ASH Clinical News ACN_4.2_FULL_ISSUE | Page 5

National Comprehensive Cancer Network 23rd Annual Conference

March 22 – 24 , 2018 Orlando , FL The annual conference brings together oncology professionals to discuss the data upon which the NCCN Guidelines ® are based , as well as the latest in oncology care .

American Association for Cancer Research Annual Meeting

April 14 – 18 , 2018 Chicago , IL The annual meeting , for which the theme is “ Driving Innovative Cancer Science to Patient Care ,” highlights cancer science and medicine from international institutions .

Highlights of ASH ® Asia - Pacific

March 9 – 10 , 2018 Bali , Indonesia

Bali , Indonesia

Highlights of ASH ® Latin America

April 27 – 28 , 2018 Rio de Janeiro , Brazil

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Of the 131 enrolled patients , 128 ( 66 brentuximab vedotin , 62 physician ’ s choice ) received at least one dose of study treatment . The median number of treatment cycles in the ADCETRIS-treatment arm was 12 ( range , 1-16 ) compared to 3 ( range , 1-16 ) and 6 ( range , 1-16 ) in the methotrexate and bexarotene arms , respectively . Twenty-four ( 24 ) patients ( 36 %) in the ADCETRIS-treatment arm received 16 cycles compared to 5 patients ( 8 %) in the physician ’ s choice arm .

Adverse reactions that led to dose delays in more than 5 % of ADCETRIS-treated patients were peripheral sensory neuropathy ( 15 %) and neutropenia ( 6 %). Adverse reactions led to treatment discontinuation in 24 % of ADCETRIS-treated patients . The most common adverse reaction that led to treatment discontinuation was peripheral neuropathy ( 12 %). Serious adverse reactions were reported in 29 % of ADCETRIStreated patients . The most common serious adverse reactions were cellulitis ( 3 %) and pyrexia ( 3 %).

Table 7 : Adverse Reactions Reported in ≥10 % ADCETRIS-treated Patients with pcALCL or CD30-expressing MF ( Study 4 : ALCANZA )

Adverse Reaction

Any Grade

ADCETRIS n = 66 % of patients

Grade 3

Grade 4

Physician ’ s Choice † n = 62 % of patients

Any Grade

Grade 3

Grade 4

Neutropenia * 21 3 2 24 5 -

Diarrhea 29 3 - 6 - -

* Derived from laboratory values and adverse reaction data . † Physician ’ s choice of either methotrexate or bexarotene . Events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI CTCAE ) Version 4.03 .

Additional Important Adverse Reactions Infusion reactions

In studies of ADCETRIS as monotherapy ( Studies 1-4 ), 13 % of ADCETRIS-treated patients experienced infusion-related reactions . The most common adverse reactions in Studies 1-4 ( ≥3 % in any study ) associated with infusion-related reactions were chills ( 4 %), nausea ( 3-4 %), dyspnea ( 2-3 %), pruritus ( 2-5 %), pyrexia ( 2 %), and cough ( 2 %). Grade 3 events were reported in 5 of the 51 ADCETRIS-treated patients who experienced infusion-related reactions .

Pulmonary toxicity

In a trial in patients with cHL that studied ADCETRIS with bleomycin as part of a combination regimen , the rate of non-infectious pulmonary toxicity was higher than the historical incidence reported with ABVD ( adriamycin , bleomycin , vinblastine , dacarbazine ). Patients typically reported cough and dyspnea . Interstitial infiltration and / or inflammation were observed on radiographs and computed tomographic imaging of the chest . Most patients responded to corticosteroids . The concomitant use of ADCETRIS with bleomycin is contraindicated .

Cases of pulmonary toxicity have also been reported in patients receiving ADCETRIS . In Study 3 ( AETHERA ), pulmonary toxicity was reported in 8 patients ( 5 %) in the ADCETRIS-treated arm and 5 patients ( 3 %) in the placebo arm .

6.2 Post Marketing Experience

The following adverse reactions have been identified during post-approval use of ADCETRIS . Because these reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure .

Blood and lymphatic system disorders : febrile neutropenia .

Gastrointestinal disorders : acute pancreatitis and gastrointestinal complications ( including fatal outcomes ).

Hepatobiliary disorders : hepatotoxicity . Infections : PML , serious infections and opportunistic infections . Metabolism and nutrition disorders : hyperglycemia .

Respiratory , thoracic and mediastinal disorders : noninfectious pulmonary toxicity including pneumonitis , interstitial lung disease , and ARDS ( some with fatal outcomes ).

Skin and subcutaneous tissue disorders : Toxic epidermal necrolysis , including fatal outcomes .

6.3 Immunogenicity

As with all therapeutic proteins , there is potential for immunogenicity . The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay . Additionally , the observed incidence of antibody ( including neutralizing antibody ) positivity in an assay may be influenced by several factors including assay methodology , sample handling , timing of sample collection , concomitant medications , and underlying disease . For these reasons , comparison of the incidence of antibodies to ADCETRIS in the studies described below with the incidence of antibodies in other studies or to other products may be misleading .

Patients with cHL and systemic anaplastic large cell lymphoma ( sALCL ) in Studies 1 and 2 were tested for antibodies to brentuximab vedotin every 3 weeks using a sensitive electrochemiluminescent immunoassay . Approximately 7 % of patients in these trials developed persistently positive antibodies ( positive test at more than 2 timepoints ) and 30 % developed transiently positive antibodies ( positive in 1 or 2 post-baseline timepoints ). The anti-brentuximab antibodies were directed against the antibody component of brentuximab vedotin in all patients with transiently or persistently positive antibodies . Two of the patients ( 1 %) with persistently positive antibodies experienced adverse reactions consistent with infusion reactions that led to discontinuation of treatment . Overall , a higher incidence of infusion related reactions was observed in patients who developed persistently positive antibodies .

A total of 58 patient samples that were either transiently or persistently positive for anti-brentuximab vedotin antibodies were tested for the presence of neutralizing antibodies . Sixty-two percent ( 62 %) of these patients had at least one sample that was positive for the presence of neutralizing antibodies . The effect of anti-brentuximab vedotin antibodies on safety and efficacy is not known .

7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on ADCETRIS

CYP3A4 Inhibitors : Co-administration of ADCETRIS with ketoconazole , a potent CYP3A4 inhibitor , increased exposure to MMAE , which may increase the risk of adverse reaction . Closely monitor adverse reactions when ADCETRIS is given concomitantly with strong CYP3A4 inhibitors .

P-gp Inhibitors : Co-administration of ADCETRIS with P-gp inhibitors may increase exposure to MMAE . Closely monitor adverse reactions when ADCETRIS is given concomitantly with P-gp inhibitors .