How To Manage Toxicities of New Hematological Agents

Amber Thomassen MA MSN AGNP-BC AOCNP

University of Miami Sylvester Comprehensive Cancer Center

Miami Florida

Disclosures

None

Objectives

bull Review the mechanism of action (MOA) in novel therapies for hematological malignancies

bull Review unique complicationstoxicities of novel therapies

bull Identify which toxicity a patient is experiencing and how to acttreat

Targeted Therapies

bull Treatment focus has shifted from standard cytotoxic regimens to more targeted approach over the past several decades

bull Targeted therapies work by interfering with molecules that promote cancer growth progression and spreading-cytostatic vs cytotoxic

bull AKA ldquomolecular therapyrdquo or ldquoprecision therapyrdquo

Types of Targeted Therapies

Immunotherapy

Signal Transduction Inhibitors

Apoptosis Inducers

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Disclosures

None

Objectives

bull Review the mechanism of action (MOA) in novel therapies for hematological malignancies

bull Review unique complicationstoxicities of novel therapies

bull Identify which toxicity a patient is experiencing and how to acttreat

Targeted Therapies

bull Treatment focus has shifted from standard cytotoxic regimens to more targeted approach over the past several decades

bull Targeted therapies work by interfering with molecules that promote cancer growth progression and spreading-cytostatic vs cytotoxic

bull AKA ldquomolecular therapyrdquo or ldquoprecision therapyrdquo

Types of Targeted Therapies

Immunotherapy

Signal Transduction Inhibitors

Apoptosis Inducers

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Objectives

bull Review the mechanism of action (MOA) in novel therapies for hematological malignancies

bull Review unique complicationstoxicities of novel therapies

bull Identify which toxicity a patient is experiencing and how to acttreat

Targeted Therapies

bull Treatment focus has shifted from standard cytotoxic regimens to more targeted approach over the past several decades

bull Targeted therapies work by interfering with molecules that promote cancer growth progression and spreading-cytostatic vs cytotoxic

bull AKA ldquomolecular therapyrdquo or ldquoprecision therapyrdquo

Types of Targeted Therapies

Immunotherapy

Signal Transduction Inhibitors

Apoptosis Inducers

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Targeted Therapies

bull Treatment focus has shifted from standard cytotoxic regimens to more targeted approach over the past several decades

bull Targeted therapies work by interfering with molecules that promote cancer growth progression and spreading-cytostatic vs cytotoxic

bull AKA ldquomolecular therapyrdquo or ldquoprecision therapyrdquo

Types of Targeted Therapies

Immunotherapy

Signal Transduction Inhibitors

Apoptosis Inducers

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Types of Targeted Therapies

Immunotherapy

Signal Transduction Inhibitors

Apoptosis Inducers

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Unique Treatment=Unique Toxicities

bull Traditionally less toxic than standard chemotherapy however can be just as serious

bull Commonly cause GI upset (diarrhea) hepatitis (increased liver enzymes) skin irritation (rash dry skin nailhair changes)

bull More serious toxicities may occur and some are more common with specific therapieshellip

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4

weeks with chemo and a checkpoint inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

VenetoclaxVenclexta

bull Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis

bull Orally bioavailable selective small molecule inhibitor of the anti-apoptotic protein Bcl-2 also has potential antineoplastic activity

bull Venetoclax mimics the native ligands of Bcl-2 and apoptosis activators thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Indications

bull For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion who have received at least one prior therapy

bull In combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Toxicities

PubChem 2019 Compound summary venetoclax retrieved httpspubchemncbinlmnihgovcompoundabt-199section

Common Toxicities gt30 of Patients

Leukopenia

Neutropenia

Diarrhea

Nausea

Common Toxicities 10-29 of Patients

Anemia Hyperphosphatemia

Thrombocytopenia Back pain

URI Swelling

Fatigue Cough

Hyperkalemia Hypokalemia

Vomiting Constipation

Headache

Serious Toxicity lt10 of Patients

bull Tumor Lysis Syndrome there is a risk for TLS at initiation and during the ramp-up phase

bull Patients should be assessed for TLS risk-evaluation of tumor burden-comorbidities-renal function-ppx

PubChem 2019 Compound summary venetoclax retrieved from httpspubchemncbinlmnihgovcompoundabt-199section

Treatment of TLS

bull lab changes can occur within 6-8 h post dose esp in initial dose and ramp up dosing HyperK Hyperphos hyperuricemia hypocalcemia

bull TLS ppx IV hydration anti-hyperuricemics (allopurinol) frequent monitoring of CMP

bull Treatment aggressive IVF correction of electrolyte imbalances-

bull Urinary alkalinization mdash The role of urinary alkalinization with either acetazolimide andor sodium bicarbonate is unclear and controversial

bull Rasburicase-is well tolerated rapidly breaks down serum uric acid and is effective in preventing and treating hyperuricemia and TLS

bull severe-gtdialysis

bull Larson and Pui (2019) Tumor lysis syndrome prevention and treatment Up to Date Retrieved from httpswwwuptodatecomcontentstumor-lysis-syndrome prevention-and-treatment

BlinatumomabBlincyto

bull Immunotherapy- bispecific CD19-directed CD3 T-cell engagerBiTEantibody

bull The drug acts as a connector between CD19 which is found on the surface of most B-cell lymphoblasts and CD3

Amgen (2017) blincyto-blinatumomab-significantly-improved-overall-survival-in-patients-with-bcell-precursor-acute- lymphoblastic-leukemia-compared-to-chemotherapy Retrieved from httpswwwamgencommedianews-releases201703

Indications

bull For the treatment of B-cell acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 01

bull Relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)

Amgen (2017) blincyto-blinatumomab-significantly-improved-overall-survival-in-patients-with-bcell-precursor-acute- lymphoblastic-leukemia-compared-to-chemotherapy Retrieved from httpswwwamgencommedianews-releases201703

Toxicities

Amgen (2017) blincyto-blinatumomab-significantly-improved-overall-survival-in-patients-with-bcell-precursor-acutelymphoblastic-leukemia-compared-to-chemotherapy Retrieved from httpswwwamgencommedianews-releases201703

Common Toxicities gt30 of Patients

Fever

Neurotoxicity

Headache

Infection

Less Common Toxicities 10-29 of Patients

leukopenia Fatigue Bone pain

Nausea DyspneaChest Pain

Dizziness

Rash Thrombocytopenia Insomnia

Diarrhea Cough Hyperglycemia

Hypomagnesemia

Hypokalemia Abdominal pain

Tremor Constipation Hypotension

Chills Anemia Anorexia

Neurotoxicity

bull In patients with ALL receiving blinatumomab in clinical studies neurological toxicities have occurred in approximately 65 of patients

bull The most common (ge 10) manifestations of neurological toxicity were headache and tremor

bull Grade 3 or higher (severe life-threatening or fatal) neurological toxicities following initiation of medication administration occurred in approximately 13 of patients and included encephalopathy convulsions speech disorders disturbances in consciousness confusion and disorientation and coordination and balance disorders

bull Monitor patients receiving blinatumomab for signs and symptoms of neurological toxicities Advise outpatients to contact their healthcare professional if they develop signs or symptoms of neurological toxicities

Amgen (2017) blincyto-blinatumomab-significantly-improved-overall-survival-in-patients-with-bcell-precursor-acute-lymphoblastic-leukemia-compared-to-chemotherapy Retrieved from httpswwwamgencommedianews-releases201703

Serious ToxicityCytokine Release Syndrome (CRS)

bull Cytokine Release Syndrome (CRS) which may be life-threatening or fatal has occurred in patients receiving blinatumomab

bull Manifestations of CRS include

-fever

-headache

-nausea

-asthenia

-hypotension

-elevated LFTs

-increased total bilirubin

-disseminated intravascular coagulation (DIC)

Goodman A (2015) Managing cytokine release syndrome The Oncology Nurse Sep (8) 164

LeRq Li Yuan Shord Nie Habtemariam Przepiorka Farrell Pazdur (2018) FDA approval summary Tocilizumab for treatment of chimeric antigen receptor T cell induced severe or life threatening cytokine release syndrome Oncologist Aug 2018

Cytokine Release Syndrome (CRS)Treatment

bull Median time to onset 2 days after start of infusion

bull cytokines are cell-signaling molecules that aid cell to cell communication and immune response

bull cytokine release syndrome or CRS is an uncontrolled inflammatory response ranging from symptoms that are very mild to severe cases and the most severe can lead to death

bull G1-supportive measures (IVFtylenol)

bull G2 boluses

bull G3-4 O2intubationpressorstoci given Q6h x 3 doses

bull G3 Withhold BLINCYTO until resolved then restart BLINCYTO at 9 mcgday Escalate to 28 mcgday after 7 days if the toxicity does not recur

bull G4- DC altogether

ObinutuzumabGazyva

bull Engineered Anti-CD20 monoclonal antibody

bull The drug binds to the CD20 antigen on the cancer cells and also to the immune effector cell triggering destruction of the CD20 bound cell

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

Cytokine Release Syndrome (CRS)Treatment

bull Median time to onset 2 days after start of infusion

bull cytokines are cell-signaling molecules that aid cell to cell communication and immune response

bull cytokine release syndrome or CRS is an uncontrolled inflammatory response ranging from symptoms that are very mild to severe cases and the most severe can lead to death

bull G1-supportive measures (IVFtylenol)

bull G2 boluses

bull G3-4 O2intubationpressorstoci given Q6h x 3 doses

bull G3 Withhold BLINCYTO until resolved then restart BLINCYTO at 9 mcgday Escalate to 28 mcgday after 7 days if the toxicity does not recur

bull G4- DC altogether

ObinutuzumabGazyva

bull Engineered Anti-CD20 monoclonal antibody

bull The drug binds to the CD20 antigen on the cancer cells and also to the immune effector cell triggering destruction of the CD20 bound cell

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

ObinutuzumabGazyva

bull Engineered Anti-CD20 monoclonal antibody

bull The drug binds to the CD20 antigen on the cancer cells and also to the immune effector cell triggering destruction of the CD20 bound cell

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

Indications

bull In combination with chemotherapy followed by monotherapy in patients achieving at least a partial remission is indicated for the treatment of adult patients with previously untreated stage II bulky III or IV follicular lymphoma (FL)

bull In combination with bendamustine followed by monotherapy is indicated for the treatment of patients with follicular lymphoma (FL) who relapsed after or are refractory to a rituximab-containing regimen

bull In combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL)

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

Toxicities

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

Common Toxicities gt30 of Patients

Lymphocytopenia

Leukopenia

Neutropenia

Initial Infusion Reaction

Infection

Hypoglycemia

Hyperkalemia

Less Common Toxicities 10-29 of Patients

Hyponatremia Elevated ASTALT

Hypoalbuminemia

Anemia

Hypokalemia Elevated creatinine

Serious Rare Toxicities

bull Progressive Multifocal Leukoencephalopathy (PML)-damage to myelin

-symptoms include general weakness sensory loss vision changes facial drooping

bull Hepatitis B virus reactivation (only in those with previous HBV infections)

bull Late-onset hypersensitivity diagnosed as serum sickness has also been reported

-symptoms include chest pain diffuse arthralgia and fever

bull Tumor Lysis Syndrome-assess patients for risk of TLS prior to administration

Gazyva prescribing information Retrieved from httpswwwgazyvacomhcpflflhtml

Anti-PD1 ldquoCheckpoint Inhibitorsrdquo

bull What is PD1 -A protein found on T cells that helps keep the bodys immune responses in check When PD-1 is bound to another protein called PD-L1 it helps keep T cells from killing other cells including cancer cells

bull Sohellipwhat does an anti-PD1 drug do

-Drugs that target PD-1 block the binding of PD1 to PD-L1 allowing the immune system to respond and kill the cancer cells (Takes the breaks off of the immune system)

bull Examples Nivolomab (Opdivo) Pembrolizumab (Keytruda) Cemiplimab (Libtayo)

httpswwwcancerorgtreatmenttreatments-andimmune-checkpoint-inhibitorshtml

httpswwwcancergovpublicationsdictionariescancer-termsdefpd-1

Indications

bull Anti-PD1 have been approved in many solid tumors such as

-stomach

-lung

-bladder

-cervical

- colorectal

-head and neck and other cancers

Also used in the treatment of cHL

National Cancer Institute 2019 Targeted therapies fact sheet retrieved from httpswwwcancergovabout-cancertreatmenttypestargeted-therapiestargeted-therapies-fact-sheet

Meti Esfahani and Johnson (2018) The role of immune checkpoint inhibitors in classical Hodgkinrsquos lymphoma Cancers

Toxicities

bull One concern with this type of drug is that sometimes the immune system attacks organs in the body which can lead to serious side effects in some people such as

-Pneumonitis

-Colitis

-Hepatitis

National Cancer Institute 2019 Targeted therapies fact sheet retrieved from httpswwwcancergovabout-cancertreatmenttypestargeted-therapiestargeted-therapies-fact-sheet

Common Toxicities gt30 of Patients

Fatigue Cough

Nausea Anorexia

Rash Pruritus

Mr Cbull 77 year old male with newly diagnosed AML No acute complaints

-BMBX reveals 87 blasts

-Pre- treatment Labs -6 hr post-tx -8 hr post-txNa 147

K 36

Creat 095

Ca 79

Total Bili 04

AST 28

ALT 10

LDH 753

Phos 51

Uric Acid

79

WBC 119

Hbg 78

Plt 23

ANC 155

Blast 20

Na 143

K 86

Creat 104

Ca 77

Total Bili 02

AST 96

ALT 13

LDH gt2500

Phos 119

Uric Acid

142

Na 143

K 80

Creat 104

Ca 74

Total Bili 02

AST 133

ALT 13

LDH gt2500

Phos 150

Uric Acid

151

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

CARTOX 10

Orientation to year month city hospital and President Total of 5 points

(one point for each)-gt5

Name three objects for example point to clock pen button Total of 3

points

(one point for each)-gt 3

Write a standard sentence eg lsquothe sky is blue 1 point-gt 1

Count backwards from 100 in tens 1 point-gt 1

Total score 10-gt No neurotoxicities noted

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4 weeks with chemo and a checkpoint

inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

-Gather more informationhellip

-What is his baseline of stoolsday

1

-How many times has he had diarrheaday

6

-How many days has this been going on

5

-Has he tried anything to help at home (foodsOTC remedies etc)

no

-Any other symptoms (feverchillsnauseavomiting)

no

-Rule out infectious process (C-Diff)

Send stool samplelabsvitals

Thank you

Mrs Zbull 47 year old female with relapsed ALL Admitted for her first infusionbull Pre-treatment Post-treatment (6 hours)

no acute complaints Patient co nausea chills headache

physical exam unremarkableneuro-status normal PE tachycardic visible rigors neuro-status normal

Na 140

K 38

Creat 093

Ca 81

Total Bili 04

AST 32

ALT 12

LDH 523

Phos 40

Uric Acid 42

WBC 22

Hbg 78

Plt 44

ANC 655

HR 77

RR 18

BP 12887

Temp 988371

HR 102

RR 20

BP 10057

Temp 1014385

CARTOX 10

Orientation to year month city hospital and President Total of 5 points

(one point for each)-gt5

Name three objects for example point to clock pen button Total of 3

points

(one point for each)-gt 3

Write a standard sentence eg lsquothe sky is blue 1 point-gt 1

Count backwards from 100 in tens 1 point-gt 1

Total score 10-gt No neurotoxicities noted

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4 weeks with chemo and a checkpoint

inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

-Gather more informationhellip

-What is his baseline of stoolsday

1

-How many times has he had diarrheaday

6

-How many days has this been going on

5

-Has he tried anything to help at home (foodsOTC remedies etc)

no

-Any other symptoms (feverchillsnauseavomiting)

no

-Rule out infectious process (C-Diff)

Send stool samplelabsvitals

Thank you

Mr Fbull Mr F is a 60 year old male diagnosed with cHL He has been on treatment for 4 weeks with chemo and a checkpoint

inhibitor He comes to clinic reporting new onset of diarrhea

bull What do we do

-Gather more informationhellip

-What is his baseline of stoolsday

1

-How many times has he had diarrheaday

6

-How many days has this been going on

5

-Has he tried anything to help at home (foodsOTC remedies etc)

no

-Any other symptoms (feverchillsnauseavomiting)

no

-Rule out infectious process (C-Diff)

Send stool samplelabsvitals

Thank you

Thank you