentuximab vedotin.

Patients who have experienced a prior infusion-related reaction should be given premedication (e.g. paracetamol, an antihistamine and a corticosteroid) for subsequent infusions.
Emetogenicity LOW

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Progressive multifocal leukoencephalopathy

Reactivation of the John Cunningham virus (JCV) in patients who have received brentuximab vedotin after receiving multiple chemotherapy regimens previously has resulted in progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal opportunistic viral infection of the brain. Patients must be monitored for any new or worsening neurological symptoms. Brentuximab vedotin treatment may have to be withheld if PML is suspected or discontinued if diagnosis is confirmed.

Read more about progressive multifocal leukoencephalopathy and the Therapeutic Goods Administration Medicines Safety update on progressive multifocal leukoencephalopathy from the Australian Government, Department of Health.
Pancreatitis

Pancreatitis is uncommon but has been reported. Unexplained abdominal pain should be promptly investigated to include measurement of serum amylase and lipase.
Pulmonary toxicity

Brentuximab vedotin has been associated with pulmonary toxicity. Patients should be monitored for pulmonary symptoms (e.g. cough, dyspnoea). If new or worsening pulmonary symptoms occur, a prompt diagnostic evaluation should be performed and patients should be treated appropriately.

Read more about pulmonary toxicity associated with anti-cancer drugs.
Peripheral neuropathy

Assess prior to each treatment. If a patient experiences grade 2 or greater peripheral neuropathy, a dose reduction, delay, or omission of treatment may be required; review by medical officer before commencing treatment.

Read more about peripheral neuropathy

Link to chemotherapy-induced peripheral neuropathy screening tool
Tumour lysis risk

Patients are at high risk of developing tumour lysis syndrome, prophylaxis is recommended.

Read more about the prevention and management of tumour lysis syndrome.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis

­

Read more about prophylaxis of pneumocystis jiroveci (carinii) in cancer patients
Antifungal prophylaxis ­

Read more about antifungal prophylaxis drugs and doses.
Antiviral prophylaxis

­

Read more about antiviral prophylaxis drugs and doses
Growth factor support

G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.  

Access the PBS website
Irradiated blood components

The use of irradiated of blood components is recommended for patients receiving this treatment.

Read more about the indications for the use of irradiated blood components
Blood tests

FBC, EUC, LFTs and LDH at baseline, and prior to each cycle and as clinically indicated.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of foetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the effect of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
The dose recommendations in kidney dysfunction (i.e.renal impairment) displayed may not reflect those in the ADDIKD guideline and have been included for historical reference only. Recommendations will be updated once the individual protocol has been evaluated by the reference committee, with this version of the protocol then being archived. Clinicians are expected to refer to the ADDIKD guideline prior to prescribing in kidney dysfunction.
International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
Haematological toxicity
ANC x 109/L (pre-treatment blood test)
less than 1.0 Delay treatment until recovery and resume brentuximab vedotin at the same dose (and consider adding G-CSF for subsequent cycles)
Renal impairment
Creatinine clearance (mL/min)
less than 30 Patients with active disease and no other treatment options, consider use with caution after evaluating benefit-risk at a starting dose of 1.2 mg/kg
Hepatic impairment
Hepatic dysfunction
Use with caution in patients with hepatic impairment, due to potential increased exposure to MMAE (conjugated anti-microtubule agent) and increased toxicity.
Mild (Child-Pugh A) Recommend reducing starting dose to 1.2 mg/kg
Moderate (Child-Pugh B) to Severe (Child-Pugh C) Patients with active disease and no other treatment options, consider use with caution after evaluating benefit-risk at a starting dose of 1.2 mg/kg
Peripheral neuropathy
Grade 2 or Grade 3 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose of brentuximab vedotin to 1.2 mg/kg for subsequent cycles.
Grade 4 Omit brentuximab vedotin

Drug interactions in eviQ protocols are under review and being updated to align with current literature. Further site-wide updates and changes will occur in due course. References & Disclaimer

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources:  

Brentuximab vedotin
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, ciclosporin, grapefruit juice etc.) Increased toxicity of MMAE (conjugated anti-microtubule agent) possible due to reduced clearance Avoid combination or monitor for MMAE toxicity and reduce the dose appropriately
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John's wort etc.) Reduced efficacy of MMAE possible due to increased clearance Avoid combination or monitor for decreased clinical response to MMAE
Bleomycin May have additive effect with brentuximab vedotin and is associated with pulmonary toxicity Avoid combination as it is contraindicated
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA website for further information.

Day 1

Approximate treatment time: 60 minutes

General patient assessment prior to each day of treatment.

Peripheral neuropathy assessment tool

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

  • weigh patient on each visit 

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Brentuximab vedotin

Administer brentuximab vedotin (irritant):
  • via IV infusion over 30 minutes
  • flush with 50 mL of sodium chloride 0.9%
  • Patients should be closely monitored during and after the infusion. If a patient experiences an infusion-related reaction, stop the infusion immediately. Review by medical officer. Give any further doses with close monitoring. Premedication with paracetamol, an antihistamine and a corticosteroid should be considered for further doses for patients who have experienced a prior infusion related reaction.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions until 7 days after completion of drug(s)

Discharge information

Antiemetics
  • Antiemetics as prescribed.
Growth factor support
  • Arrangements for administration if prescribed.
Prophylaxis medications
  • Prophylaxis medications (if prescribed) i.e. tumour lysis prophylaxis, PJP prophylaxis, antifungals, antivirals.
Patient information
  • Ensure patient receives patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Abdominal pain

Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation.
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia
Constipation
Diarrhoea

Read more about treatment induced diarrhoea
Dizziness

Feeling faint or lightheaded, weak or unsteady. Advise patients to stand up slowly from sitting down or lying down positions and increase fluid intake if dehydrated.
Dyspnoea
Fatigue

Read more about fatigue
Fever
Hyperglycaemia

High blood sugar, an excess of glucose in the blood stream.
Hepatotoxicity

Anti-cancer drugs administered either alone or in combination with other drugs and/or radiation may cause direct or indirect hepatotoxicity. Hepatic dysfunction can alter the metabolism of some drugs resulting in systemic toxicity.
Peripheral neuropathy

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet.  It is associated with several classes of anti-cancer drugs. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Read more about peripheral neuropathy
Respiratory tract infection
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash

Late (onset weeks to months)
Alopecia

Hair loss may occur from all parts of the body. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Progressive multifocal leukoencephalopathy (PML)

A rare opportunistic viral infection of the brain, usually leading to death or severe disability, can occur with monoclonal antibodies (e.g. rituximab, obinutuzumab, ofatumumab, brentuximab vedotin) and other targeted therapies (e.g. ibrutinib, ruxolitinib, idelalisib). Onset may occur up to months after the final dose.  

Read more about progressive multifocal leukoencephalopathy (PML)
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs

Brentuximab vedotin is an anti-CD30 antibody that is conjugated to an anti-microtubule agent, monomethyl aurostatin E (MMAE). This drug enables selective delivery of MMAE to CD30 expressing cells to cause apoptosis and cell cycle arrest.

The primary evidence supporting the use of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma is provided by the pivotal single-arm multicentre phase II trial (trial SG035-0003). This study enrolled 102 patients who had CD30-positive Hodgkin lymphoma who relapsed post autologous stem cell transplant (ASCT), 71% of whom had primary refractory disease. This was initially reported in 2012r with long term data subsequently reported in 2016.r All patients received brentuximab vedotin (1.8 mg/kg IV every 3 weeks for up to 16 doses). 

Source Study & Year Published Supports Use Is the dose and regimen consistent with the protocol? Comments
Phase II trials Younes et al. 2012 Yes Yes - 
Phase II trials Chen et al. 2016 Yes Yes -
Guidelines Date published/revised Supports Use Is the dose and regimen consistent with the protocol? Comments
NCCN  v.2 2015 Yes N/A - 
BCCA  Jun 2014 Yes Yes - 
CCO Mar 2015 Yes  Yes  -

Efficacy

As per the long term follow-up datar, at a median follow-up of 35.1 months, the median OS and PFS were 40.5 and 9.3 months respectively. The estimated 5-year OS and PFS rates were 41% and 22%, respectively.

34/102 (33%) achieved CR on study.

In those achieving CR, median response duration was not reached, while the 5 year OS was 64% and PFS 52%. Of the 13/34 patients achieving CR who then remained in CR at study close, 4 had undergone allogeneic transplant, while 9 had received no further therapy. A number of patients who relapsed after discontinuing brentuximab vedotin in remission were rechallenged with brentuximab vedotin.r Of 21 retreated patients, there was a 60% second objective response rate (CR 30%). 

Note that there is evidence that some patients can respond to retreatment with brentuximab after having previously discontinued brentuximab therapy.r

  

© Journal of Clinical Oncology 2012

 

© Blood 2016

Toxicity

The most clinically relevant adverse event was peripheral neuropathy (PN) in 42% of patients, the majority (36%) of which was grade 1 or 2. Neuropathy typically developed after prolonged drug exposure (median onset of grade 2 and grade 3 PN was 27.3 weeks and 38.0 weeks, respectively). The majority of PN (80%) was reversible upon dose reduction/discontinuation. Other common toxicities are as outlined in the table below. 55% of patients experienced grade 3 adverse events. Twenty of 102 patients had adverse events that led to treatment discontinuation. No drug-related deaths occurred.r

© Journal of Clinical Oncology 2012

The AETHERA study investigated the role of brentuximab vedotin (BV) administered as consolidation following autologous stem cell transplantation in patients considered at high risk of relapse or progression.r In this randomised, double-blind, placebo-controlled Phase III trial, patients were eligible if they had failed to achieve a complete response to front-line therapy, relapsed following an initial remission duration of less than 12 months, or had extranodal disease at the time of commencement of pre-transplant salvage therapy. 165 patients were randomised to receive brentuximab vedotin, with 164 patients in the placebo arm. Brentuximab was administered in the same dosing schedule as the SG035-0003 study above.

Efficacy

After a median of 30 months follow-up, progression-free survival (PFS) was significantly improved in patients in the BV arm [HR=0.57, 95% CI 0.40-0.81, p=0.0013]. Median PFS was 42.9 months in the BV arm versus 24.1 months in the placebo group. Overall survival was not seen to be different between the two arms. Benefit appeared to be maintained across most subgroups analysed.

Progression free and overall survival analyses​ r

© Lancet 2015

A subsequent brief report was published updating outcomes to a median follow-up of 5 years.r Longer PFS continued to be demonstrated in the BV arm (Median not reached versus 15.8 months for placebo). Significantly fewer BV treated patients required subsequent anti-lymphoma treatment (54% v 32%, p<0.001), with 87% of patients requiring treatment in the placebo arm receiving BV at disease progression.

Toxicity

32% of patients in the BV arm required dose modifications versus 3% in the placebo arm. Peripheral neuropathy was again the most commonly reported adverse event (AE), with 56% of patients experiencing any grade, and 10% ≥ Grade 3. Neutropenia was the most commonly reported severe AE, with 29% experiencing ≥ Grade 3 toxicity (35% any grade). r

© Biol Blood Marrow Transplant 2018

In the 5 year follow-up, 90% of patients who experience peripheral neuropathy reported resolution or improvement, with 73% having complete resolution. Median time to resolution was 37.6 weeks. There was no difference in incidence of secondary malignancies between the two groups.r

Brentuximab vedotin is an anti-CD30 antibody that is conjugated to an anti-microtubule agent, monomethyl aurostatin E (MMAE). This drug enables selective delivery of MMAE to CD30 expressing cells to cause apoptosis and cell cycle arrest.

The primary evidence supporting the use of brentuximab vedotin in this setting is a pivotal phase 2 study of 58 patients with relapsed/refractory anaplastic large cell lymphoma (ALCL). This study was initially reported in 2012r and updated in 2017r. The regimen was identical to that for Hodgkin lymphoma as above.

Source Study & Year Published Supports Use Is the dose and regimen consistent with the protocol? Comments
Phase II trials Pro et al. 2012 Yes Yes - 
Phase II trials Pro et al. 2017 Yes Yes -
Guidelines Date published/revised Supports Use Is the dose and regimen consistent with the protocol? Comments
NCCN T-Cell lymphoma 2018 v.4 Yes Yes - 
BCCA  Jun 2014 Yes Yes - 
CCO Mar 2015 Yes  Yes  -

Efficacy

Of 58 patients enrolled, 16/58 (28%) were ALK+ve, while 42/58 (72%) were ALK-ve. 36/58 (62%) were primary refractory to frontline therapy, including 13 (22%) who had no previously demonstrated response. At a median follow-up of 71.4 months, the estimated 5-yr overall survival (OS) and progression-free survival (PFS) were 60% and 39%, respectively. The duration of median OS was not reached, while median PFS was 20 months.r

16 of 38 patients achieving CR (42%) underwent consolidative stem cell transplant. 11 of these patients (69%) remained alive and progression free. Outcomes were similar between autologous and allogeneic transplants (PFS 75% versus 63%, respectively). However, of the 8 allogeneic transplants, 6 had previously undergone autologous transplantation. Of the 22 CR patients who did not receive SCT (58%), 12 (54%) were alive without progressive disease.r

Note that, as with Hodgkin lymphoma, there is evidence that some patients can respond to re-treatment with brentuximab after having previously discontinued brentuximab therapy.r

© Blood 2017

 

© Blood 2017

 

© Blood 2017

Toxicity

Toxicity was similar to that seen with Hodgkin lymphoma as above.

© Journal of Clinical Oncology 2012

Brentuximab vedotin is an anti-CD30 antibody that is conjugated to an anti-microtubule agent, monomethyl aurostatin E (MMAE). This drug enables selective delivery of MMAE to CD30 expressing cells to cause apoptosis and cell cycle arrest.

The evidence supporting this protocol is provided by a phase III multicentre international randomised trial involving 131 patients comparing Brentuximab with physician’s choice of therapy in patients with relapsed refractory CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma.r

Between 2012 and 2015, 66 patients were randomised to receive brentuximab vedotin (BV) 1.8mg/kg every 3 weeks for up to 16 cycles, and 65 patients were randomised to receive physician’s choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary end point was the proportion obtaining an objective global response of at least 4 months.

Efficacy

After a median follow up of 22.9 months, the primary endpoint (objective global response of at least 4 months) was achieved in 56.3% of the BV arm versus 12.5% in the best supportive arm, which is an improvement of 43.8% (95% CI 29.1–58.4; p<0.0001).

© Lancet 2017

Median progression-free survival (PFS) (EMA criteria) was 16.7 months versus 3.5 months (HR 0.270, 95% CI 0.169–0.430; p<0.0001; adjusted p<0.0001). Median duration of response for the 43 responders to BV was 15.1 months (95% CI 9.7–25.5) versus 18.3 months (3.5–18.4) for the 13 responders to physician’s choice treatment.

Patient-reported symptoms (Skindex-29), showed significantly greater symptom reduction in the brentuximab vedotin group, compared with the physician’s choice group, with a mean maximum reduction of –27.96 (SD 26.877) versus –8.62 (17.013; p<0.0001).

A final analysis has been presented in abstract form at ICML15.r At a median follow-up of 45.9 months, the benefit in median PFS was maintained (16.7 v 3.5 months, p<0.001). Similar numbers of patients had received subsequent therapy in each group (78% v 75%), but median time to next therapy remained significantly longer in the BV treated group (14.2 v 5.6 months, p<0.001).

Toxicity

The median duration of treatment was 269 days of BV versus 114 days of bexarotene and 77 days of methotrexate. The most frequent reasons for treatment discontinuation were completion of 16 cycles in the brentuximab vedotin group (23 [35%] of 66 patients). Adverse events led to discontinuation in 16 (24%) patients in the BV group versus five (8%) in the physician’s choice group.

Peripheral neuropathy was identified in 44 (67%) of 66 patients in the brentuximab vedotin group (n=17 grade 1, n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician’s choice group (n=1 grade 1, n=3 grade 2). This led to 9/66 patients in the BV arm discontinuing BV therapy (compared to none discontinuing for this indication in the physicians choice arm).

In the updated analysis, 86% of patients with peripheral neuropathy had resolution or improvement, with no patients having persistent neuropathy ≥ Grade 3.r

© Lancet 2017

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Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

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Version 5

Date Summary of changes
27/03/2020

Protocol reviewed by Haematology Reference Committee:

  • New indications added to include high risk Hodgkin lymphoma post ASCT
  • New evidence added for high risk Hodgkin lymphoma post ASCT
  • New evidence added for cutaneous T-cell lymphoma
  • Version number changed to v.5
22/10/2021 Protocol reviewed by Haematology Reference Committee. Clinical information & side effects updated. Review in 2 years.
31/08/2022 Brentuximab vedotin extravasation category updated to align with extravasation clinical resources update.

Version 4

Date Summary of changes
13/09/2019

Protocol reviewed at Haematology Reference Committee meeting:

  • Reformatted as per eviQ multi-indication protocol standard
  • New indications updated to include Cutaneous T-cell lymphoma
  • Hepatic dose modifications clarified
  • New evidence added for Cutaneous T-cell lymphoma
  • Peripheral neuropathy checklist added in Administration section
  • Version number changed to v.4
10/10/2019 Clinical information updated with PBS expanded indications for G-CSF. 

Version 3

Date Summary of changes
26/02/2016 Approved and published on eviQ
31/05/2017

Transferred to new eviQ website. Version number change to v.2.
25/05/2018

Protocol reviewed at Haematology Reference Committee meeting:

  • Title changed from Hodgkin lymphoma to Lymphoma
  • New indications updated to include anaplastic large cell lymphoma.
  • Hepatic dose modifications clarified
  • Existing evidence for Hodgkin lymphoma updated and new evidence added for anaplastic large cell lymphoma.
  • Version number changed to v.3.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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https://www.eviq.org.au/p/1665

31 Mar 2023