diff --git a/.yarn/cache/@babel-runtime-npm-7.15.4-52ce5bf6ea-c408254304.zip b/.yarn/cache/@babel-runtime-npm-7.15.4-52ce5bf6ea-c408254304.zip
new file mode 100644
index 000000000000..b8f81418e26f
Binary files /dev/null and b/.yarn/cache/@babel-runtime-npm-7.15.4-52ce5bf6ea-c408254304.zip differ
diff --git a/.yarn/cache/downshift-npm-5.2.1-21b424890b-fc8e731106.zip b/.yarn/cache/downshift-npm-5.2.1-21b424890b-fc8e731106.zip
deleted file mode 100644
index cfd594887684..000000000000
Binary files a/.yarn/cache/downshift-npm-5.2.1-21b424890b-fc8e731106.zip and /dev/null differ
diff --git a/.yarn/cache/downshift-npm-6.1.7-22c05c4fb9-0904ed8f28.zip b/.yarn/cache/downshift-npm-6.1.7-22c05c4fb9-0904ed8f28.zip
new file mode 100644
index 000000000000..45af17447ccb
Binary files /dev/null and b/.yarn/cache/downshift-npm-6.1.7-22c05c4fb9-0904ed8f28.zip differ
diff --git a/.yarn/cache/tslib-npm-2.3.1-0e21e18015-de17a98d46.zip b/.yarn/cache/tslib-npm-2.3.1-0e21e18015-de17a98d46.zip
new file mode 100644
index 000000000000..f2a05ef439aa
Binary files /dev/null and b/.yarn/cache/tslib-npm-2.3.1-0e21e18015-de17a98d46.zip differ
diff --git a/packages/react/package.json b/packages/react/package.json
index f416f3581c60..8d6cd689c00a 100644
--- a/packages/react/package.json
+++ b/packages/react/package.json
@@ -50,7 +50,7 @@
     "@carbon/telemetry": "0.0.0-alpha.6",
     "classnames": "2.3.1",
     "copy-to-clipboard": "^3.3.1",
-    "downshift": "5.2.1",
+    "downshift": "6.1.7",
     "flatpickr": "4.6.9",
     "invariant": "^2.2.3",
     "lodash.debounce": "^4.0.8",
diff --git a/packages/react/src/components/MultiSelect/MultiSelect.js b/packages/react/src/components/MultiSelect/MultiSelect.js
index 392bc95476c3..aa148aa2cb46 100644
--- a/packages/react/src/components/MultiSelect/MultiSelect.js
+++ b/packages/react/src/components/MultiSelect/MultiSelect.js
@@ -190,6 +190,9 @@ const MultiSelect = React.forwardRef(function MultiSelect(
       case ItemClick:
       case MenuKeyDownSpaceButton:
       case MenuKeyDownEnter:
+        if (changes.selectedItem === undefined) {
+          break;
+        }
         onItemChange(changes.selectedItem);
         break;
       case MenuKeyDownArrowDown:
diff --git a/yarn.lock b/yarn.lock
index 788d7a0d0e5a..57d0dadaa03c 100644
--- a/yarn.lock
+++ b/yarn.lock
@@ -1620,7 +1620,7 @@ __metadata:
   languageName: node
   linkType: hard
 
-"@babel/runtime@npm:^7.0.0, @babel/runtime@npm:^7.1.2, @babel/runtime@npm:^7.10.2, @babel/runtime@npm:^7.11.2, @babel/runtime@npm:^7.12.5, @babel/runtime@npm:^7.13.10, @babel/runtime@npm:^7.13.17, @babel/runtime@npm:^7.13.8, @babel/runtime@npm:^7.14.6, @babel/runtime@npm:^7.3.1, @babel/runtime@npm:^7.4.4, @babel/runtime@npm:^7.5.0, @babel/runtime@npm:^7.5.5, @babel/runtime@npm:^7.7.2, @babel/runtime@npm:^7.7.4, @babel/runtime@npm:^7.7.6, @babel/runtime@npm:^7.8.4, @babel/runtime@npm:^7.8.7, @babel/runtime@npm:^7.9.1, @babel/runtime@npm:^7.9.2":
+"@babel/runtime@npm:^7.0.0, @babel/runtime@npm:^7.1.2, @babel/runtime@npm:^7.10.2, @babel/runtime@npm:^7.11.2, @babel/runtime@npm:^7.12.5, @babel/runtime@npm:^7.13.10, @babel/runtime@npm:^7.13.17, @babel/runtime@npm:^7.13.8, @babel/runtime@npm:^7.14.6, @babel/runtime@npm:^7.3.1, @babel/runtime@npm:^7.4.4, @babel/runtime@npm:^7.5.0, @babel/runtime@npm:^7.5.5, @babel/runtime@npm:^7.7.2, @babel/runtime@npm:^7.7.4, @babel/runtime@npm:^7.7.6, @babel/runtime@npm:^7.8.4, @babel/runtime@npm:^7.8.7, @babel/runtime@npm:^7.9.2":
   version: 7.14.6
   resolution: "@babel/runtime@npm:7.14.6"
   dependencies:
@@ -1629,6 +1629,15 @@ __metadata:
   languageName: node
   linkType: hard
 
+"@babel/runtime@npm:^7.14.8":
+  version: 7.15.4
+  resolution: "@babel/runtime@npm:7.15.4"
+  dependencies:
+    regenerator-runtime: ^0.13.4
+  checksum: c40825430400e47c19b97e4142d5315d2910305b9714d44a711472587ee2fd4521fdba5f02ddd9df3902f5e988d9854fa83f4da1e0c091f70f6983fa52480606
+  languageName: node
+  linkType: hard
+
 "@babel/template@npm:^7.12.7, @babel/template@npm:^7.14.5, @babel/template@npm:^7.3.3":
   version: 7.14.5
   resolution: "@babel/template@npm:7.14.5"
@@ -10347,7 +10356,7 @@ __metadata:
     css-loader: ^3.4.2
     cypress: ^8.1.0
     cypress-real-events: ^1.5.1
-    downshift: 5.2.1
+    downshift: 6.1.7
     fast-sass-loader: ^1.5.0
     flatpickr: 4.6.9
     gzip-size: ^6.0.0
@@ -11678,7 +11687,7 @@ __metadata:
   languageName: node
   linkType: hard
 
-"compute-scroll-into-view@npm:^1.0.13, compute-scroll-into-view@npm:^1.0.17":
+"compute-scroll-into-view@npm:^1.0.17":
   version: 1.0.17
   resolution: "compute-scroll-into-view@npm:1.0.17"
   checksum: b20c05a10c37813c5a6e4bf053c00f65c88d23afed7a6bd7a2a69e05e2ffc2df3483ecfe407d36bf16b8cec8be21ae1966c9c523093a03117e567156cd79a51e
@@ -13690,17 +13699,18 @@ __metadata:
   languageName: node
   linkType: hard
 
-"downshift@npm:5.2.1":
-  version: 5.2.1
-  resolution: "downshift@npm:5.2.1"
+"downshift@npm:6.1.7":
+  version: 6.1.7
+  resolution: "downshift@npm:6.1.7"
   dependencies:
-    "@babel/runtime": ^7.9.1
-    compute-scroll-into-view: ^1.0.13
+    "@babel/runtime": ^7.14.8
+    compute-scroll-into-view: ^1.0.17
     prop-types: ^15.7.2
-    react-is: ^16.13.1
+    react-is: ^17.0.2
+    tslib: ^2.3.0
   peerDependencies:
-    react: ">=0.14.9"
-  checksum: fc8e731106cdaa9bfcd1d855d8b25dbaaa6fb22dfb51a3c32e51f460c199730a6ddfbd311891bbdc4bba642238d2239f1fb7642ce5d3f616f09fc68abd6a76f4
+    react: ">=16.12.0"
+  checksum: 0904ed8f285d31ee00e471dcddd57e72468bee354b191167bcaebe690ec292647fe4c31f483665094d750e72dd71e5d7db695acef33ab5dba6a39fed0112bab6
   languageName: node
   linkType: hard
 
@@ -33191,6 +33201,13 @@ resolve@^2.0.0-next.3:
   languageName: node
   linkType: hard
 
+"tslib@npm:^2.3.0":
+  version: 2.3.1
+  resolution: "tslib@npm:2.3.1"
+  checksum: de17a98d4614481f7fcb5cd53ffc1aaf8654313be0291e1bfaee4b4bb31a20494b7d218ff2e15017883e8ea9626599b3b0e0229c18383ba9dce89da2adf15cb9
+  languageName: node
+  linkType: hard
+
 "tsutils@npm:^3.21.0":
   version: 3.21.0
   resolution: "tsutils@npm:3.21.0"