ダラザレックス点滴静注 100 mg ダラザレックス点滴静注 400 mg に関する資料本資料に記載された情報に係る権利及び内容についての責任はヤンセンファーマ株式会社に帰属するものであり当該情報を本薬剤の適正使用以外の営利目的に使用することはできませんヤンセンファーマ株式会社

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ダラザレックス点滴静注 100 mg

ダラザレックス点滴静注 400 mg

に関する資料

ヤンセンファーマ株式会社

本資料に記載された情報に係る権利及び内容についての責任は、ヤンセンファーマ株式会社に帰属するものであり、当該情報を本薬剤の適正使用以外の営利目的に使用することはできません。

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ࢲࣛࢶ࣒࣐ࣈ 1.5 ㉳ཎཪࡣⓎぢࡢ⤒⦋ཬࡧ㛤Ⓨࡢ⤒⦋

┠ḟ

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␎ྕ୍ぴ⾲

␎ྕཪࡣ␎⛠ ྡ⛠ཬࡧෆᐜ DVd Daratumumab-bortezomib-dexamethasone 㸦ࢲࣛࢶ࣒࣐ࣈ-࣎ࣝࢸࢰ࣑ࣈ-ࢹ࢟ࢧ࣓ࢱࢰࣥ㸧 MM multiple myeloma㸦ከⓎᛶ㦵㧊⭘㸧 Rd lenalidomide-dexamethasone㸦ࣞࢼࣜࢻ࣑ࢻ-ࢹ࢟ࢧ࣓ࢱࢰࣥ㸧 Vd bortezomib-dexamethasone㸦࣎ࣝࢸࢰ࣑ࣈ-ࢹ࢟ࢧ࣓ࢱࢰࣥ㸧

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1.5 ㉳ཎཪࡣⓎぢࡢ⤒⦋ཬࡧ㛤Ⓨࡢ⤒⦋

ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧㸦௨ୗᮏ๣㸧ࡣ㸪Genmab ♫࡟ࡼࡾ๰〇ࡉࢀࡓ᏶඲ࣄࢺᆺච␿ ࢢࣟࣈࣜࣥG1țࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛㸪ከⓎᛶ㦵㧊⭘㸦௨ୗMM㸧ࢆྵࡴ㐀⾑ჾ⭘⒆ࡢ⭘⒆⣽⬊ ⾲㠃࡟Ⓨ⌧ࡍࡿCD38 ᢠཎ࡟ᑐࡋ࡚≉␗ⓗ࡟⤖ྜࡍࡿࡇ࡜࡟ࡼࡾ㸪ᢠ⭘⒆ຠᯝࢆⓎ᥹ࡍࡿ⸆๣࡛ ࠶ࡿ࠙2.5.1.1ࠚࠋ ᮏ๣ࡣ㸪⡿ᅜ࡛ࡣ2015 ᖺ11 ᭶࡟ࠕࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࢆྵࡴ3 ࣞࢪ࣓ࣥ௨ ୖࡢ๓἞⒪Ṕࢆ᭷ࡍࡿ㸪ཪࡣࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࡢ୧๣࡟㞴἞ᛶࡢከⓎᛶ㦵㧊 ⭘ࠖࢆຠ⬟࣭ຠᯝ࡜ࡋ࡚㎿㏿ᢎㄆ㸦Accelerated approval㸧ࢆྲྀᚓࡋ㸪Ḣᕞ࡛ࡣ2016 ᖺ5 ᭶࡟ࠕࣉ ࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࢆྵࡴ๓἞⒪Ṕࢆ᭷ࡋ㸪┤㏆ࡢ἞⒪࡟ᑐࡋ࡚⑌ᝈ㐍⾜ࢆ♧ࡋ ࡓ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ࠖࢆຠ⬟࣭ຠᯝ࡜ࡋ࡚᮲௳௜ࡁᢎㄆ㸦Conditional approval㸧ࢆ ྲྀᚓࡋࡓࠋࡲࡓ㸪෌Ⓨཪࡣ㞴἞ᛶࡢMMᝈ⪅ࢆᑐ㇟࡟㸪ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ㸦௨ୗ Rd㸧࡬ࡢୖ஌ࡏຠᯝࢆ᳨ウࡍࡿ➨III ┦ᅜ㝿ඹྠヨ㦂ࡢ54767414MMY3003㸦௨ୗMMY3003㸧ヨ㦂㸪࣎ࣝࢸࢰ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ㸦௨ୗVd㸧࡬ࡢୖ஌ࡏຠᯝࢆ᳨ウࡍࡿᾏእ➨III ┦ヨ㦂ࡢ 54767414MMY3004ヨ㦂ࢆᐇ᪋ࡋ㸪ᮏ๣ࢆྵࡴే⏝⩌ࡢඃ㉺ᛶࡀ♧ࡉࢀ㸪Ᏻ඲ᛶཬࡧᚸᐜᛶࡀ☜ ㄆࡉࢀࡓࡇ࡜࠿ࡽ㸪⡿ᅜ࡛ࡣ2016ᖺ11᭶㸪Ḣᕞ࡛ࡣ2017ᖺ4᭶࡟ࠕ1ᅇ௨ୖࡢ๓἞⒪Ṕࢆ᭷ࡍࡿከ Ⓨᛶ㦵㧊⭘ࠖࢆຠ⬟࣭ຠᯝ࡜ࡋ࡚ᢎㄆࢆྲྀᚓࡋࡓࠋ ᅜෆ࡛ࡣ㸪෌Ⓨཪࡣ㞴἞ᛶࡢMMᝈ⪅ࢆᑐ㇟࡜ࡋࡓ༢๣⒪ἲࡢ➨I ┦ヨ㦂㸦54767414MMY1002 ヨ㦂㸧㸪ᮏ๣࡜Vd ࡜ࡢే⏝⒪ἲ㸦௨ୗDVd㸧ࡢ➨Ib ┦ヨ㦂㸦54767414MMY1005ヨ㦂㸧ࢆᐇ᪋ࡋ㸪 ᪥ᮏே࡟࠾ࡅࡿᮏ๣༢๣⒪ἲཬࡧDVd ⒪ἲࡢᚸᐜᛶཬࡧᏳ඲ᛶࡀ☜ㄆࡉࢀ㸪᭷ຠᛶࡣ᪥ᮏே࡛ࡶ ᮇᚅ࡛ࡁࡿ࡜⪃࠼ࡽࢀࡓࠋ᭦࡟㸪ୖ㏙ࡢ෌Ⓨཪࡣ㞴἞ᛶࡢMMᝈ⪅ࢆᑐ㇟࡜ࡋࡓRd ࡬ࡢୖ஌ࡏຠ ᯝࢆ᳨ウࡋࡓMMY3003 ヨ㦂࡟ཧຍࡋࡓ⤖ᯝ㸪඲య㞟ᅋࡢ⤖ᯝ࡜ྠᵝ࡟᪥ᮏே࡟࠾࠸࡚ࡶ⮫ᗋⓗ ࣋ࢿࣇ࢕ࢵࢺࡀᚓࡽࢀࡿ࡜⪃࠼ࡽࢀࡓࠋ ௨ୖࡼࡾ㸪ᮏ๣ࡢ༢๣⒪ἲཬࡧే⏝⒪ἲࡣ㸪᪥ᮏேࡢ෌Ⓨཪࡣ㞴἞ᛶࡢMMᝈ⪅࡟ᑐࡋ࡚ࡶ᭷ ⏝࡞἞⒪㑅ᢥ⫥࡟࡞ࡿ࡜⪃࠼㸪ࠕ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ࠖࢆ⏦ㄳຠ⬟࣭ຠᯝ࡜ࡋࡓ〇㐀㈍኎ᢎㄆ⏦ㄳࢆ⾜࠺ࡇ࡜࡜ࡋࡓ࠙2.5.1.4, 2.5.1.5ࠚࠋ ㉳ཎཪࡣⓎぢࡢ⤒⦋ཬࡧ㛤Ⓨࡢ⤒⦋࡟ࡘ࠸࡚ࡣ㸪ᖹᡂ13 ᖺ6 ᭶21 ᪥௜་⸆ᑂⓎ➨899 ྕ་⸆ᒁ ᑂᰝ⟶⌮ㄢ㛗㏻▱ࠕ᪂་⸆ရࡢ〇㐀ཪࡣ㍺ධࡢᢎㄆ⏦ㄳ࡟㝿ࡋᢎㄆ⏦ㄳ᭩࡟ῧ௜ࡍ࡭ࡁ㈨ᩱࡢస ᡂせ㡿࡟ࡘ࠸࡚ࠖࡢู⣬2 ࡢ5㸦1㸧㡯ࡢグ㏙ࢆࡶ࡜࡟㸪ᙜヱෆᐜࢆ୺࡟➨2 㒊㸦5㸧࡟グ㍕ࡋࡓ 㸦⾲1.5-1㸧ࠋࡲࡓ㸪ᮏ⏦ㄳ࡟㛵ࡍࡿရ㉁࡟㛵ࡍࡿヨ㦂ཬࡧ㠀⮫ᗋヨ㦂㸪⮫ᗋヨ㦂ࡢ㛤Ⓨ⤒⦋ࢆ㸪 ࡑࢀࡒࢀ⾲1.5-2ཬࡧ⾲1.5-3 ࡟♧ࡍࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.5 ㉳ཎཪࡣⓎぢࡢ⤒⦋ཬࡧ㛤Ⓨࡢ⤒⦋ ⾲ 1.5-1 CTD1.5 㡯ࡢෆᐜࡢグ㍕ሙᡤ CTD 1.5 㡯ࡢෆᐜ CTD ➨ 2 㒊ࡢグ㍕ሙᡤ ㉳ཎཪࡣⓎぢࡢ⤒⦋ 2.5.1 〇ရ㛤Ⓨࡢ᰿ᣐ MM ࡢ⑓ែཬࡧ␿Ꮫ 2.5.1.2 ⏦ㄳຠ⬟࣭ຠᯝࡢ⮫ᗋⓗཪࡣ⑓ែ⏕⌮Ꮫⓗഃ㠃 MM ࡢ἞⒪ 2.5.1.3 ከⓎᛶ㦵㧊⭘࡟ᑐࡍࡿ἞⒪ࡢ⌧≧࡜ၥ㢟Ⅼ 㛤Ⓨࡢ⤒⦋ 2.5.1.5 ⮫ᗋ㛤Ⓨ⤒⦋ 㠀⮫ᗋヨ㦂ࡢᴫ␎ 2.4 㠀⮫ᗋヨ㦂ࡢᴫᣓホ౯ ⏦ㄳຠ⬟࣭ຠᯝ࡟ᑐࡍࡿ᭷⏝ᛶ 2.5.6 ࣋ࢿࣇ࢕ࢵࢺ࡜ࣜࢫࢡ࡟㛵ࡍࡿ⤖ㄽ ⾲ 1.5-2 ရ㉁ཬࡧ㠀⮫ᗋ㛤Ⓨ࡟㛵ࡍࡿヨ㦂ࡢ㛤Ⓨ⤒⦋ ヨ㦂㡯┠ ᐇ᪋᫬ᮇ つ᱁ཬࡧヨ㦂᪉ἲ㸪ศᯒἲࣂࣜࢹ࣮ࢩࣙࣥ Ᏻᐃᛶ ཎ⸆ 〇๣ ⸆⌮ヨ㦂㻌 ຠຊࢆ⿬௜ࡅࡿヨ㦂 ๪ḟⓗ⸆⌮ヨ㦂 Ᏻ඲ᛶ⸆⌮ヨ㦂 ⸆ຊᏛⓗ⸆≀┦஫స⏝ヨ㦂 ⸆≀ືែヨ㦂㻌 ྾཰ ẘᛶヨ㦂㻌 ཯᚟ᢞ୚ẘᛶヨ㦂 ࡑࡢ௚ࡢẘᛶヨ㦂 ⤌⧊஺ᕪ཯ᛂᛶヨ㦂⾲ 1.5-3 ⮫ᗋヨ㦂ࡢ㛤Ⓨ⤒⦋ ┦ ᐇ᪋ ᆅᇦ ᑐ㇟ヨ㦂␒ྕ➼ ᐇ᪋᫬ᮇ I ᅜෆ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ 54767414MMY1002 㸦ホ౯㈨ᩱ㸧 2014 ᖺ 4 ᭶㹼2015 ᖺ 9 ᭶ Ib ᅜෆ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ 54767414MMY1005 㸦ホ౯㈨ᩱ㸧 2015 ᖺ 8 ᭶㹼⥅⥆୰ ᾏእ ᮍ἞⒪㸪෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ 㦵㧊⭘ 54767414MMY1001 㸦ཧ⪃㈨ᩱ㸧 2014 ᖺ 3 ᭶㹼⥅⥆୰ I/II ᾏእ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ GEN501 㸦ホ౯㈨ᩱ㸧 2008 ᖺ 3 ᭶㹼⥅⥆୰ ᾏእ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ GEN503 㸦ཧ⪃㈨ᩱ㸧 2012 ᖺ 6 ᭶㹼⥅⥆୰ II ᾏእ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ 54767414MMY2002 㸦ホ౯㈨ᩱ㸧 2013 ᖺ 9 ᭶㹼⥅⥆୰ III ᅜ㝿 ඹྠ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ 54767414MMY3003 㸦ホ౯㈨ᩱ㸧 2014 ᖺ 6 ᭶㹼⥅⥆୰ ᾏእ ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ 54767414MMY3004 㸦ホ౯㈨ᩱ㸧 2014 ᖺ 9 ᭶㹼⥅⥆୰

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ

1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ

ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧㸦௨ୗᮏ๣㸧ࡣ㸪༢๣⒪ἲ࡜ࡋ࡚ 2015 ᖺ 11 ᭶࡟⡿ᅜ࡛㸪2016 ᖺ 5 ᭶࡟ࡣḢᕞ࡛ᢎㄆࡉࢀ㸪2017 ᖺ 5 ᭶ 31 ᪥᫬Ⅼ࡛ 45 ࡢᅜ࡜ᆅᇦ࡛ᢎㄆࡉࢀ࡚࠸ࡿࠋᮏ๣ࡢే ⏝⒪ἲ࡜ࡋ࡚ࡣ㸪2016 ᖺ 11 ᭶࡟⡿ᅜ࡛㸪2017 ᖺ 4 ᭶࡟Ḣᕞ࡛ᢎㄆࡉࢀ࡚࠸ࡿࠋే⏝⒪ἲࡣ㸪 2017ᖺ 5 ᭶ 31 ᪥⌧ᅾ࡛ 34 ࡢᅜ࡜ᆅᇦ࡛ᢎㄆࡉࢀ࡚࠸ࡿࠋ ḟ࣮࣌ࢪ࡟㸪⡿ᅜཬࡧḢᕞ࡟࠾ࡅࡿᮏ๣ࡢᢎㄆ≧ἣࡢᴫせࢆ♧ࡍࠋࡲࡓ㸪እᅜࡢῧ௜ᩥ᭩࡜ࡋ ࡚㸪⡿ᅜཬࡧḢᕞࡢῧ௜ᩥ᭩㸪୪ࡧ࡟௻ᴗ୰᰾ࢹ࣮ࢱࢩ࣮ࢺ㸦CCDS㸧ࢆῧ௜ࡍࡿࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ⾲ 1.6-1 ⡿ᅜ࡟࠾ࡅࡿࢲࣛࢶ࣒࣐ࣈⅬ⁲㟼ὀ〇๣ࡢᢎㄆ≧ἣ ㈍኎ྡ DARZALEX ὀᑕᾮ ᢎㄆ᫬ᮇ 2015 ᖺ 11 ᭶㸦༢๣⒪ἲࡢᢎㄆ㸧㸪2016 ᖺ 11 ᭶㸦ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ ࢱࢰࣥ࡜ࡢే⏝⒪ἲ㸪୪ࡧ࡟࣎ࣝࢸࢰ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲ ࡢᢎㄆ㸧㸪2017 ᖺ 6 ᭶㸦࣏࣐ࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲࡢᢎ ㄆ㸧 ๣ᙧ࣭ྵ㔞 • 5 mLࣂ࢖࢔ࣝ୰㸪ࢲࣛࢶ࣒࣐ࣈ 100 mg ྵ᭷ • 20 mLࣂ࢖࢔ࣝ୰㸪ࢲࣛࢶ࣒࣐ࣈ 400 mg ྵ᭷ ຠ⬟࣭ຠᯝ ͌ᮏ๣㸪ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲ㸪ࡲࡓࡣᮏ๣㸪࣎ࣝࢸࢰ ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲ࡜ࡋ࡚㸪ᑡ࡞ࡃ࡜ࡶ 1 ࣞࢪ࣓ࣥ௨ୖࡢ๓἞ ⒪Ṕࢆ᭷ࡍࡿከⓎᛶ㦵㧊⭘ᝈ⪅࡟ᑐࡍࡿ἞⒪ ͌ࣞࢼࣜࢻ࣑ࢻཬࡧࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ⸆ࢆྵࡵ࡚ 2 ࣞࢪ࣓ࣥ௨ୖࡢ๓἞⒪Ṕࢆ ᭷ࡍࡿከⓎᛶ㦵㧊⭘ᝈ⪅࡟ᑐࡍࡿ࣏࣐ࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲ ͌ᮏ๣༢๣⒪ἲ࡜ࡋ࡚㸪ࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࢆྵࡴ 3 ࣞࢪ࣓ࣥ ௨ୖࡢ๓἞⒪Ṕࢆ᭷ࡍࡿ㸪ཪࡣࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࡢ୧๣࡟㞴 ἞ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅࡟ᑐࡍࡿ἞⒪ ⏝ἲ࣭⏝㔞 ᥎ዡ⏝㔞ཬࡧࢫࢣࢪ࣮ࣗࣝ ๓ᢞ⸆ཬࡧᚋᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ 0.9%ሷ໬ࢼࢺ࣒ࣜ࢘ὀᑕᾮ㸦USP㸧࡛ᕼ㔘ᚋ㸪Ⅼ⁲㟼ὀ࡜ࡋ࡚ࡢࡳᢞ୚ࡍࡿࡇ ࡜ࠋ DARZALEXࡣ་⒪ᚑ஦⪅ࡀᢞ୚ࡋ㸪ᩆᛴ་⒪ᶵჾཬࡧ㐺ษ࡞་⒪ࢧ࣏࣮ࢺࢆ┤ ࡕ࡟ཷࡅࡽࢀࡿࡼ࠺࡟ࡋ㸪Infusion reaction ࡀ㉳ࡇࡗࡓሙྜ࡟ᑐฎ࡛ࡁࡿࡼ࠺࡟ࡋ ࡚࠾ࡃࡇ࡜ࠋ ༢๣⒪ἲ࠶ࡿ࠸ࡣࣞࢼࣜࢻ࣑ࢻཪࡣ࣏࣐ࣜࢻ࣑ࢻཬࡧప⏝㔞ࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ ࡢే⏝⒪ἲ㸦1 ࢧ࢖ࢡࣝ 4 㐌㛫㝸ࡢࣞࢪ࣓ࣥ㸧 DARZALEXࡢ᥎ዡ⏝㔞ࡣ 16 mg/kg య㔜࡛࠶ࡾ㸪௨ୗࡢ⾲ 1ࡢᢞ୚ࢫࢣࢪ࣮ࣗࣝ ࡟ᚑࡗ࡚Ⅼ⁲㟼ὀࡍࡿࠋ ⾲ 1㸸DARZALEX ࡢᢞ୚ࢫࢣࢪ࣮ࣗࣝ 㐌 ࢫࢣࢪ࣮ࣗࣝ 1㹼8 㐌 ẖ㐌㸦ィ 8 ᅇᢞ୚㸧 9㹼24 㐌a 2㐌㛫㝸㸦ィ 8 ᅇᢞ୚㸧 25㐌௨㝆㸪⑌ᝈ㐍⾜ࡲ࡛b 4㐌㛫㝸 a. 2㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 9 㐌┠ b. 4㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 25 㐌┠ ࣎ࣝࢸࢰ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝⒪ἲ㸦1 ࢧ࢖ࢡࣝ 3 㐌㛫㝸ࡢࣞࢪ࣓ ࣥ㸧 DARZALEXࡢ᥎ዡ⏝㔞ࡣ 16 mg/kg య㔜࡛࠶ࡾ㸪௨ୗࡢ⾲ 2ࡢᢞ୚ࢫࢣࢪ࣮ࣗࣝ ࡟ᚑࡗ࡚Ⅼ⁲㟼ὀࡍࡿࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX ὀᑕᾮ ⾲ 2㸸 DARZALEX ࡢᢞ୚ࢫࢣࢪ࣮ࣗࣝ 㐌 ࢫࢣࢪ࣮ࣗࣝ 1㹼9 㐌 ẖ㐌㸦ィ 9 ᅇᢞ୚㸧 10㹼24 㐌a 3㐌㛫㝸㸦ィ 5 ᅇᢞ୚㸧 25㐌௨㝆㸪⑌ᝈ㐍⾜ࡲ࡛b 4㐌㛫㝸 a. 3㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 10 㐌┠ b. 4㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 25 㐌┠ DARZALEXࢆᢞ୚࡛ࡁ࡞࠿ࡗࡓሙྜ ணᐃ࡝࠾ࡾ DARZALEX ࢆᢞ୚࡛ࡁ࡞࠿ࡗࡓሙྜࡣ㸪࡛ࡁࡿ㝈ࡾ᪩ࡃࡑࡢᢞ୚ ࢆ⾜࠸㸪ᢞ୚ࢫࢣࢪ࣮ࣗࣝࢆ㐺ᐅㄪᩚࡋ࡚ᢞ୚㛫㝸ࢆ⥔ᣢࡍࡿࡇ࡜ࠋ ᢞ୚㏿ᗘཬࡧ Infusion reaction ࡢ⟶⌮ DARZALEXࡣ㸪௨ୗࡢ⾲ 3࡟♧ࡍᢞ୚㏿ᗘ࡛Ⅼ⁲㟼ὀࡍࡿࡇ࡜ࠋᢞ୚㏿ᗘࡢ ₞ቑ࡟ࡘ࠸࡚ࡣ㸪Infusion reaction ࢆⓎ⌧ࡋࡓࡇ࡜ࡢ࡞࠸ሙྜࡢࡳ᳨ウࡍࡿࡇ࡜ࠋ ⾲ 3 ᮏ๣ᢞ୚㏿ᗘ ᕼ㔘ᾮᐜ㔞 ึᅇᢞ୚㏿ᗘ 㸦᭱ึࡢ 1 ᫬㛫㸧 ᢞ୚㏿ᗘቑຍᖜa ᭱኱ᢞ୚㏿ᗘ ึᅇᢞ୚ 1000 mL 50 mL/᫬ 1᫬㛫ẖ࡟ 50 mL/᫬ 200 mL/᫬ 2ᅇ┠ࡢᢞ୚b 500 mL 50 mL/᫬ 1᫬㛫ẖ࡟ 50 mL/᫬ 200 mL/᫬ 3ᅇ┠௨㝆ࡢᢞ୚c _{500 mL} _{100 mL/᫬} ₁_{᫬㛫ẖ࡟ 50} mL/᫬ 200 mL/᫬ a. ᢞ୚㏿ᗘࡢ₞ቑ࡟ࡘ࠸࡚ࡣ㸪Infusion reaction ࢆⓎ⌧ࡋࡓࡇ࡜ࡢ࡞࠸ሙྜࡢࡳ᳨ウࡍࡿࡇ࡜ࠋ b. ึᅇᢞ୚ᚋ 3 ᫬㛫௨ෆ࡟ Grade 1㸦㍍ᗘ㸧௨ୖࡢ Infusion reaction ࡀ࡞࠸ሙྜࡢࡳᕼ㔘ᾮ⏝㔞 500 mL ࢆ

౑⏝ࡍࡿࡇ࡜ࠋࡑࢀ௨እࡢሙྜࡣᕼ㔘ᾮ⏝㔞 1000 mL ཬࡧึᅇᢞ୚᪉ἲࢆ⥅⥆ࡋ࡚⏝࠸ࡿࠋ c. ึᅇᢞ୚ཬࡧ 2 ᅇ┠ࡢᢞ୚࡛᭱⤊ᢞ୚㏿ᗘࡀ 100 mL/᫬௨ୖ࡜࡞ࡗ࡚࠸ࡿ㛫୰࡟ Grade 1㸦㍍ᗘ㸧௨ୖ ࡢ Infusion reaction ࡀ࡞࠸ሙྜࡢࡳ㸪3 ᅇ┠௨㝆ࡢึᅇᢞ୚㏿ᗘࢆㄪ⠇ࡍࡿࠋࡑࢀ௨እࡢሙྜࡣ 2 ᅇ┠ ࡢᢞ୚᪉ἲࢆ⥅⥆ࡋ࡚⏝࠸ࡿࠋ Grade㸭㔜⑕ᗘࢆၥࢃࡎ㸪Infusion reaction ࡀࡳࡽࢀࡓሙྜࡣ㸪ᮏ๣ࡢᢞ୚ࢆ┤ ࡕ࡟୰᩿ࡋ㸪⑕≧࡟ᑐฎࡍࡿࠋInfusion reaction ࡬ࡢᑐฎ࡟㝿ࡋ࡚ࡣ㸪௨ୗ࡟ᴫㄝ ࡢ࡜࠾ࡾ㸪ᢞ୚㏿ᗘࡢపୗཪࡣᢞ୚୰Ṇࡀᚲせ࡜࡞ࡿࡇ࡜ࡀ࠶ࡿࠋ

· Grade 1㹼2㸦㍍ᗘ㹼୰➼ᗘ㸧㸸Infusion reaction ࡟క࠺⑕≧ࡀᅇ᚟ḟ➨㸪

Infusion reactionࡀ㉳ࡇࡗࡓᢞ୚㏿ᗘࡢ༙ศ௨ୗࡢ㏿ᗘ࡛ᢞ୚ࢆ෌㛤ࡍࡿࡇ

࡜ࠋࡑࡢᚋ㸪Infusion reaction ࡟క࠺⑕≧ࡀⓎ⌧ࡋ࡞ࡅࢀࡤ㸪⮫ᗋⓗ࡟㐺ษ ࡞㸪᭱኱㏿ᗘ 200 mL/᫬ࡲ࡛ࡢቑຍᖜ࡜㛫㝸࡛ቑ㔞ࢆ෌㛤ࡋ࡚ࡶࡼ࠸ 㸦⾲ 3㸧ࠋ

· Grade 3㸦㔜ᗘ㸧㸸Infusion reaction ࡟క࠺⑕≧ࡀᅇ᚟ḟ➨㸪Infusion reaction ࡀⓎ⌧ࡋࡓ㏿ᗘࡢ༙ศ௨ୗ࡛ᢞ୚ࡢ෌㛤ࢆ᳨ウࡍࡿࡇ࡜ࠋࡑࡢᚋ㸪⑕≧ࡀ Ⓨ⌧ࡋ࡞ࡅࢀࡤ㸪⾲ 3 ࡟ᴫㄝࡢቑຍᖜ࡜㛫㝸࡛ᢞ୚㏿ᗘࡢ₞ቑࢆ෌㛤ࡍࡿ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ

㈍኎ྡ DARZALEX ὀᑕᾮ

ࡇ࡜ࠋGrade 3 ࡢ஦㇟࡟క࠺⑕≧ࡀ෌Ⓨࡍࡿሙྜࡣୖグࡢᡭ㡰ࢆ⧞ࡾ㏉ࡍࡇ ࡜ࠋGrade 3 ௨ୖࡢ Infusion reaction ࡀ 3 ᅇ㉳ࡇࡗࡓሙྜࡣ DARZALEX ࡢᢞ ୚ࢆỌ⥆ⓗ࡟୰Ṇࡍࡿࡇ࡜ࠋ · Grade 4㸦⏕࿨ࢆ⬣࠿ࡍ㸧㸸DARZALEX ࡢᢞ୚ࢆỌ⥆ⓗ࡟୰Ṇࡍࡿࡇ࡜ࠋ ᥎ዡే⏝⸆ ๓ᢞ⸆ Infusion reactionࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪ࡍ࡭࡚ࡢᝈ⪅࡟ᑐࡋ࡚㸪ẖᅇ㸪ᮏ๣ ᢞ୚ 1㹼3 ᫬㛫๓࡟㸪௨ୗࡢ๓ᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ · ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸦㛗᫬㛫ཪࡣ୰᫬㛫స⏝ᆺ㸧 ༢๣⒪ἲ ࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ 100 mg㸪ཪࡣ┦ᙜ㔞ࢆ㟼⬦ෆᢞ୚ࠋ2 ᅇ┠ࡢᢞ୚ᚋࡣ㸪 ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆῶ㔞ࡋ࡚ࡶⰋ࠸㸦࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ 60 mg ࢆ⤒ཱྀཪ ࡣ㟼⬦ෆᢞ୚㸧ࠋ ే⏝⒪ἲ ࢹ࢟ࢧ࣓ࢱࢰࣥ 20 mg ࢆ㸪ẖᅇ㸪ᮏ๣ᢞ୚᫬࡟๓ᢞ୚ࠋ ࢹ࢟ࢧ࣓ࢱࢰࣥࡣ㸪ᮏ๣ึᅇᢞ୚๓࡟ࡣ㟼⬦ෆᢞ୚ࡋ㸪2 ᅇ┠௨㝆ࡢ๓ᢞ୚࡟ ࡣ⤒ཱྀᢞ୚ࢆ᳨ウࡋ࡚ࡶⰋ࠸ࠋ · ゎ⇕๣㸦࢔ࢭࢺ࢔࣑ࣀࣇ࢙ࣥ 650 㹼1000 mg ⤒ཱྀᢞ୚㸧 · ᢠࣄࢫࢱ࣑ࣥ๣㸦ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ 25㹼50 mg ཪࡣ┦ᙜ㔞ࢆ⤒ཱྀཪࡣ㟼⬦ ෆᢞ୚㸧 ᚋᢞ⸆ 㐜Ⓨᛶ Infusion reaction ࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪ࡍ࡭࡚ࡢᝈ⪅࡟ᑐࡋ࡚㸪௨ ୗࡢ࡜࠾ࡾᚋᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ ༢๣⒪ἲ ᮏ๣ᢞ୚⤊஢ᚋࡣẖᅇ㸪⤒ཱྀࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸦࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ 20 mgཪࡣྠ➼㔞ࡢ୰᫬㛫ཪࡣ㛗᫬㛫స⏝ᆺࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆྛᆅᇦࡢᇶ ‽࡟ᛂࡌ࡚㸧ࢆ 2 ᪥㛫㐃᪥ᢞ୚ࡍࡿࡇ࡜㸦ᢞ୚⩣᪥࡟㛤ጞ㸧ࠋ ే⏝⒪ἲ ᮏ๣ᢞ୚ࡢ⩣᪥࡟ 20 mg ௨ୗࡢప⏝㔞࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ㸪ཪࡣ┦ᙜ㔞ࡢ⤒ ཱྀᢞ୚ࢆ᳨ウࡋ࡚ࡶⰋ࠸ࠋ ୍᪉㸪ᮏ๣ᢞ୚ࡢ⩣᪥࡟㸪ከⓎᛶ㦵㧊⭘⸆ࡢే⏝⸆࡜ࡋ࡚ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ 㸦౛࠼ࡤࢹ࢟ࢧ࣓ࢱࢰࣥ㸧ࢆᢞ୚ࡍࡿሙྜ࡟ࡣ㸪㏣ຍࡢᚋᢞ⸆ࡣᚲせ࡞࠸ሙྜ ࡀ࠶ࡿࠋ ࡉࡽ࡟៏ᛶ㛢ሰᛶ⫵⑌ᝈࡢ᪤ ࢆ᭷ࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣࡍ࡭࡚㸪▷᫬㛫స⏝ᆺ ཬࡧ㛗᫬㛫స⏝ᆺẼ⟶ᨭᣑᙇ๣ཬࡧ྾ධࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ࡜࠸ࡗࡓᚋᢞ୚ࡢฎ ᪉࡟ࡘ࠸࡚⪃៖ࡍࡿࡇ࡜ࠋ᭱ึࡢ 4 ᅇᢞ୚ࡋࡓᚋ㸪ᝈ⪅࡟㔜኱࡞ Infusion reaction ࡀⓎ⌧ࡋ࡚࠸࡞࠸ሙྜࡣ㸪௨㝆ࡣ྾ධ࡟ࡼࡿᚋᢞ⸆ࢆ୰Ṇࡋ࡚ࡶࡼ࠸ࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX ὀᑕᾮ ᖏ≧⑁⑈ࡢ෌⇞ண㜵 ᖏ≧⑁⑈ࡢ෌⇞ண㜵ࡢࡓࡵ㸪ᢠ࢘࢖ࣝࢫ⸆ண㜵ᢞ୚ࢆ DARZALEX ᢞ୚㛤ጞᚋ 1㐌㛫௨ෆ࡟㛤ጞࡋ㸪ᮏ἞⒪⤊஢ᚋࡶ 3 ࢝᭶㛫ᢞ୚ࡋ⥆ࡅࡿࡇ࡜ࠋ ⏝㔞ㄪ⠇ DARZALEXࡢῶ㔞ࡣ່ࡵࡽࢀ࡞࠸ࠋ⾑ᾮẘᛶࢆⓎ⌧ࡋࡓሙྜࡣ⾑⌫ᩘࡀᅇ᚟ ࡍࡿࡲ࡛ᢞ୚ࢆᚅࡗ࡚ࡶⰋ࠸ࠋDARZALEX ࡟ే⏝ࡍࡿ⸆๣࡟ࡘ࠸࡚ࡢ᝟ሗࡣ㸪〇㐀ᴗ⪅ࡢฎ᪉᝟ሗࢆཧ↷ࠋ ᢞ୚ࡢࡓࡵࡢㄪ〇 DARZALEXࡣ 1 ᅇ౑࠸ษࡾ࡛࠶ࡿࠋ ௨ୗࡢࡼ࠺࡟㸪↓⳦᧯సࢆ⾜ࡗࡓⅬ⁲⏝⁐ᾮࢆㄪ〇ࡍࡿࡇ࡜ࠋ · ᚲせ࡜ࡉࢀࡿ DARZALEX ⁐ᾮࡢᢞ୚㔞㸦mg㸧㸪⥲㔞㸦mL㸧㸪ཬࡧᚲせ࡞ DARZALEXࡢࣂ࢖࢔ࣝᩘࢆᝈ⪅ࡢᐇయ㔜࡟ᇶ࡙࠸࡚ィ⟬ࡍࡿࡇ࡜ࠋ · DARZALEX⁐ᾮࡀ↓Ⰽ㹼ᚤ㯤Ⰽ࡛࠶ࡿ࠿ࢆ☜ㄆࡍࡿࡇ࡜ࠋ୙㏱᫂࡞⢏Ꮚ㸪 ኚⰍ㸪ཪࡣࡑࡢ௚ࡢ␗≀ࡀ࠶ࡿሙྜࡣ౑⏝ࡋ࡞࠸ࡇ࡜ࠋ · DARZALEX⁐ᾮࡢᚲせ㔞࡜ྠᐜ㔞ࡢ⡿ᅜ⸆ᒁ᪉ 0.9%ሷ໬ࢼࢺ࣒ࣜ࢘ὀᑕᾮ ࢆ㍺ᾮࣂࢵࢢ࣭ᐜჾ࠿ࡽ㝖ཤࡍࡿࡇ࡜ࠋ · ᚲせ㔞ࡢ DARZALEX ⁐ᾮࢆᢤࡁྲྀࡾ㸪⾲ 3࡟グ㍕ࡢࡼ࠺࡟⡿ᅜ⸆ᒁ᪉ 0.9% ሷ໬ࢼࢺ࣒ࣜ࢘ὀᑕᾮࢆྵ᭷ࡍࡿ㍺ᾮࣂࢵࢢ࣭ᐜჾ࡟ຍ࠼ࡿࡇ࡜࡟ࡼࡾ㐺ษ ࡞ᐜ㔞࡟ᕼ㔘ࡍࡿࡇ࡜ࠋ㍺ᾮࣂࢵࢢ࣭ᐜჾࡣ㸪࣏ࣜሷ໬ࣅࢽࣝ㸪࣏ࣜࣉࣟࣆ ࣞࣥ㸪࣏࢚ࣜࢳࣞࣥ㸪ཪࡣ࣏ࣜ࢜ࣞࣇ࢕ࣥΰྜ≀㸦࣏ࣜࣉࣟࣆࣞࣥ+࣏࢚ࣜࢳ ࣞࣥ㸧〇ࡢ࠸ࡎࢀ࠿࡛࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ㐺ษ࡞↓⳦≧ែୗ࡛ᕼ㔘ࡍࡿࠋࣂ ࢖࢔ࣝࡢᮍ౑⏝ࡢṧᏑ⁐ᾮࡣ◚Რࡍࡿࡇ࡜ࠋ · ㍺ᾮࣂࢵࢢ࣭ᐜჾࢆ㟼࠿࡟཯㌿ࡉࡏ㸪⁐ᾮࢆΰྜࡍࡿࠋ᣺ࡾΰࡐ࡞࠸ࡇ࡜ࠋ · 㠀⤒ཱྀᢞ୚⸆ࡣࡑࡢ⁐ᾮཬࡧᐜჾ࡟࠾࠸࡚ྍ⬟࡞㝈ࡾ㸪ᢞ୚๓࡟⢏Ꮚ≧≀㉁ ཬࡧኚⰍࡢ᭷↓࡟ࡘ࠸࡚┠ど᳨ᰝࡍࡿࡇ࡜ࠋࢲࣛࢶ࣒࣐ࣈࡣ⺮ⓑ㉁࡛࠶ࡿࡓ ࡵ㸪ᕼ㔘⁐ᾮ࡟㠀ᖖ࡟ᑠࡉ࡞༙㏱᫂㹼ⓑⰍࡢ⺮ⓑᛶ⢏ᏊࡀⓎ⏕ࡍࡿࡇ࡜ࡀ࠶ ࡿࠋ୙㏱᫂࡞⢏Ꮚ㸪ኚⰍཪࡣࡑࡢ௚ࡢ␗≀ࡀ┠ど࡟ࡼࡾㄆࡵࡽࢀࡓሙྜࡣ౑ ⏝ࡋ࡞࠸ࡇ࡜ࠋ · DARZALEX࡟ࡣಖᏑ๣ࡣྵࡲࢀ࡚࠸࡞࠸ࡓࡵ㸪ᕼ㔘⁐ᾮࡣᐊ 㹙15㹼25|C 㸦59㹼77|F㸧㹛࠿ࡘᐊෆගୗ࡛┤ࡕ࡟ᢞ୚ࡍࡿࡇ࡜ࠋᕼ㔘⁐ᾮࡣᐊ ࡛᭱㛗 15᫬㛫㸦ᢞ୚᫬㛫ࢆྵࡴ㸧ಖᏑࡋ࡚ࡶⰋ࠸ࠋ · ┤ࡕ࡟ᢞ୚ࡋ࡞࠸ሙྜࡣ㸪ᢞ୚๓ࡢᕼ㔘⁐ᾮࡣ෭ⶶ㹙2㹼8|C㸦36㹼46|F㸧㹛 ࠿ࡘ㐽ගࡋ᭱㛗 24 ᫬㛫ಖᏑࡍࡿࡇ࡜ࡀ࡛ࡁࡿࠋ෾⤖ࡋ࡞࠸ࡇ࡜ࠋ ᢞ୚ · ෭ⶶಖᏑࡋࡓሙྜࡣ㸪⁐ᾮࢆᐊ ࡟ᡠࡍࠋ࢖ࣥࣛ࢖ࣥ㸪↓⳦㸪ࣃ࢖ࣟࢪ࢙ࣥ ࣇ࣮ࣜ㸪ཬࡧ⺮ⓑ⤖ྜᛶࡢప࠸࣏࢚࣮ࣜࢸࣝࢫࣝ࣍ࣥࣇ࢕ࣝࢱ࣮㸦Ꮝᚄ 0.22 ཪࡣ 0.2 ȝm㸧࡜ὶ㔞ㄪᩚᶵ⬟௜ࡁⅬ⁲ࢭࢵࢺࢆ౑⏝ࡋࡓⅬ⁲㟼ὀ࡟ࡼࡾᕼ㔘

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX ὀᑕᾮ ᾮࢆᢞ୚ࡍࡿࡇ࡜ࠋ࣏ࣜ࢘ࣞࢱࣥ㸪࣏ࣜࣈࢱࢪ࢚ࣥ㸪࣏ࣜሷ໬ࣅࢽࣝ㸪࣏ࣜ ࣉࣟࣆࣞࣥ㸪ཪࡣ࣏࢚ࣜࢳࣞࣥ〇ࡢ࠸ࡎࢀ࠿ࡢᢞ୚ࢭࢵࢺࢆ౑⏝ࡋ࡞ࡅࢀࡤ ࡞ࡽ࡞࠸ࠋ · ᮍ౑⏝ࡢⅬ⁲⁐ᾮࢆ෌฼⏝ࡢࡓࡵ࡟ಖᏑࡋ࡞࠸ࡇ࡜ࠋᮍ౑⏝〇ရཪࡣᗫᲠ≀ ࡣྛᆅᇦࡢつไせ௳࡟ᚑࡗ࡚ฎศࡍࡿࡇ࡜ࠋ · DARZALEXࢆ௚ࡢ⸆๣࡜ྠࡌ㟼⬦ࣛ࢖࡛ࣥే⏝ᢞ୚ࡋ࡞࠸ࡇ࡜ࠋ ⚗ᚷ ࡞ࡋ ㆙࿌ཬࡧ౑ ⏝ୖࡢὀព Infusion reaction

DARZALEXࡣ㸪㔜ᗘࡢ Infusion reaction ࢆᘬࡁ㉳ࡇࡍࡇ࡜ࡀ࠶ࡿࠋInfusion

reactionࡣ඲ᝈ⪅ࡢ⣙༙ᩘ࡛ࡳࡽࢀ㸪ࡑࡢ࡯࡜ࢇ࡝ࡣึᅇᢞ୚୰࡟Ⓨ⌧ࡋࡓࠋ

Infusion reactionࡣ㸪2 ᅇ┠௨㝆ࡢᢞ୚୰࡟ࡶ㉳ࡇࡿࡇ࡜ࡀ࠶ࡿࠋⅬ⁲୰ཪࡣ

DARZALEXᢞ୚⤊஢ᚋ 4 ᫬㛫௨ෆ࡟࡯ࡰࡍ࡭࡚ࡢ Infusion reaction ࡀࡳࡽࢀࡓࠋ ⮫ᗋヨ㦂࡟࠾ࡅࡿᚋᢞ⸆ࡢᑟධ๓࡛ࡣ㸪ᢞ୚ᚋ᭱㛗 48 ᫬㛫ࡲ࡛ Infusion reaction ࡀࡳࡽࢀࡓࠋ Ẽ⟶ᨭ②ᨥ㸪ప㓟⣲⑕㸪࿧྾ᅔ㞴㸪㧗⾑ᅽ㸪ႃ㢌ᾋ⭘㸪ཬࡧ⫵Ỉ⭘ࢆྵࡴ㔜ᗘ ࡢ Infusion reaction ࡀࡳࡽࢀࡓࠋᚩೃཬࡧ⑕≧࡟ࡣ㸪㰯㛢㸪တႿ㸪ဗႃ่⃭ឤ࡞ ࡝ࡢ࿧྾⑕≧㸪୪ࡧ࡟ᝏᐮ㸪჎ྤ㸪ཬࡧᝏᚰࡀྵࡲࢀࡿࡇ࡜ࡀ࠶ࡿࠋప㢖ᗘ࡛ࡳ ࡽࢀࡿ⑕≧࡟ࡣႍ㬆㸪࢔ࣞࣝࢠ࣮ᛶ㰯⅖㸪Ⓨ⇕㸪⬚㒊୙ᛌឤ㸪ࡑ࠺⑛⑕㸪ཬࡧప ⾑ᅽࡀ࠶ࡿࠋ ᢠࣄࢫࢱ࣑ࣥ๣㸪ゎ⇕๣㸪ཬࡧࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆ஦๓࡟ᝈ⪅࡟ᢞ୚ࡍࡿࡇ ࡜ࠋⅬ⁲㛤ጞ࠿ࡽ⤊஢ࡲ࡛ࡢ㛫୰㸪㢖⦾࡟ᝈ⪅ࢆࣔࢽࢱࣜࣥࢢࡍࡿࡇ࡜ࠋ㔜⑕ᗘ ࡟࠿࠿ࢃࡽࡎ Infusion reaction ࡀ㉳ࡇࡗࡓሙྜࡣ DARZALEX ࡢⅬ⁲ࢆ୰᩿ࡋ㸪ᚲ せ࡟ᛂࡌ࡚་Ꮫⓗ⟶⌮ࢆ㛤ጞࡍࡿࡇ࡜ࠋ⏕࿨ࢆ⬣࠿ࡍ Infusion reaction㸦Grade 4㸧ࡀ㉳ࡇࡗࡓሙྜࡣ DARZALEX ⒪ἲࢆ୰Ṇࡍࡿࡇ࡜ࠋGrade 1㸪2㸪ཪࡣ 3 ࡢ

Infusion reactionࡀࡳࡽࢀࡓᝈ⪅࡟ࡘ࠸࡚ࡣ㸪ᢞ୚㏿ᗘࢆୗࡆ࡚ᢞ୚෌㛤ࡍࡿࡇ

࡜ࠋ

㐜Ⓨᛶ Infusion reaction ࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪DARZALEX Ⅼ⁲⤊஢ᚋ ࡟㸪ࡍ࡭࡚ࡢᝈ⪅࡟ᑐࡋ⤒ཱྀࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆᢞ୚ࡍࡿࡇ࡜ࠋ៏ᛶ㛢ሰᛶ ⫵⑌ᝈࡢ᪤ ࢆ᭷ࡍࡿᝈ⪅࡟ࡣ㸪㏣ຍࡢᚋᢞ⸆ࢆ⾜࠸㸪࿧྾ჾྜే⑕࡬ࡢฎ⨨ ࡀᚲせ࡜࡞ࡿሙྜࡶ࠶ࡿࠋ៏ᛶ㛢ሰᛶ⫵⑌ᝈᝈ⪅࡟ࡘ࠸࡚ࡣ㸪▷᫬㛫ཬࡧ㛗᫬ 㛫స⏝ᆺẼ⟶ᨭᣑᙇ๣ཬࡧ྾ධࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࡢฎ᪉ࢆ᳨ウࡍࡿࡇ࡜ࠋ ච␿⾑Ύ᳨ᰝ࡬ࡢᖸ΅ ࢲࣛࢶ࣒࣐ࣈࡣ㉥⾑⌫ୖࡢ CD38 ࡟⤖ྜࡋ㸪㛫᥋ᢠࢢࣟࣈࣜࣥヨ㦂㸦㛫᥋ࢡ ࣮࣒ࢫヨ㦂㸧࡛㝧ᛶࢆ♧ࡍࠋࢲࣛࢶ࣒࣐ࣈࢆ௓ᅾࡋࡓ㛫᥋ᢠࢢࣟࣈࣜࣥヨ㦂⤖ ᯝࡣ㸪ࢲࣛࢶ࣒࣐ࣈࡢⅬ⁲⤊஢ᚋ᭱㛗 6 ࢝᭶㛫㝧ᛶ࡜࡞ࡿࡇ࡜ࡀ࠶ࡿࠋ㉥⾑⌫ ࡟⤖ྜࡋࡓࢲࣛࢶ࣒࣐ࣈࡣ㸪ᝈ⪅ࡢ⾑Ύ୰ࡢ๪ᢠཎ࡟ᑐࡍࡿᢠయࡢ᳨ฟࢆ㐽ⶸ ࡍࡿࠋᝈ⪅ࡢ ABO ᘧཬࡧ Rh ᘧ⾑ᾮᆺࡢุᐃ࡟ᙳ㡪ࡣ࡞࠸ࠋ ࡇࡢ⾑Ύヨ㦂࡬ࡢᖸ΅࡟ࡘ࠸࡚㍺⾑ࢭࣥࢱ࣮࡟㏻▱ࡋ㸪DARZALEX ࡀᝈ⪅࡟ ᢞ୚ࡉࢀࡓࡇ࡜ࢆ⾑ᾮࣂࣥࢡ࡟᝟ሗᥦ౪ࡍࡿࡇ࡜ࠋDARZALEX ࡢᢞ୚㛤ጞ๓ ࡟ᝈ⪅ࡢศ㢮ཬࡧࢫࢡ࣮ࣜࢽࣥࢢࢆᐇ᪋ࡍࡿࡇ࡜ࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX ὀᑕᾮ ዲ୰⌫ῶᑡ⑕ DARZALEXࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㉳ᅉࡍࡿዲ୰⌫ῶᑡ⑕ࡢⓎ⌧ࢆቑ ຍࡉࡏࡿྍ⬟ᛶࡀ࠶ࡿࠋ DARZALEXᢞ୚୰ࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㛵ࡍࡿ〇㐀ᴗ⪅ࡢฎ᪉᝟ሗ࡟ ᚑࡗ࡚㸪඲⾑⌫⟬ᐃࢆᐃᮇⓗ࡟ᐇ᪋ࡍࡿࠋዲ୰⌫ῶᑡ⑕ࢆ♧ࡋࡓᝈ⪅࡛ࡣឤᰁ ࡢᚩೃࢆࣔࢽࢱࣜࣥࢢࡍࡿࠋዲ୰⌫ࡀᅇ᚟ࡍࡿࡲ࡛ DARZALEX ࡢᢞ୚ࢆᚅࡗ࡚ ࡶⰋ࠸ࠋDARZALEX ࡢῶ㔞ࡣ່ࡵࡽࢀ࡞࠸ࠋᡂ㛗ᅉᏊ࡟ࡼࡿᨭᣢ⒪ἲࢆ⪃៖ࡍ ࡿࡇ࡜ࠋ ⾑ᑠᯈῶᑡ⑕ DARZALEXࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㉳ᅉࡍࡿ⾑ᑠᯈῶᑡ⑕ࡢⓎ⌧ࢆቑ ຍࡉࡏࡿྍ⬟ᛶࡀ࠶ࡿࠋ DARZALEXᢞ୚୰ࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㛵ࡍࡿ〇㐀ᴗ⪅ࡢฎ᪉᝟ሗ ࡟ᚑࡗ࡚㸪᏶඲⾑⌫⟬ᐃࢆᐃᮇⓗ࡟ᐇ᪋ࡍࡿࠋ⾑ᑠᯈࡀᅇ᚟ࡍࡿࡲ࡛ DARZALEXࡢᢞ୚ࢆᚅࡗ࡚ࡶⰋ࠸ࠋDARZALEX ࡢῶ㔞ࡣ່ࡵࡽࢀ࡞࠸ࠋ㍺⾑ ࡟ࡼࡿᨭᣢ⒪ἲࢆ⪃៖ࡍࡿࡇ࡜ࠋ ᏶඲ዌຠุᐃ࡬ࡢᖸ΅ ࢲࣛࢶ࣒࣐ࣈࡣ㸪ෆᅾᛶ M ⺮ⓑࡢ⮫ᗋࣔࢽࢱࣜࣥࢢ࡟౑⏝ࡉࢀࡿ⾑Ύ⺮ⓑ㟁 ẼὋືཬࡧච␿ᅛᐃἲࡢ୧᪉᳨࡛ฟྍ⬟࡞ࣄࢺᆺ IgG ț ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ ࡿࠋࡇࡢᖸ΅ࡣ IgG ț ᆺ㦵㧊⭘⺮ⓑࢆ᭷ࡍࡿᝈ⪅࡟ࡼࡗ࡚ࡣ᏶඲ዌຠཬࡧ⑌ᝈ㐍⾜ࡢุᐃ࡟ᙳ㡪ࢆཬࡰࡍྍ⬟ᛶࡀ࠶ࡿࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ⾲ 1.6-2 Ḣᕞ࡟࠾ࡅࡿࢲࣛࢶ࣒࣐ࣈⅬ⁲㟼ὀ〇๣ࡢᢎㄆ≧ἣ ㈍኎ྡ DARZALEX 20 mg/mLὀᑕ⏝⃰⦰〇๣ ᢎㄆ᫬ᮇ 2016 ᖺ 5 ᭶㸦༢๣⒪ἲ㸧㸪2017 ᖺ 4 ᭶㸦ే⏝⒪ἲ㸧 ๣ᙧ࣭ྵ㔞 • 5 mLࣂ࢖࢔ࣝ୰㸪ࢲࣛࢶ࣒࣐ࣈ 100 mg ྵ᭷ • 20 mLࣂ࢖࢔ࣝ୰㸪ࢲࣛࢶ࣒࣐ࣈ 400 mg ྵ᭷ ຠ⬟࣭ຠᯝ 㸦DARZALEX ༢๣⒪ἲ࡜ࡋ࡚㸧ࣉࣟࢸ࢔ࢯ࣮࣒㜼ᐖ๣ཬࡧච␿ㄪ⠇⸆ࢆྵࡴ๓ ἞⒪Ṕࢆ᭷ࡋ㸪┤㏆ࡢ἞⒪࡟ᑐࡋ࡚⑌ᝈ㐍⾜ࢆ♧ࡋࡓ෌Ⓨཪࡣ㞴἞ᛶࡢከⓎᛶ㦵㧊⭘ᡂேᝈ⪅ࡢ἞⒪ 㸦DARZALEX ే⏝⒪ἲ࡜ࡋ࡚㸧ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥཪࡣ࣎ࣝࢸࢰ ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ࡜ࡢే⏝࡛㸪1 ࣞࢪ࣓ࣥ௨ୖࡢ๓἞⒪Ṕࢆ᭷ࡍࡿከⓎᛶ 㦵㧊⭘ᡂேᝈ⪅ࡢ἞⒪ ⏝ἲ࣭⏝㔞 ⏝㔞 DARZALEXࡢ༢๣⒪ἲཬࡧࣞࢼࣜࢻ࣑ࢻ࡜ࡢే⏝⒪ἲࡢᶆ‽⏝㔞㸦4 㐌ࢧ࢖ ࢡࣝࣞࢪ࣓ࣥ㸧 DARZALEXࡢ᥎ዡ⏝㔞ࡣ 16 mg/kg య㔜࡛࠶ࡾ㸪௨ୗࡢ⾲1࡟♧ࡍᢞ୚ࢫࢣࢪࣗ ࣮ࣝ࡟ᚑࡗ࡚Ⅼ⁲㟼ὀࡍࡿࠋ ⾲ 1㸸DARZALEX ࡢ༢๣⒪ἲཬࡧࣞࢼࣜࢻ࣑ࢻ࡜ࡢే⏝⒪ἲࡢᶆ‽ⓗ࡞ ᢞ୚ࢫࢣࢪ࣮ࣗࣝ㸦4 㐌ࢧ࢖ࢡࣝࣞࢪ࣓ࣥ㸧㐌 ࢫࢣࢪ࣮ࣗࣝ 1㹼8 㐌┠ ẖ㐌㸦ィ 8 ᅇᢞ୚㸧 9㹼24 㐌┠a 2㐌㛫㝸㸦ィ 8 ᅇᢞ୚㸧 25㐌┠௨㝆㸪⑌ᝈ㐍⾜ࡲ࡛b 4㐌㛫㝸 a. 2㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 9 㐌┠ b. 4㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 25 㐌┠ ࣎ࣝࢸࢰ࣑ࣈ࡜ࡢే⏝⒪ἲࡢㄪᩚࡉࢀࡓᢞ୚ࢫࢣࢪ࣮ࣗࣝ㸦3 㐌ࢧ࢖ࢡࣝࣞࢪ ࣓ࣥ㸧 DARZALEXࡢ᥎ዡ⏝㔞ࡣ 16 mg/kg య㔜࡛࠶ࡾ㸪⾲ 2 ࡢᢞ୚ࢫࢣࢪ࣮ࣗࣝ࡟ᚑࡗ ࡚Ⅼ⁲㟼ὀࡍࡿࠋ ⾲ 2㸸DARZALEX ࡜࣎ࣝࢸࢰ࣑ࣈ࡜ࡢే⏝⒪ἲࡢㄪᩚࡉࢀࡓ ᢞ୚ࢫࢣࢪ࣮ࣗࣝ㸦3 㐌ࢧ࢖ࢡࣝࣞࢪ࣓ࣥ㸧㐌 ࢫࢣࢪ࣮ࣗࣝ 1㹼9 㐌┠ ẖ㐌㸦ィ 9 ᅇᢞ୚㸧 10㹼24 㐌┠a 3㐌㛫㝸㸦ィ 5 ᅇᢞ୚㸧 25㐌┠௨㝆㸪⑌ᝈ㐍⾜ࡲ࡛b 4㐌㛫㝸 a. 3㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 10 㐌┠ b. 4㐌㛫㝸ᢞ୚ࢫࢣࢪ࣮ࣗࣝࡢึᅇᢞ୚ࡣ 25 㐌┠ ᢞ୚㏿ᗘ DARZALEXࡣ㸪ᕼ㔘ᚋ㸪ୗグࡢ⾲ 3࡟♧ࡍึᅇᢞ୚㏿ᗘ࡛Ⅼ⁲㟼ὀ࡜ࡋ࡚ᢞ ୚ࡍࡿࡇ࡜ࠋᢞ୚㏿ᗘࡢ₞ቑ࡟ࡘ࠸࡚ࡣ㸪Infusion reaction ࢆⓎ⌧ࡋࡓࡇ࡜ࡢ࡞࠸ ሙྜࡢࡳ᳨ウࡍࡿࡇ࡜ࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX 20 mg/mLὀᑕ⏝⃰⦰〇๣ ⾲ 3㸸ᮏ๣ᢞ୚㏿ᗘ ᕼ㔘ᾮᐜ㔞 ึᅇᢞ୚㏿ᗘ 㸦᭱ึࡢ 1 ᫬ 㛫㸧 ᢞ୚㏿ᗘቑຍᖜa _{᭱኱ᢞ୚㏿ᗘ} ึᅇᢞ୚ 1000 mL 50 mL/᫬ 1᫬㛫ࡈ࡜࡟ 50 mL/᫬ 200 mL/᫬ 2ᅇ┠ࡢᢞ୚b 500 mL 50 mL/᫬ 1᫬㛫ࡈ࡜࡟ 50 mL/᫬ 200 mL/᫬ 3ᅇ┠௨㝆ࡢᢞ ୚c 500 mL 100 mL/᫬ 1᫬㛫ࡈ࡜࡟ 50 mL/᫬ 200 mL/᫬ a _{ᢞ୚㏿ᗘࡢ₞ቑ࡟ࡘ࠸࡚ࡣ㸪Infusion reaction ࢆⓎ⌧ࡋࡓࡇ࡜ࡢ࡞࠸ሙྜࡢࡳ᳨ウࡍࡿࡇ} ࡜ࠋ b

DARZALEXࡢึᅇᢞ୚࡟࠾࠸࡚㸪ᢞ୚ᚋ 3 ᫬㛫௨ෆ࡟ Grade 1 ௨ୖࡢ Infusion reaction ࡀⓎ⌧ࡋ࡞࠿ࡗࡓሙྜࡢࡳᕼ㔘ᾮ⏝㔞 500 mL ࢆ౑⏝ࡍࡿࡇ࡜ࠋࡑࢀ௨እࡢሙྜࡣᕼ㔘 ᾮ⏝㔞 1000 mL ཬࡧึᅇᢞ୚᪉ἲࢆ⥅⥆ࡋ࡚⏝࠸ࡿࠋ c DARZALEXࡢ᭱ึࡢ 2 ᅇࡢᢞ୚࡟࠾࠸࡚㸪100 mL/᫬௨ୖࡢ᭱⤊ᢞ୚㏿ᗘ࡛ Grade 1 ௨ ୖࡢ Infusion reaction ࡀⓎ⌧ࡋ࡞࠿ࡗࡓሙྜࡢࡳ 3 ᅇ┠௨㝆ࡢᢞ୚㏿ᗘࢆㄪ⠇ࡍࡿࠋࡑ ࢀ௨እࡢሙྜࡣ 2 ᅇ┠ࡢᢞ୚᪉ἲࢆ⥅⥆ࡋ࡚⏝࠸ࡿࠋ Infusion reactionࡢ⟶⌮ Infusion reactionࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪ᮏ๣ᢞ୚๓࡟๓ᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ Grade㸭㔜⑕ᗘࢆၥࢃࡎ㸪Infusion reaction ࡀࡳࡽࢀࡓሙྜࡣ㸪ᮏ๣ࡢᢞ୚ࢆ┤ ࡕ࡟୰᩿ࡋ㸪⑕≧࡟ᑐฎࡍࡿࠋ Infusion reaction࡬ࡢᑐฎ࡟㝿ࡋ࡚ࡣ㸪௨ୗ࡟ᴫㄝࡢ࡜࠾ࡾ㸪ᢞ୚㏿ᗘࡢపୗཪ ࡣᢞ୚୰Ṇࡀᚲせ࡜࡞ࡿࡇ࡜ࡀ࠶ࡿࠋ

· Grade 1㹼2㸦㍍ᗘ㹼୰➼ᗘ㸧㸸Infusion reaction ࡟క࠺⑕≧ࡀᅇ᚟ḟ➨㸪

Infusion reactionࡀ㉳ࡇࡗࡓᢞ୚㏿ᗘࡢ༙ศ௨ୗࡢ㏿ᗘ࡛ᢞ୚ࢆ෌㛤ࡍࡿࡇ

࡜ࠋࡑࡢᚋ㸪Infusion reaction ࡟క࠺⑕≧ࡀⓎ⌧ࡋ࡞ࡅࢀࡤ㸪⮫ᗋⓗ࡟㐺ษ ࡞᭱኱㏿ᗘ 200 mL/᫬ࡲ࡛ࡢቑຍᖜ࡜㛫㝸࡛ቑ㔞ࢆ෌㛤ࡋ࡚ࡶࡼ࠸㸦⾲ 3㸧ࠋ

· Grade 3㸦㔜ᗘ㸧㸸Infusion reaction ࡟క࠺⑕≧ࡀᅇ᚟ḟ➨㸪Infusion reaction ࡀⓎ⌧ࡋࡓ㏿ᗘࡢ༙ศ௨ୗ࡛ᢞ୚ࡢ෌㛤ࢆ᳨ウࡍࡿࡇ࡜ࠋࡑࡢᚋ㸪⑕≧ࡀ Ⓨ⌧ࡋ࡞ࡅࢀࡤ㸪㐺ษ࡞ቑຍᖜ࡜㛫㝸࡛ቑ㔞ࢆ෌㛤ࡋ࡚ࡶࡼ࠸㸦⾲ 3㸧ࠋ

Grade 3ࡢ஦㇟࡟క࠺⑕≧ࡀ෌Ⓨࡍࡿሙྜࡣୖグࡢᡭ㡰ࢆ⧞ࡾ㏉ࡍࡇ࡜ࠋ

Grade 3௨ୖࡢ Infusion reaction ࡀ 3 ᅇ㉳ࡇࡗࡓሙྜࡣ㸪DARZALEX ࡢᢞ୚ ࢆỌ⥆ⓗ࡟୰Ṇࡍࡿࡇ࡜ࠋ

· Grade 4㸦⏕࿨ࢆ⬣࠿ࡍ㸧㸸DARZALEX ࡢᢞ୚ࢆỌ⥆ⓗ࡟୰Ṇࡍࡿࡇ࡜ࠋ

ᢞ୚₃ࢀ

ணᐃ࡝࠾ࡾ DARZALEX ࢆᢞ୚࡛ࡁ࡞࠿ࡗࡓሙྜࡣ㸪࡛ࡁࡿ㝈ࡾ᪩ࡃࡑࡢᢞ୚ ࢆ⾜࠸㸪ᢞ୚ࢫࢣࢪ࣮ࣗࣝࢆ㐺ᐅㄪᩚࡋ࡚ᢞ୚㛫㝸ࢆ⥔ᣢࡍࡿࡇ࡜ࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX 20 mg/mLὀᑕ⏝⃰⦰〇๣ ⏝㔞ㄪ⠇ DARZALEXࡢῶ㔞ࡣ່ࡵࡽࢀ࡞࠸ࠋ⾑ᾮẘᛶࢆⓎ⌧ࡋࡓሙྜࡣ⾑⌫ᩘࡀᅇ᚟ ࡍࡿࡲ࡛ᢞ୚ࢆᚅࡗ࡚ࡶࡼ࠸ࠋDARZALEX ࡜ే⏝ࡍࡿ⸆๣࡟ࡘ࠸࡚ࡢ᝟ሗࡣ㸪ヱᙜࡍࡿ་⸆ရࡢ〇ရᴫせࢆཧ↷ࠋ ᥎ዡే⏝⸆ ๓ᢞ⸆ Infusion reactionࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪ࡍ࡭࡚ࡢᝈ⪅࡟ᑐࡋ࡚㸪ẖᅇ㸪ᮏ๣ ᢞ୚⣙ 1㹼3 ᫬㛫๓࡟㸪௨ୗࡢ࡜࠾ࡾ๓ᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ · ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸦୰᫬㛫స⏝ᆺཪࡣ㛗᫬㛫స⏝ᆺ㸧 ༢๣⒪ἲ㸸࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ 100 mg ཪࡣ┦ᙜ㔞ࢆ㟼⬦ෆᢞ୚ࠋ2 ᅇ ┠ࡢᢞ୚ᚋࡣ㸪ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆῶ㔞ࡋ࡚ࡶࡼ࠸㸦࣓ࢳࣝࣉࣞࢻࢽ ࢰࣟࣥ 60 mg ࢆ⤒ཱྀཪࡣ㟼⬦ෆᢞ୚㸧ࠋ ే⏝⒪ἲ㸸ࢹ࢟ࢧ࣓ࢱࢰࣥ 20 mg ࢆ㸪ẖᅇ㸪ᮏ๣ᢞ୚᫬࡟๓ᢞ୚ࠋࢹ࢟ ࢧ࣓ࢱࢰࣥࡣ㸪ᮏ๣ึᅇᢞ୚๓࡟ࡣ㟼⬦ෆᢞ୚ࡋ㸪2 ᅇ┠௨㝆ࡢ๓ᢞ୚ ࡟ࡣ⤒ཱྀᢞ୚ࢆ᳨ウࡋ࡚ࡶࡼ࠸ࠋ · ゎ⇕๣㸦ࣃࣛࢭࢱ࣮ࣔࣝ 650㹼1000 mg ࢆ⤒ཱྀᢞ୚㸧 · ᢠࣄࢫࢱ࣑ࣥ๣㸦ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ 25㹼50 mg ཪࡣ┦ᙜ㔞ࢆ⤒ཱྀཪࡣ㟼 ⬦ෆᢞ୚㸧 ᚋᢞ⸆ 㐜Ⓨᛶ Infusion reaction ࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪௨ୗࡢ࡜࠾ࡾᚋᢞ⸆ࢆ⾜࠺ ࡇ࡜ࠋ ༢๣⒪ἲ㸸ࡍ࡭࡚ࡢὀධࢆ⤊஢ᚋ 1 ᪥┠ཬࡧ 2 ᪥┠࡟㸦ὀධ⩣᪥࠿ࡽ㛤 ጞ㸧㸪⤒ཱྀࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸦࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ 20 mg ཪࡣ┦ᙜ㔞 ࡢ୰᫬㛫స⏝ᆺཪࡣ㛗᫬㛫స⏝ᆺࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆྛᆅᇦࡢᇶ‽࡟ᛂ ࡌ࡚㸧ࢆᢞ୚ࡍࡿࡇ࡜ࠋ ే⏝⒪ἲ㸸ᮏ๣ᢞ୚ࡢ⩣᪥࡟ప⏝㔞࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ㸦20 mg ௨ୗ㸧 ཪࡣ┦ᙜ㔞ࡢ⤒ཱྀᢞ୚ࢆ᳨ウࡋ࡚ࡶࡼ࠸ࠋࡓࡔࡋ㸪ᮏ๣ᢞ୚ࡢ⩣᪥࡟㸪ከ Ⓨᛶ㦵㧊⭘⸆ࡢే⏝⸆࡜ࡋ࡚ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸦౛࠼ࡤࢹ࢟ࢧ࣓ࢱࢰ ࣥ㸧ࢆᢞ୚ࡍࡿሙྜ࡟ࡣ㸪㏣ຍࡢᚋᢞ⸆ࡣᚲせ࡞࠸ሙྜࡀ࠶ࡿࠋ ៏ᛶ㛢ሰᛶ⫵⑌ᝈࡢ᪤ ࢆ᭷ࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣ㸪▷᫬㛫స⏝ᆺཬࡧ㛗᫬㛫స ⏝ᆺẼ⟶ᨭᣑᙇ๣ཬࡧ྾ධࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ࡜࠸ࡗࡓᚋᢞ୚ࡢ౑⏝࡟ࡘ࠸࡚⪃ ៖ࡍࡿࡇ࡜ࠋ᭱ึࡢ 4 ᅇࢆᢞ୚ࡋࡓᚋ㸪ᝈ⪅࡟㔜኱࡞ Infusion reaction ࡀⓎ⌧ࡋ ࡚࠸࡞࠸ሙྜࡣ㸪་ᖌࡢุ᩿࡟ࡼࡾ㸪ࡇࢀࡽࡢ྾ධ࡟ࡼࡿᚋᢞ⸆ࢆ୰Ṇࡋ࡚ࡶࡼ ࠸ࠋ ᖏ≧⑁⑈ࡢ෌⇞ண㜵 ᖏ≧⑁⑈ࡢ෌⇞ண㜵ࡢࡓࡵ㸪ᢠ࢘࢖ࣝࢫ⸆ࡢண㜵ᢞ୚ࢆ᳨ウࡍࡿࡇ࡜ࠋ ≉Ṧ㞟ᅋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX 20 mg/mLὀᑕ⏝⃰⦰〇๣ ⭈㞀ᐖᝈ⪅࡬ࡢᢞ୚ ⭈ᶵ⬟㞀ᐖᝈ⪅ࢆᑐ㇟࡜ࡋࡓࢲࣛࢶ࣒࣐ࣈࡢṇᘧ࡞ヨ㦂ࡣࡇࢀࡲ࡛ᐇ᪋ࡉࢀ࡚ ࠸࡞࠸ࠋẕ㞟ᅋ⸆≀ືែ㸦PK㸧ゎᯒ࡟ᇶ࡙ࡁ㸪⭈ᶵ⬟㞀ᐖᝈ⪅࡛ࡢ⏝㔞ㄪᩚࡣ ୙せ࡛࠶ࡿࠋ ⫢㞀ᐖᝈ⪅࡬ࡢᢞ୚ ⫢ᶵ⬟㞀ᐖᝈ⪅ࢆᑐ㇟࡜ࡋࡓࢲࣛࢶ࣒࣐ࣈࡢṇᘧ࡞ヨ㦂ࡣࡇࢀࡲ࡛ᐇ᪋ࡉࢀ࡚ ࠸࡞࠸ࠋ ẕ㞟ᅋ PK ゎᯒ࡟ᇶ࡙ࡁ㸪⫢ᶵ⬟㞀ᐖࢆ᭷ࡍࡿᝈ⪅࡛ࡢ⏝㔞ㄪᩚࡣ୙せ࡛࠶ ࡿࠋ 㧗㱋⪅࡬ࡢᢞ୚ 㧗㱋⪅࡛ࡢ⏝㔞ㄪᩚࡣ୙せ࡛࠶ࡿࠋ ᑠඣ࡬ࡢᢞ୚ 18ṓᮍ‶ࡢᑠඣᝈ⪅࡟ᑐࡍࡿ DARZALEX ࡢᏳ඲ᛶཬࡧ᭷ຠᛶࡣ☜❧ࡋ࡚࠸࡞ ࠸ࠋࢹ࣮ࢱࡣᚓࡽࢀ࡚࠸࡞࠸ࠋ ᢞ୚᪉ἲ DARZALEXࡣ㟼ὀ⏝〇๣࡛࠶ࡿࠋᮏ๣ࡣ㸪ሷ໬ࢼࢺ࣒ࣜ࢘ὀᑕᾮ 9 mg/mL 㸦0.9%㸧࡛ᕼ㔘ࡋ࡚࠿ࡽ㟼ὀࡍࡿࠋ ⚗ᚷ ᭷ຠᡂศཪࡣᮏ๣࡟ྵࡲࢀࡿῧຍ๣ࡢ࠸ࡎࢀ࠿࡟ᑐࡍࡿ㐣ᩄ⑕ࠋ ㆙࿌ཬࡧ౑ ⏝ୖࡢὀព Infusion reaction

Infusion reactionࡣ㸪DARZALEX ࢆᢞ୚ࡋࡓ඲ᝈ⪅ࡢ⣙༙ᩘ࡛ሗ࿌ࡉࢀࡓࠋ

Infusion reactionࡀ⌧ࢀࡓᝈ⪅ࡣ㸪ὀධ㛤ጞ࠿ࡽ⤊஢ࡲ࡛ࡢ㛫ཬࡧὀධᚋࡢᮇ㛫ࢆ

㏻ࡋ࡚ࣔࢽࢱࣜࣥࢢࡍࡿࠋ

Infusion reactionࡢ኱༙ࡣึᅇᢞ୚୰࡟Ⓨ⌧ࡋࡓࠋInfusion reaction ࡀ 2 ᅇ┠௨㝆 ࡢᢞ୚୰࡟⌧ࢀࡓᝈ⪅ࡣ඲ᝈ⪅ࡢ 4%࡛࠶ࡗࡓࠋẼ⟶ᨭ②ᨥ㸪ప㓟⣲⑕㸪࿧྾ᅔ 㞴㸪㧗⾑ᅽ㸪ႃ㢌ᾋ⭘㸪ཬࡧ⫵Ỉ⭘ࢆྵࡴ㔜ᗘࡢ Infusion reaction ࡀࡳࡽࢀࡓࠋ ⑕≧ࡣ୺࡟㰯㛢㸪တႿ㸪ဗႃ่⃭ឤ㸪ᝏᐮ㸪჎ྤ㸪ཬࡧᝏᚰ࡞࡝࡛࠶ࡗࡓࠋప㢖 ᗘ࡛ࡳࡽࢀࡓ⑕≧࡟ࡣႍ㬆㸪࢔ࣞࣝࢠ࣮ᛶ㰯⅖㸪Ⓨ⇕㸪⬚㒊୙ᛌឤ㸪ࡑ࠺⑛⑕ཬ ࡧప⾑ᅽࡀ࠶ࡗࡓࠋ Infusion reactionࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪ᢠࣄࢫࢱ࣑ࣥ๣㸪ゎ⇕๣㸪ཬࡧࢥࣝ ࢳࢥࢫࢸࣟ࢖ࢻࢆ㸪DARZALEX ࢆᢞ୚ࡍࡿ๓࡟ᝈ⪅࡟๓ᢞ⸆ࢆ⾜࠺ࡇ࡜ࠋ㔜⑕ ᗘ࡟࠿࠿ࢃࡽࡎ㸪Infusion reaction ࡀ㉳ࡇࡗࡓሙྜࡣ DARZALEX ࡢⅬ⁲ࢆ୰᩿ࡍ ࡿࡇ࡜ࠋᚲせ࡟ᛂࡌ࡚ Infusion reaction ࡢ་Ꮫⓗ⟶⌮/ᨭᣢ⒪ἲࢆ㛤ጞࡍࡿࡇ࡜ࠋ ᢞ୚ࢆ෌㛤ࡍࡿ㝿ࡣ㸪ᢞ୚㏿ᗘࢆୗࡆࡿࡇ࡜ࠋ

㐜Ⓨᛶ Infusion reaction ࡢࣜࢫࢡࢆ㍍ῶࡍࡿࡓࡵ㸪DARZALEX ࡢᢞ୚ᚋ㸪඲ᝈ ⪅࡟⤒ཱྀࢥࣝࢳࢥࢫࢸࣟ࢖ࢻࢆᢞ୚ࡍࡿࡇ࡜ࠋࡉࡽ࡟㸪៏ᛶ㛢ሰᛶ⫵⑌ᝈࡢ᪤  ࢆ᭷ࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣ㸪࿧྾ჾྜే⑕ࡀ㉳ࡇࡗࡓሙྜ࡟ഛ࠼࡚㸪ᚋᢞ⸆㸦྾ධ ࢥࣝࢳࢥࢫࢸࣟ࢖ࢻ㸪▷᫬㛫స⏝ᆺཬࡧ㛗᫬㛫స⏝ᆺẼ⟶ᨭᣑᙇ๣࡞࡝㸧ࡢ౑⏝ ࡟ࡘ࠸࡚⪃៖ࡍࡿࡇ࡜ࠋ ⏕࿨ࢆ⬣࠿ࡍ஦㇟ࡀ⌧ࢀࡓሙྜࡣ㸪DARZALEX ࡢᢞ୚ࢆỌ⥆ⓗ࡟୰Ṇࡍࡿࡇ ࡜ࠋ

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ࢲࣛࢶ࣒࣐ࣈ 1.6 እᅜ࡟࠾ࡅࡿ౑⏝≧ἣ➼࡟㛵ࡍࡿ㈨ᩱ ㈍኎ྡ DARZALEX 20 mg/mLὀᑕ⏝⃰⦰〇๣ ዲ୰⌫ῶᑡ⑕㸭⾑ᑠᯈῶᑡ⑕ DARZALEXࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㉳ᅉࡍࡿዲ୰⌫ῶᑡ⑕ཬࡧ⾑ᑠᯈ ῶᑡ⑕ࡢⓎ⌧ࢆቑຍࡉࡏࡿྍ⬟ᛶࡀ࠶ࡿࠋ DARZALEXᢞ୚୰ࡣ㸪ే⏝ࡍࡿከⓎᛶ㦵㧊⭘⸆࡟㛵ࡍࡿ〇㐀ᴗ⪅ࡢฎ᪉᝟ሗ ࡟ᚑࡗ࡚㸪඲⾑⌫⟬ᐃࢆᐃᮇⓗ࡟ᐇ᪋ࡍࡿࠋዲ୰⌫ῶᑡ⑕ࢆ♧ࡋࡓᝈ⪅࡛ࡣឤᰁ ࡢᚩೃࢆࣔࢽࢱࣜࣥࢢࡍࡿࠋ⾑⌫ᩘࡀᅇ᚟ࡍࡿࡲ࡛ DARZALEX ࡢᢞ୚ࢆᚅࡗ࡚ ࡶࡼ࠸ࠋDARZALEX ࡢῶ㔞ࡣ່ࡵࡽࢀ࡞࠸ࠋ㍺⾑ཪࡣᡂ㛗ᅉᏊ࡟ࡼࡿᨭᣢ⒪ἲ ࢆ⪃៖ࡍࡿࡇ࡜ࠋ 㛫᥋ᢠࢢࣟࣈࣜࣥヨ㦂㸦㛫᥋ࢡ࣮࣒ࢫヨ㦂㸧࡬ࡢᖸ΅ ࢲࣛࢶ࣒࣐ࣈࡣ㉥⾑⌫㸦RBC㸧ୖ࡟ప࡛ࣞ࣋ࣝⓎ⌧ࡋࡓ CD38 ࡟⤖ྜࡋ㸪㛫᥋ ࢡ࣮࣒ࢫヨ㦂࡛㝧ᛶࢆ♧ࡍሙྜࡀ࠶ࡿࠋࢲࣛࢶ࣒࣐ࣈࢆ௓ᅾࡋࡓ㛫᥋ࢡ࣮࣒ࢫヨ㦂⤖ᯝࡣ㸪ࢲࣛࢶ࣒࣐ࣈࡢⅬ⁲⤊஢ᚋ᭱㛗 6 ࢝᭶㛫㝧ᛶ࡜࡞ࡿࡇ࡜ࡀ࠶ࡿࠋRBC ࡟⤖ྜࡋࡓࢲࣛࢶ࣒࣐ࣈࡣ㸪ᝈ⪅ࡢ⾑Ύ୰ࡢ๪ᢠཎ࡟ᑐࡍࡿᢠయࡢ᳨ฟࢆ㐽ⶸࡍ ࡿሙྜࡀ࠶ࡿࡇ࡜ࢆㄆ㆑ࡍࡿࡇ࡜ࠋᝈ⪅ࡢ ABO ᘧཬࡧ Rh ᘧ⾑ᾮᆺࡢุᐃ࡟ᙳ 㡪ࡣ࡞࠸ࠋ ࢲࣛࢶ࣒࣐ࣈࡢᢞ୚㛤ጞ๓࡟ᝈ⪅ࡢศ㢮ཬࡧࢫࢡ࣮ࣜࢽࣥࢢࢆᐇ᪋ࡍࡿࡇ࡜ࠋ ᆅᇦࡢᇶ‽࡟ᛂࡌ࡚㸪ࢲࣛࢶ࣒࣐ࣈࡢᢞ୚㛤ጞ๓࡟⾲⌧ᆺ᳨ᰝࢆ᳨ウࡍࡿࡇ࡜ࠋ ㉥⾑⌫ࡢ⾲⌧ᆺ᳨ᰝࡣࢲࣛࢶ࣒࣐ࣈ࡟ᙳ㡪ࡉࢀࡿࡇ࡜ࡣ࡞ࡃ㸪࠸ࡘᐇ᪋ࡋ࡚ࡶࡼ ࠸ࠋ ணᐃࡉࢀࡓ㍺⾑ࡢ㝿࡟ࡣ㸪ࡇࡢ㛫᥋ᢠࢢࣟࣈࣜࣥヨ㦂࡬ࡢᖸ΅࡟ࡘ࠸࡚㍺⾑ࢭ ࣥࢱ࣮࡟㏻▱ࡍࡿࡇ࡜ࠋ⥭ᛴ㍺⾑ࡀᚲせ࡟࡞ࡗࡓሙྜࡣ㸪ྛᆅᇦࡢ⾑ᾮࣂࣥࢡ࡛ ࡢᡭ㡰࡟ᚑ࠸㸪஺ᕪ㐺ྜࡢ࡞࠸ ABO㸭RhD ࡟ྜ⮴ࡋࡓ RBC ࢆ㍺⾑ࡋ࡚ࡶࡼ࠸ࠋ ᏶඲ዌຠุᐃ࡬ࡢᖸ΅ ࢲࣛࢶ࣒࣐ࣈࡣ㸪ෆᅾᛶ M ⺮ⓑࡢ⮫ᗋࣔࢽࢱࣜࣥࢢ࡟౑⏝ࡉࢀࡿ⾑Ύ⺮ⓑ㟁 ẼὋືཬࡧච␿ᅛᐃἲࡢ୧᪉᳨࡛ฟྍ⬟࡞ࣄࢺ IgG ț ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ ࡿࠋࡇࡢᖸ΅ࡣ IgG ț ᆺ㦵㧊⭘⺮ⓑࢆ᭷ࡍࡿᝈ⪅࡟ࡼࡗ࡚ࡣ᏶඲ዌຠཬࡧ⑌ᝈ㐍⾜ࡢุᐃ࡟ᙳ㡪ࢆཬࡰࡍྍ⬟ᛶࡀ࠶ࡿࠋ ῧຍ๣ DARZALEXࡢ 5 mL ཬࡧ 20 mL ࣂ࢖࢔ࣝ࡟ࡣ㸪ࢼࢺ࣒ࣜ࢘ࡀࡑࢀࡒࢀ 0.4 mmoL㸪1.6 mmoL㸦9.3 mg㸪37.3 mg㸧ྵࡲࢀ࡚࠸ࡿࠋ㣗஦ࡢሷศࢆไ㝈ࡋ࡚ ࠸ࡿᝈ⪅ࡣ㸪ࡇࡢⅬࢆ⪃៖࡟ධࢀࡿࡇ࡜ࠋ

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Janssen Research & Development, LLC

COMPANY CORE DATA SHEET

Daratumumab

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DARZALEX®_{safely and effectively. See full prescribing information for} DARZALEX.

DARZALEX (daratumumab) injection, for intravenous use Initial U.S. Approval – 2015

---RECENT MAJOR CHANGES---Indications and Usage (1) 11/2016 Indications and Usage (1) 06/2017 Dosage and Administration (2.2, 2.3, 2.4) 11/2016 Dosage and Administration (2.1) 06/2017 Warnings and Precautions (5.1, 5.3, 5.4) 11/2016 ---INDICATIONS AND USAGE---DARZALEX is a CD38-directed cytolytic antibody indicated:

! in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy

! in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor

! as monotherapy, for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent. (1)

---DOSAGE AND ADMINISTRATION---Pre-medicate with corticosteroids, antipyretics and antihistamines. (2.2) Dilute and administer as an intravenous infusion. (2.4, 2.5)

Recommended dose is 16 mg/kg actual body weight according to the following schedule.

Monotherapy and in combination with lenalidomide or pomalidomide and low-dose dexamethasone:

Weeks 1 to 8 weekly (total of 8 doses) Weeks 9 to 24 every two weeks (total of 8 doses) Week 25 onwards until disease

progression

every four weeks

In combination with bortezomib and dexamethasone:

Weeks 1 to 9 weekly (total of 9 doses)

Weeks 10 to 24 every three weeks (total of 5 doses) Week 25 onwards until disease

progression

every four weeks Administer post-infusion medications. (2.2)

---DOSAGE FORMS AND STRENGTHS---Injection:

! 100 mg/5 mL solution in a single-dose vial (3) ! 400 mg/20 mL solution in a single-dose vial (3)

---CONTRAINDICATIONS---None.

---WARNINGS AND PRECAUTIONS---! Infusion reactions: Interrupt DARZALEX infusion for infusion reactions of

any severity. Permanently discontinue the infusion in case of life-threatening infusion reactions. (2.1, 5.1)

! Interference with cross-matching and red blood cell antibody screening: Type and screen patients prior to starting treatment. Inform blood banks that a patient has received DARZALEX. (5.2, 7.1)

! Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Dose delay may be required to allow recovery of neutrophils. (5.3)

! Thrombocytopenia: Monitor complete blood cell counts periodically during treatment. Dose delay may be required to allow recovery of platelets. (5.4) ---ADVERSE REACTIONS---The most frequently reported adverse reactions (incidence ≥20%) in clinical trials were: infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy and upper respiratory tract infection. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 6/2017 FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose and Schedule 2.2 Recommended Concomitant Medications 2.3 Dose Modifications

2.4 Preparation for Administration 2.5 Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Infusion Reactions

5.2 Interference with Serological Testing 5.3 Neutropenia

5.4 Thrombocytopenia

5.5 Interference with Determination of Complete Response

6 ADVERSE REACTIONS

6.1 Adverse Reactions in Clinical Trials 6.2 Immunogenicity

7 DRUG INTERACTIONS

7.1 Effects of Daratumumab on Laboratory Tests

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy 8.2 Lactation

8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Combination Treatment with Lenalidomide and Dexamethasone

14.2 Combination Treatment with Bortezomib and Dexamethasone

14.3 Combination Treatment with Pomalidomide and Dexamethasone

14.4 Monotherapy

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied 16.2 Storage and Stability

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

(20)

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

DARZALEX is indicated:

!

in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone,

for the treatment of patients with multiple myeloma who have received at least one prior

therapy.

!

in combination with pomalidomide and dexamethasone for the treatment of patients with

multiple myeloma who have received at least two prior therapies including lenalidomide and

a proteasome inhibitor.

!

as monotherapy, for the treatment of patients with multiple myeloma who have received at

least three prior lines of therapy including a proteasome inhibitor (PI) and an

immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory

agent.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose and Schedule

!

Administer pre-infusion and post-infusion medications [see Dosage and Administration

(2.2)].

!

Administer only as an intravenous infusion after dilution in 0.9% Sodium Chloride Injection,

USP [see Dosage and Administration (2.4, 2.5)].

!

DARZALEX should be administered by a healthcare professional, with immediate access to

emergency equipment and appropriate medical support to manage infusion reactions if they

occur [see Warnings and Precautions (5.1)].

Monotherapy and Combination Therapy with Lenalidomide or Pomalidomide and

Low-Dose Dexamethasone (4-week cycle regimens)

The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an

intravenous infusion according to the following dosing schedule in Table 1:

Table 1: DARZALEX dosing schedule for monotherapy and in combination with lenalidomide or pomalidomide (4-week cycle dosing regimens)

Weeks Schedule

Weeks 9 to 24a every two weeks (total of 8 doses)

Week 25 onwards until disease progressionb every four weeks

a _{First dose of the every-2-week dosing schedule is given at week 9} b _{First dose of the every-4-week dosing schedule is given at week 25}

(21)

For dosing instructions of combination agents administered with DARZALEX, see Clinical

Studies (14.1, 14.3) and manufacturer’s prescribing information.

Combination Therapy with Bortezomib and Dexamethasone (3-week cycle regimen)

The recommended dose of DARZALEX is 16 mg/kg actual body weight administered as an

intravenous infusion according to the following dosing schedule in Table 2:

Table 2: DARZALEX dosing schedule with bortezomib (3-week cycle dosing regimen)

Weeks Schedule

Weeks 10 to 24a _{every three weeks (total of 5 doses)}

Week 25 onwards until disease progressionb _{every four weeks} a _{First dose of the every-3-week dosing schedule is given at week 10} b _{First dose of the every-4-week dosing schedule is given at week 25}

For dosing instructions of combination agents administered with DARZALEX see Clinical

Studies (14.2) and manufacturer’s prescribing information.

Missed DARZALEX Doses

If a planned dose of DARZALEX is missed, administer the dose as soon as possible and adjust

the dosing schedule accordingly, maintaining the treatment interval.

Infusion Rates and Management of Infusion Reactions

Administer DARZALEX infusion intravenously at the infusion rate described below in Table 3.

Consider incremental escalation of the infusion rate only in the absence of infusion reactions.

Table 3:

Infusion rates for DARZALEX administration

Dilution

volume

Initial rate (first

hour)

Rate

increment

a

Maximum rate

First infusion

1000 mL

50 mL/hour

every hour

200 mL/hour

Second infusion

b

500 mL

50 mL/hour

every hour

200 mL/hour

Subsequent infusions

c

500 mL

100 mL/hour

50 mL/hour

every hour

200 mL/hour

a

Consider incremental escalation of the infusion rate only in the absence of infusion reactions. b

Use a dilution volume of 500 mL only if there were no Grade 1 (mild) or greater infusion reactions during the first 3 hours of the first infusion. Otherwise, continue to use a dilution volume of 1000 mL and instructions for the first infusion.

c

Use a modified initial rate for subsequent infusions (i.e. third infusion onwards) only if there were no Grade 1 (mild) or greater infusion reactions during a final infusion rate of ≥100 mL/hr in the first two infusions. Otherwise, continue to use instructions for the second infusion.

For infusion reactions of any grade/severity, immediately interrupt the DARZALEX infusion and

manage symptoms. Management of infusion reactions may further require reduction in the rate

(22)

of infusion, or treatment discontinuation of DARZALEX as outlined below [see Warnings and

Precautions (5.1)].

!

Grade 1-2 (mild to moderate): Once reaction symptoms resolve, resume the infusion at no

more than half the rate at which the reaction occurred. If the patient does not experience any

further reaction symptoms, infusion rate escalation may resume at increments and intervals

as clinically appropriate up to the maximum rate of 200 mL/hour (Table 3).

!

Grade 3 (severe): Once reaction symptoms resolve, consider restarting the infusion at no

more than half the rate at which the reaction occurred. If the patient does not experience

additional symptoms, resume infusion rate escalation at increments and intervals as outlined

in Table 3. Repeat the procedure above in the event of recurrence of Grade 3 symptoms.

Permanently discontinue DARZALEX upon the third occurrence of a Grade 3 or greater

infusion reaction.

!

Grade 4 (life threatening): Permanently discontinue DARZALEX treatment.

2.2 Recommended Concomitant Medications

Pre-infusion Medication

Administer the following pre-infusion medications to reduce the risk of infusion reactions to all

patients 1-3 hours prior to every infusion of DARZALEX:

!

Corticosteroid (long-acting or intermediate-acting)

Monotherapy:

Methylprednisolone 100 mg, or equivalent, administered intravenously. Following the

second infusion, the dose of corticosteroid may be reduced (oral or intravenous

methylprednisolone 60 mg).

Combination therapy:

Administer 20 mg dexamethasone prior to every DARZALEX infusion [Clinical Studies

(14)].

Dexamethasone is given intravenously prior to the first DARZALEX infusion and oral

administration may be considered prior to subsequent infusions.

!

Antipyretics (oral acetaminophen 650 to 1000 mg)

!

Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent).

Post-infusion Medication

Administer post-infusion medication to reduce the risk of delayed infusion reactions to all

patients as follows:

(23)

Monotherapy:

Administer oral corticosteroid (20 mg methylprednisolone or equivalent dose of an

intermediate-acting or long-acting corticosteroid in accordance with local standards) on

each of the 2 days following all DARZALEX infusions (beginning the day after the

infusion).

Combination therapy:

Consider administering low-dose oral methylprednisolone (≤ 20 mg) or equivalent, the

day after the DARZALEX infusion.

However, if a background regimen-specific corticosteroid (e.g. dexamethasone) is

administered the day after the DARZALEX infusion, additional post-infusion

medications may not be needed [see Clinical Studies (14)].

In addition, for any patients with a history of chronic obstructive pulmonary disease, consider

prescribing post-infusion medications such as short and long-acting bronchodilators, and inhaled

corticosteroids. Following the first four infusions, if the patient experiences no major infusion

reactions, these additional inhaled post-infusion medications may be discontinued.

Prophylaxis for Herpes Zoster Reactivation

Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week after starting

DARZALEX and continue for 3 months following treatment [see Adverse Reactions (6.1)].

2.3 Dose Modifications

No dose reductions of DARZALEX are recommended. Dose delay may be required to allow

recovery of blood cell counts in the event of hematological toxicity [see Warnings and

Precautions (5.3, 5.4)]. For information concerning drugs given in combination with

DARZALEX, see manufacturer’s prescribing information.

2.4 Preparation for Administration

DARZALEX is for single use only.

Prepare the solution for infusion using aseptic technique as follows:

!

Calculate the dose (mg), total volume (mL) of DARZALEX solution required and the

number of DARZALEX vials needed based on patient actual body weight.

!

Check that the DARZALEX solution is colorless to pale yellow. Do not use if opaque

particles, discoloration or other foreign particles are present.

!

Remove a volume of 0.9% Sodium Chloride Injection, USP from the infusion bag/container

that is equal to the required volume of DARZALEX solution.

(24)

!

Withdraw the necessary amount of DARZALEX solution and dilute to the appropriate

volume by adding to the infusion bag/container containing 0.9% Sodium Chloride Injection,

USP as specified in Table 3 [see Dosage and Administration (2.1)]. Infusion bags/containers

must be made of either polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE) or

polyolefin blend (PP+PE). Dilute under appropriate aseptic conditions. Discard any unused

portion left in the vial.

!

Gently invert the bag/container to mix the solution. Do not shake.

!

Parenteral drug products should be inspected visually for particulate matter and discoloration

prior to administration, whenever solution and container permit. The diluted solution may

develop very small, translucent to white proteinaceous particles, as daratumumab is a protein.

Do not use if visibly opaque particles, discoloration or foreign particles are observed.

!

Since DARZALEX does not contain a preservative, administer the diluted solution

immediately at room temperature 15°C–25°C (59°F–77°F) and in room light. Diluted

solution may be kept at room temperature for a maximum of 15 hours (including infusion

time).

!

If not used immediately, the diluted solution can be stored prior to administration for up to

24 hours at refrigerated conditions 2°C – 8°C (36°F–46°F) and protected from light. Do not

freeze.

2.5 Administration

!

If stored in the refrigerator, allow the solution to come to room temperature. Administer the

diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and

with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter

(pore size 0.22 or 0.2 micrometer). Administration sets must be made of either polyurethane

(PU), polybutadiene (PBD), PVC, PP or PE.

!

Do not store any unused portion of the infusion solution for reuse. Any unused product or

waste material should be disposed of in accordance with local requirements.

!

Do not infuse DARZALEX concomitantly in the same intravenous line with other agents.

3 DOSAGE FORMS AND STRENGTHS

DARZALEX is a colorless to pale yellow, preservative-free solution available as:

Injection:

!

100 mg/5 mL (20 mg/mL) in a single-dose vial.

(25)

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Infusion Reactions

DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced

a reaction, most during the first infusion.

Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during

infusion or within 4 hours of completing DARZALEX. Prior to the introduction of post-infusion

medication in clinical trials, infusion reactions occurred up to 48 hours after infusion.

Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension,

laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory symptoms,

such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less

common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and

hypotension [see Adverse Reactions (6.1)].

Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Frequently monitor

patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity

and institute medical management as needed. Permanently discontinue DARZALEX therapy for

life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the

infusion rate when re-starting the infusion [see Dosage and Administration (2.1)].

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients

following DARZALEX infusions [see Dosage and Administration (2.2)]. Patients with a history

of chronic obstructive pulmonary disease may require additional post-infusion medications to

manage respiratory complications. Consider prescribing short- and long-acting bronchodilators

and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

5.2 Interference with Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect

Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin

test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to

RBCs masks detection of antibodies to minor antigens in the patient’s serum

1

[see References

(15)]. The determination of a patient’s ABO and Rh blood type are not impacted [see Drug

Interactions (7.1)].

Notify blood transfusion centers of this interference with serological testing and inform blood

banks that a patient has received DARZALEX. Type and screen patients prior to starting

DARZALEX.

(26)

5.3 Neutropenia

DARZALEX may increase neutropenia induced by background therapy [see Adverse Reactions

(6.1)].

Monitor complete blood cell counts periodically during treatment according to manufacturer’s

prescribing information for background therapies. Monitor patients with neutropenia for signs of

infection. DARZALEX dose delay may be required to allow recovery of neutrophils. No dose

reduction of DARZALEX is recommended. Consider supportive care with growth factors.

5.4 Thrombocytopenia

DARZALEX may increase thrombocytopenia induced by background therapy [see Adverse

Reactions (6.1)].

Monitor complete blood cell counts periodically during treatment according to manufacturer’s

prescribing information for background therapies. DARZALEX dose delay may be required to

allow recovery of platelets. No dose reduction of DARZALEX is recommended. Consider

supportive care with transfusions.

5.5 Interference with Determination of Complete Response

Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the

serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical

monitoring of endogenous M-protein [see Drug Interactions (7.1)]. This interference can impact

the determination of complete response and of disease progression in some patients with IgG

kappa myeloma protein.

6 ADVERSE REACTIONS

The following serious adverse reactions are also described elsewhere in the labeling:

!

Infusion reactions [see Warning and Precautions (5.1)].

!

Neutropenia [see Warning and Precautions (5.3)].

!

Thrombocytopenia [see Warning and Precautions (5.4)].

6.1 Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates

observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials

of another drug and may not reflect the rates observed in practice.

The safety data described below reflects exposure to DARZALEX (16 mg/kg) in 820 patients

with multiple myeloma including 526 patients from two Phase 3 active-controlled trials who

received DARZALEX in combination with either lenalidomide (DRd, n=283; Study 3) or

bortezomib (DVd, n=243; Study 4) and five open-label, clinical trials in which patients received

(27)

DARZALEX either in combination with pomalidomide (DPd, n=103; Study 5), in combination

with lenalidomide (n=35), or as monotherapy (n=156).

Combination Treatment with Lenalidomide

Adverse reactions described in Table 4 reflect exposure to DARZALEX (DRd arm) for a median

treatment duration of 13.1 months (range: 0 to 20.7 months) and median treatment duration of

12.3 months (range: 0.2 to 20.1 months) for the lenalidomide group (Rd) in Study 3. The most

frequent adverse reactions (≥20%) were infusion reactions, diarrhea, nausea, fatigue, pyrexia,

upper respiratory tract infection, muscle spasms, cough and dyspnea. The overall incidence of

serious adverse reactions was 49% for the DRd group compared with 42% for the Rd group.

Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared to the

Rd arm were pneumonia (12% vs Rd 10%), upper respiratory tract infection (7% vs Rd 4%),

influenza and pyrexia (DRd 3% vs Rd 1% for each).

Adverse reactions resulted in discontinuations for 7% (n=19) of patients in the DRd arm versus

8% (n=22) in the Rd arm.

Table 4: Adverse reactions reported in ≥ 10% of patients and with at least a 5% frequency greater in the DRd arm in Study 3

Adverse Reaction DRd (N=283) % Rd (N=281) %

Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4

Infusion reactionsa ₄₈ ₅ ₀ ₀ ₀ ₀

Gastrointestinal disorders

Diarrhea 43 5 0 25 3 0

Nausea 24 1 0 14 0 0

Vomiting 17 1 0 5 1 0

General disorders and administration site conditions

Fatigue 35 6 < 1 28 2 0

Pyrexia 20 2 0 11 1 0

Infections and infestations Upper respiratory

tract infectionb ₆₅ ₆ _{< 1} ₅₁ ₄ ₀

Musculoskeletal and connective tissue disorders

Muscle spasms 26 1 0 19 2 0

Nervous system disorders

Headache 13 0 0 7 0 0

Respiratory, thoracic and mediastinal disorders

Coughc ₃₀ ₀ ₀ ₁₅ ₀ ₀

Dyspnead ₂₁ ₃ _{< 1} ₁₂ ₁ ₀

Key: D=daratumumab, Rd=lenalidomide-dexamethasone.

a _{Infusion reaction includes terms determined by investigators to be related to infusion, see description of Infusion Reactions}

below.

b _{upper respiratory tract infection, bronchitis, sinusitis, respiratory tract infection viral, rhinitis, pharyngitis, respiratory tract}

infection, metapneumovirus infection, tracheobronchitis, viral upper respiratory tract infection, laryngitis, respiratory syncytial virus infection, staphylococcal pharyngitis, tonsillitis, viral pharyngitis, acute sinusitis, nasopharyngitis, bronchiolitis, bronchitis viral, pharyngitis streptococcal, tracheitis, upper respiratory tract infection bacterial, bronchitis bacterial, epiglottitis, laryngitis viral, oropharyngeal candidiasis, respiratory moniliasis, viral rhinitis, acute tonsillitis, rhinovirus infection

c _{cough, productive cough, allergic cough} d _{dyspnea, dyspnea exertional}

(28)

Laboratory abnormalities worsening during treatment from baseline listed in Table 5.

Table 5: Treatment-emergent hematology laboratory abnormalities in Study 3 DRd (N=283) % Rd (N=281) %

Any Grade Grade 3 Grade 4 All Grades Grade 3 Grade 4

Anemia 52 13 0 57 19 0

Thrombocytopenia 73 7 6 67 10 5

Neutropenia 92 36 17 87 32 8

Lymphopenia 95 42 10 87 32 6

Key: D=Daratumumab, Rd=lenalidomide-dexamethasone.

Combination Treatment with Bortezomib

Adverse reactions described in Table 6 reflect exposure to DARZALEX (DVd arm) for a median

treatment duration of 6.5 months (range: 0 to 14.8 months) and median treatment duration of

5.2 months (range: 0.2 to 8.0 months) for the bortezomib group (Vd) in Study 4. The most

frequent adverse reactions (>20%) were infusion reactions, diarrhea, peripheral edema, upper

respiratory tract infection, peripheral sensory neuropathy, cough and dyspnea. The overall

incidence of serious adverse reactions was 42% for the DVd group compared with 34% for the

Vd group. Serious adverse reactions with at least a 2% greater incidence in the DVd arm

compared to the Vd arm were upper respiratory tract infection (DVd 5% vs Vd 2%), diarrhea and

atrial fibrillation (DVd 2% vs Vd 0% for each).

Adverse reactions resulted in discontinuations for 7% (n=18) of patients in the DVd arm versus

9% (n=22) in the Vd arm.

(29)

Table 6: Adverse reactions reported in ≥ 10% of patients and with at least a 5% frequency greater in the DVd arm Study 4

Adverse Reaction DVd (N=243) % Vd (N=237) %

Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4

Infusion reactionsa 45 9 0 0 0 0

Gastrointestinal disorders

Diarrhea 32 3 < 1 22 1 0

Vomiting 11 0 0 4 0 0

Edema peripheralb 22 1 0 13 0 0

Pyrexia 16 1 0 11 1 0

Infections and infestations Upper respiratory tract

infectionc 44 6 0 30 3 < 1

Nervous system disorders Peripheral sensory

neuropathy 47 5 0 38 6 < 1

Respiratory, thoracic and mediastinal disorders

Coughd 27 0 0 14 0 0

Dyspneae 21 4 0 11 1 0

Key: D=daratumumab, Vd=bortezomib-dexamethasone.

a

Infusion reaction includes terms determined by investigators to be related to infusion, see description of Infusion Reactions below.

b

edema peripheral, edema, generalized edema, peripheral swelling

c

upper respiratory tract infection, bronchitis, sinusitis, respiratory tract infection viral, rhinitis, pharyngitis, respiratory tract infection, metapneumovirus infection, tracheobronchitis, viral upper respiratory tract infection, laryngitis, respiratory syncytial virus infection, staphylococcal pharyngitis, tonsillitis, viral pharyngitis, acute sinusitis, nasopharyngitis, bronchiolitis, bronchitis viral, pharyngitis streptococcal, tracheitis, upper respiratory tract infection bacterial, bronchitis bacterial, epiglottitis, laryngitis viral, oropharyngeal candidiasis, respiratory moniliasis, viral rhinitis, acute tonsillitis, rhinovirus infection

d

cough, productive cough, allergic cough

e

dyspnea, dyspnea exertional

Laboratory abnormalities worsening during treatment are listed in Table 7.

Table 7: Treatment-emergent hematology laboratory abnormalities in Study 4 DVd (N=243) % Vd (N=237) %

Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4

Anemia 48 13 0 56 14 0

Thrombocytopenia 90 28 19 85 22 13

Neutropenia 58 12 3 40 5 < 1

Lymphopenia 89 41 7 81 24 3

Key: D=Daratumumab, Vd=bortezomib-dexamethasone.

Combination Treatment with Pomalidomide

Adverse reactions described in Table 8 reflect exposure to DARZALEX, pomalidomide and

dexamethasone (DPd) for a median treatment duration of 6 months (range: 0.03 to 16.9 months)

in Study 5. The most frequent adverse reactions (>20%) were infusion reactions, diarrhea,

constipation, nausea, vomiting, fatigue, pyrexia, upper respiratory tract infection, muscle spasms,

back pain, arthralgia, dizziness, insomnia, cough and dyspnea. The overall incidence of serious

(30)

adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included

pneumonia (7%). Adverse reactions resulted in discontinuations for 13% of patients.

Table 8: Adverse reactions with incidence ≥10% reported in Study 5 Body System

Adverse Reaction Any Grade (%) DPd (N=103)Grade 3 (%) Grade 4 (%)

Infusion reactionsa ₅₀ ₄ ₀ Gastrointestinal disorders Diarrhea 38 3 0 Constipation 33 0 0 Nausea 30 0 0 Vomiting 21 2 0

Fatigue 50 10 0

Pyrexia 25 1 0

Chills 20 0 0

Edema peripheralb ₁₇ ₄ ₀

Asthenia 15 0 0

Non-cardiac chest pain 15 0 0

Pain 11 0 0

Infections and infestations

Upper respiratory tract infectionc ₅₀ ₄ ₁

Pneumoniad ₁₅ ₈ ₂

Metabolism and nutrition disorders

Hypokalemia 16 3 0

Hyperglycemia 13 5 1

Decreased appetite 11 0 0

Musculoskeletal and connective tissue disorders

Muscle spasms 26 1 0

Back pain 25 6 0

Arthralgia 22 2 0

Pain in extremity 15 0 0

Bone pain 13 4 0

Musculoskeletal chest pain 13 2 0

Nervous system disorders

Dizziness 21 2 0 Tremor 19 3 0 Headache 17 0 0 Psychiatric disorders Insomnia 23 2 0 Anxiety 13 0 0

(31)

Table 8: Adverse reactions with incidence ≥10% reported in Study 5 Respiratory, thoracic and mediastinal disorders

Coughe ₄₃ ₁ ₀

Dyspneaf ₃₃ ₆ ₁

Nasal congestion 16 0 0

Key: D=Daratumumab, Pd=pomalidomide-dexamethasone.

a _{Infusion reaction includes terms determined by investigators to be related to infusion, see description of Infusion Reactions}

below.

b _{edema, edema peripheral, peripheral swelling.}

c _{acute tonsillitis, bronchitis, laryngitis, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, sinusitis,}

tonsillitis, upper respiratory tract infection

d _{lung infection, pneumonia, pneumonia aspiration} e _{cough, productive cough, allergic cough} f _{dyspnea, dyspnea exertional}

Laboratory abnormalities worsening during treatment are listed in Table 9.

Table 9: Treatment-emergent hematology laboratory abnormalities in Study 5 DPd (N=103) %

Any Grade Grade 3 Grade 4

Anemia 57 30 0

Thrombocytopenia 75 10 10

Neutropenia 95 36 46

Lymphopenia 94 45 26

Key: D=Daratumumab, Pd=pomalidomide-dexamethasone.