Understanding Corneal Events Associated With mafodotin ... · 8/6/2020 · Corbelli E, et al....

Non-Promotional Scientific Discussion Use

Understanding Corneal

Events Associated With

BLENREP (belantamab

mafodotin-blmf):

Guide for Eye Care

Professionals

Version 1.0Updated August 6, 2020 -

please check this link for the

most updated version

https://d201nm4szfwn7c.cloudfront.net/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/373434da-68c2-4171-ac61-5a89ea3b20ca/373434da-68c2-4171-ac61-5a89ea3b20ca_viewable_rendition__v.pdf

Non-Promotional Scientific Discussion Use

Multiple myeloma1 BLENREP indicationand usage

5

BLENREP-associatedcorneal adverse events

7

Antibody-drug conjugatesfor cancer

2

Other antibody-drugconjugates associated with corneal adverse events

4

BLENREP – a BCMA-targeting antibody-drug conjugate

3

DREAMM-2 study design6

Patient monitoring –ophthalmic exams

9

Patient monitoring and management by eyecare professionals

8

TABLE of

CONTENTS

How to gradecorneal adverse eventsand communicate tohematologist/oncologist

10

Patient resources11

BLENREP resources for eye care professionals

12

3Non-Promotional Scientific Discussion Use

Multiple Myeloma (MM) Is an Incurable Hematologic Cancer

1. Palumbo A, et al. N Engl J Med 2011;364:1046–60; 2. Neri P, et al. Clin Cancer Res 2016;22:5959–65; 3. Kaufman JL, et al. Blood Cancer J 2019;9:3; 4. National Cancer Institute. https://seer.cancer.gov/statfacts/html/mulmy.html. [Accessed May 2020]; 5. Mikhael J. Clin Lymphoma Myeloma Leuk 2020;20:1–17; 6. Chari A, et al. N Engl J Med 2019;381:727–38; 7. Gandhi UH, et al. Leukemia 2019;33:2266–75; 8. Pick M, et al. Eur J Haematol 2018;100:494–501.

Multiple myeloma is an incurable hematologic cancer characterized by

accumulation of malignant plasma cells in the bone marrow1–3

MM accounts for

of all new cancer

cases in the

United States4

Therefore,

novel therapies

are needed for

patients who

have exhausted

available

treatment

options5

The median age

at diagnosis is

69 years4Current standard-of-care treatment

options include immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies5

Patients refractory to agents in all three of these classes have an especially

poor prognosis5–8

• In recent studies, the median overall survival for these patients

was <10 months6,7

• With each subsequent therapy, the likelihood of response and

length of survival decrease7

~2%


BLENREP for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

REMS, risk evaluation and mitigation strategy. Prescribing Information for BLENREP.

• BLENREP is a B-cell maturation antigen (BCMA)–directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent

• This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s)

• This is not inclusive of all potential adverse events; please refer to the full Prescribing Information for BLENREP for complete safety information

WARNING: OCULAR TOXICITY

• BLENREP caused changes in the corneal epithelium resulting in changes in vision, including severe

vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes.

• Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms.

Withhold BLENREP until improvement and resume, or permanently discontinue, based on severity.

• Because of the risk of ocular toxicity, BLENREP is available only through a restricted program under a

Risk Evaluation and Mitigation Strategy (REMS) called the BLENREP REMS.

https://gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF


Monoclonal antibody

ADCs leverage the ability to

specifically target cells with a

monoclonal antibody directed

against proteins expressed on

the surface

of cells1

Antibody-Drug Conjugates (ADCs) Represent a Newer Class of BCMA-Targeting Therapies

1. Shim H. Biomolecules 2020;10:360; 2.ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?cond=&term=antibody+drug+conjugate&cntry=&state=&city=&dist [Accessed June 25, 2020].

Currently 7 ADCs approved for oncology indications and

>100 clinical trials of ADCs across tumor types1,2

Linker

A stable linker joins the

cytotoxic drug to the

monoclonal antibody1

ADCs are internalized into

cells; inside the lysosome,

linkers are degraded1

Thus, in principle, the

cytotoxic drug is only

actively released inside

cancer cells1

Cytotoxic drug

A cytotoxic drug or “payload” is

attached to the monoclonal

antibody, providing potent

cell-killing activity1


BLENREP Is an Antibody-Drug Conjugate Targeting BCMA

IgG1, immunoglobulin G1; mAb, monoclonal antibody; MMAF, monomethyl auristatin F.1. O’Connor BP, et al. J Exp Med 2004;199:91–8; 2. Lee L, et al. Br J Haematol 2016;174:911–22; 3. Tai Y-T, et al. Blood 2014;123:3128–38.

The target

The agent

B-cell maturation antigen (BCMA) is a protein expressed on normal B lymphocytes and multiple myeloma cells

that promotes cellular proliferation and survival1,2

BLENREP is a BCMA-directed antibody and microtubule inhibitor conjugate, composed of three components3:

1

2

3

Afucosylated, humanized IgG1 anti-BCMA mAb

MMAF, a microtubule inhibitor

Protease-resistant maleimidocaproyl linker joining

MMAF and the mAb


BLENREP Mechanism of Action

.ADC, antibody-drug conjugate; ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; BCMA, B-cell maturation antigen; Fc, fragment crystallizable; mAb, monoclonal antibody; MM, multiple myeloma; MMAF, monomethyl auristatin F.Prescribing Information for BLENREP. Image adapted from Richardson P, et al. Presented at the 61st Annual Meeting of the American Scoiety of Hematology, December 7–10, 2019, Orlando, FL. Poster 1857.

Mechanism

of action

1BLENREP binds to BCMA expressed on

normal and malignant plasma cells

2BLENREP is internalized and MMAF is

released following proteolytic cleavage

from the mAb

3

MMAF intracellularly disrupts the

microtubule network, leading to cell cycle

arrest and apoptosis

BLENREP was also shown to induce

tumor cell lysis via ADCC and ADCP

BCMA

BCMA

BCMA BCMA

Lysosome

ADC

Fc

Receptor

ADCC/ADCP

Effector

Cell

Malignant

Plasma Cell

Cell death BLENREP may

also target normal

plasma cells


Antibody-Drug Conjugates Containing MMAF Are Associated With Corneal Adverse Events

ADC, antibody-drug conjugate; BCMA, B-cell maturation antigen; mAb, monoclonal antibody; MMAF, monomethyl auristatin F.1. Trudel S, et al. Blood Cancer J 2019;9:37; 2. Eaton JS, et al. J Ocul Pharmacol Ther 2015;31:589–604; 3. Zhao H, et al. Cancer Res 2018;78:2115–26; 4. Younes A, et al. J Clin Oncol 2012;30:2776–82; 5. Deklerck E, et al. Breast Cancer Res Treat 2019;175:525–30; 6. Tannir NM, et al. Invest New Drugs 2014;32:1246–57; 7. Lee BA, et al. Cornea 2018 [RETRACTED]; 8. Corbelli E, et al. Cornea 2019;38:229–32; 9. Farooq A, et al. Ophthalmol Ther 2020 Jul 25. doi: 10.1007/s40123-020-00280-8.

1Ocular surface adverse events observed with ADCs were described as multiple, bilateral, microcyst-like lesions in the

superficial cornea starting in the periphery and migrating centrally toward the pupil4–8

2Corneal adverse events may be related to the nonspecific uptake of the ADC into rapidly-dividing corneal cells, which causes

apoptosis and produces visible corneal microcysts9

Corneal adverse events, such as blurred vision, keratitis, dry eyes, photophobia, or

microcystic epithelial findings, have been reported with various ADCs in development

which utilize the microtubule-disrupting agent MMAF1–3

Anti-BCMA mAb BLENREPNoncleavable

Linker

N

O

OO

MMAF Toxin

N

O

H

N

O

N

OOCH3 OCH3

N

O

N

H O

OH


DREAMM-2 Study Design

3L+, third line plus; ADA, antidrug antibodies; CBR, clinical benefit rate; DOR, duration of response; HRQOL, health-related quality of life; IRC, independent review committee; IV, intravenous; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PRO, patient-reported outcome; Q3W, every 3 weeks; RRMM, relapsed/refractory multiple myeloma; TTP, time to progression; TTR, time to response. *Screening occurred between June 18, 2018, and January 2, 2019; †DREAMM-2 was not designed to compare the two doses; ‡presence or absence of t(4;14), t(14;16), or del(17p13) per the study protocol. 1q21+ was included in the analysis.Lonial S, et al. Lancet Oncol 2020;21:207–21.

A Phase II, open-label, randomized, two-dose study in patients with RRMM who were

refractory to an immunomodulatory agent, proteasome inhibitor, and were refractory to/intolerant of an anti-CD38

monoclonal antibody

BLENREP

3.4 mg/kg IV (frozen) Q3W

n=99

RA

ND

OM

IZE

1:1

†BLENREP

2.5 mg/kg IV (frozen) Q3W

n=97

SC

RE

EN

ING

*

Patients:

3L+ RRMM

N=293

Stratified by prior

lines of therapy

(≤4 vs >4) and

high-risk

cytogenetic

featuresc

Additional cohort treated with

lyophilized configuration

n=25

PRIMARY OUTCOME

• ORR per IRC

Initial results from the ocular substudy suggest that corticosteroid eye drops were an

ineffective prophylaxis for the development of changes to the corneal epithelium

Monocular prophylactic

corticosteroid eyedrops at

3.4 mg/kg-dose level

n=13

Monocular prophylactic

corticosteroid eyedrops at

2.5 mg/kg-dose level

n=17

RA

ND

OM

IZE

1:1

Le

ft e

ye

: R

igh

t e

ye

Corticosteroid eyedrops given in

the allocated eye only

Artificial tears given instead of

corticosteroids in the control eye

Preservative-free artificial tears were

also administered 4–8x daily in

both eyes

Ocular substudy

OUTCOME

Description of differences in

corneal findings in each eye based

on ophthalmic examinations

(participant level)

Treatment until disease progression

or unacceptable toxicity

Rx


DREAMM-2: Comprehensive Assessments of Ocular Events

AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; KVA, Keratopathy and Visual Acuity.*Patients had to undergo routine ophthalmologic exams prior to every dose.Lonial S, et al. Lancet Oncol. 2020;21(2):207–221

• Collected and graded by investigator

using CTCAE

– Subjective symptoms of

blurred vision, dry eye, etc.

AEs as Reported

by Patients

Corneal Data Collection

• Graded by investigator based on predefined

criteria from the KVA scale

Corneal Exam

Findings*

Best-Corrected

Visual Acuity

Objective findings

informed dose modifications


Keratopathy Was the Most Common BLENREP-Associated Ocular Adverse Event in DREAMM-2

*Keratopathy was based on slit lamp eye examination, characterized as corneal epithelium changes with or without symptoms; †visual acuity changes were determined upon eye examination; ‡blurred vision included diplopia, vision blurred, visual acuity reduced, and visual impairment; §dry eyes included dry eye, ocular discomfort, and eye pruritus.Prescribing Information for BLENREP.

Eye disorders

BLENREP 2.5 mg/kg (n=95)

All grades

(%)

Grade 3–4

(%)

Keratopathy* 71 44

Decreased visual acuity† 53 28

Blurred vision‡ 22 4

Dry eyes§ 14 1

In DREAMM-2, ocular events were the most

commonly reported type of adverse events

The most common ocular adverse events

were keratopathy, decreased visual acuity,

blurred vision, and dry eyes

• Other clinically relevant eye disorders in <10% of patients included photophobia, eye irritation, infective

keratitis, and ulcerative keratitis


Keratopathy on Slit Lamp Eye Examination Was Characterized by Microcyst-Like Epithelial Changes in the Superficial Layer of the Cornea

MEC, microcyst-like epithelial change. Image courtesy of Dr. Shaohui Liu, Assistant Professor of Clinical Ophthalmology, Indiana University School of Medicine

Slit lamp microscopic

image of keratopathy

(MECs), depicted

by pink arrow


Progression and Resolution of MECs in the Epithelium

MEC, microcyst-like epithelial change.

Microcyst-like deposits larger for representation, not to scale. Schematic example


Slit Lamp Microscopic Images of Microcyst-Like Epithelial Changes

MEC, microcyst-like epithelial change.Farooq A, et al. Ophthalmol Ther 2020 Jul 25. doi: 10.1007/s40123-020-00280-8. .

• On slit lamp microscopy, MEC lesions were small and located within the corneal epithelium

• MECs (shown by arrowheads) are seen here in the corneal periphery and midperiphery

• Visualization requires high magnification and is aided by the use of retroillumination off the iris or indirect illumination

Reprinted by permission from Springer Nature: Springer. Ophthalmology and Therapy. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate

Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq AV, Esposti S, Popat R, et al. 2020, advance online publication, 25 July 2020. doi: 10.1007/s40123-020-00280-8.


Case Report From DREAMM-2: Slit Lamp and Confocal Images of Microcyst-Like Epithelial Changes

MEC, microcyst-like epithelial change.Farooq A, et al. Ophthalmol Ther 2020 Jul 25. doi: 10.1007/s40123-020-00280-8.

Slit lamp images of left (a) and right (b) eyes with arrows demonstrating MECs

Opacities were not visualized within the anterior stroma (f) or endothelium (not shown)

Opacities were noted to be most prominent in the wing cells (d) and basal cells (e), compared with the superficial cells (f)

Adapted by permission from Springer Nature: Springer. Ophthalmology and Therapy. Corneal Epithelial Findings in Patients with Multiple

Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq AV, Esposti S,

Popat R, et al. ©2020.

Adapted by permission from Springer Nature: Springer. Ophthalmology and Therapy. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab

Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq AV, Esposti S, Popat R, et al. ©2020.

In vivo confocal images of the same patient (c–f) demonstrating hyperreflective opacities within the corneal epithelium


Objective Corneal Exam Findings by Maximum Grade in DREAMM-2

1. Data on File. Study 205678. GSK Study Register. Available at: https://www.gsk-studyregister.com; 2. Prescribing Information for BLENREP.

Grade Description

BLENREP 2.5 mg/kg1

(n=95)

n (%)

Pooled safety

population2

(n=218)

n (%)

Grade 1 Mild superficial keratopathy 8 (8) 16 (7)

Grade 2 Moderate superficial keratopathy 17 (18) 49 (22)

Grade 3 Severe superficial keratopathy 42 (44) 99 (45)

Grade 4 Corneal epithelial defect 0 1 (0.5)

Pooled safety population reflects exposure to BLENREP at a dose of 2.5 mg/kg or 3.4 mg/kg (1.4-times the recommended dose) administered intravenously

once every 3 weeks in 218 patients in DREAMM-2


Most Common Adverse Events Leading to Dose Delays and Reductions in DREAMM-2

Prescribing Information for BLENREP.

Preferred term (>3% of patients)

BLENREP 2.5 mg/kg

(n=95)

Dose delays

(%)

Dose reductions

(%)

Any patient 54 29

Keratopathy 47 23

Blurred vision 5 2

Pneumonia 3.2 0

Thrombocytopenia 0 5

Dry eye 3.2 0

• Though dose delays and reductions were common, 8% of patients discontinued due to adverse events

• The most frequent adverse event resulting in permanent discontinuation was keratopathy (2.1%)


Keratopathy Can Occur With or Without Symptoms

Data based on 13-month update. *Symptomatic = adverse event by preferred term or ≥2 lines of visual acuity change; †visual acuity change = 20/50 or worse in better-seeing eye.Data on File. Study 205678. GSK Study Register. Available at: https://www.gsk-studyregister.com.

Additional pooled safety data available in the US Prescribing Information

BLENREP 2.5 mg/kg

n=95

Keratopathy

68/95 (72%)

Symptomatic*

53/95 (56%)

Visual acuity

change†

17/95 (18%)

Discontinuation

due to corneal AE

3/95 (3%)

No new safety

signals observed at

13-month follow-up

82% of patients without

clinically significant

visual acuity change†

1 patient developed a

Grade 4 corneal ulcer


Recovery of Keratopathy

Patients with keratopathy

(Grade ≥2)

n=60

Median time to onset, days (range) 37 (19–143)

Recovered from first occurrence, n (%) 46 (77)

Recovered to Grade 1 or lower, n (%) 29 (48)

Median time to resolution, days (range) 81 (11–232)

Had ongoing keratopathy, n (%) 31 (52)

Still on treatment 9 (15)

In follow-up 5 (8)

Lost to follow-up/death* 17 (28)

Data based on 13-month update. *Median time from last dose to last exam = 23 days. Data on File. Study 205678. GSK Study Register. Available at: https://www.gsk-studyregister.com.

Keratopathy was based on slit lamp eye examination, characterized as corneal epithelium

changes with or without symptoms


Changes in Best-Corrected Visual Acuity

BCVA, best-corrected visual acuity. Bilateral BCVA-assessed vision changes in the better-seeing eye. Data based on 13-month update. Farooq A, et al. Ophthalmol Ther. 2020 Jul 25. doi: 10.1007/s40123-020-00280-8. Online ahead of print.

BLENREP 2.5 mg/kg

n=95

Bilateral BCVA

20/50 or worse

Bilateral BCVA

20/200 or worse

Patients, n (%) 17 (18) 1 (<1)

Median time to onset, days (range) 66 (20–442) 21 (21–21)

Median time to resolution, days (range) 22 (7–64) 22 (22–22)

Resolved as of last assessment, n (%) 14 (82) 1 (100)

Permanent vision loss was not reported


BLENREP Risk Evaluation and Mitigation Strategy (REMS)

What is the BLENREP REMS?

A REMS is a strategy to manage known or potential risks associated with a product. It is

required by the Food and Drug Administration to ensure the benefits of the drug

outweigh its risks

Due to the risk of ocular toxicity, BLENREP is only available through a restricted program

called the BLENREP REMS

Prescribers and heathcare site must be certified, and patients must be enrolled in the

BLENREP REMS and comply with REMS requirements

in order to receive BLENREP

For more information, please visit https://blenreprems.com/

https://blenreprems.com/


Eye Care Professionals Play an Integral Role in Managing PatientsReceiving BLENREP

Ophthalmic exams are critical not only for the mitigation and management of cornealadverse events, but also in enabling patients to receive each dose of treatment

As an eye care professional, you play an integral role in the

management of patients receiving BLENREP by:

Performing ophthalmic

exams before patients can

initiate treatment with

BLENREP

and prior to each

subsequent dose of

BLENREP

Grading corneal adverse

events observed during

ophthalmic exams

Communicating

exam findings/

corneal adverse events to

hematologist/oncologists

to inform potential

dose modifications

Advising patients on

appropriate supportive

care measures


OPHTHALMIC EXAMS (VISUAL ACUITY AND SLIT LAMP)

Before patients can receive treatment with BLENREP, a baseline ophthalmic

exam must be performed within 3 weeks prior to first dose

Patients Receiving BLENREP Require Monitoring By Eye Care Professionals


Exam

Baseline exam(prior to starting treatment)

• Patients must have an ophthalmic exam (visual acuity and slit lamp) before each dose of BLENREP, and promptly for worsening symptoms

o BLENREP is given as an intravenous infusion once every 3 weeks

o Perform each follow-up exam at least 1 week after the previous dose and within 2 weeks prior to the next dose

First dose Second dose Third dose Ongoing treatment

3 weeks

Exam Exam


Grading Corneal Adverse Events per the Keratopathy and Visual Acuity (KVA) Scale to Inform Dosing Decisions

BCVA, best-corrected visual acuity.


Corneal adverse event

(exam by eye care professional)

Recommended dose modifications

(Made by hematologist/oncologist)

Grade 1

Corneal examination finding(s):

Mild superficial keratopathya

Change in BCVAb:

Decline from baseline of 1 line on Snellen Visual Acuity

Continue treatment at current dose

Grade 2


Moderate superficial keratopathyc

Change in BCVAb:

Decline from baseline by 2 or 3 lines (and Snellen Visual Acuity not worse than 20/200)

Withhold BLENREP until improvement in both

corneal examination findings and change in

BCVA to Grade 1 or better and resume at

same dose

Grade 3


Severe superficial keratopathyd

Change in BCVAb:

Decline from baseline of more than 3 lines (and Snellen Visual Acuity not worse than 20/200)

Withhold BLENREP until improvement in both

corneal examination findings and change in

BCVA to Grade 1or better and resume at a

reduced dose

Grade 4


Corneal epithelial defecte

Change in BCVAb:

Snellen Visual Acuity worse than 20/200

Consider permanent discontinuation of

BLENREP. If continuing treatment, withhold

BLENREP until improvement in both corneal

examination findings and change in BCVA to

Grade 1 or better and resume at reduced dose.aMild superficial keratopathy (documented worsening from baseline), with or without symptoms; bchanges in visual acuity due to treatment-related corneal findings; cmoderate superficial keratopathy with or without patchy microcyst-like

deposits, sub-epithelial haze (peripheral), or a new peripheral stromal opacity; dsevere superficial keratopathy with or without diffuse microcyst-like deposits, sub-epithelial haze (central), or a new central stromal opacity; ecorneal epithelial

defect such as corneal ulcers.


Description of Corneal Examination Findings per KVA ScaleDescriptions from Table 1 of the US Prescribing Information

KVA, Keratopathy and Visual Acuity.


Finding Definition

Mild superficial keratopathy documented worsening from baseline, with or without symptoms

Moderate superficial keratopathy may be accompanied by patchy microcyst-like deposits,

sub-epithelial haze (peripheral), or a new peripheral stromal opacity

Severe superficial keratopathy may be accompanied by diffuse microcyst-like deposits,

sub-epithelial haze (central), or a new central stromal opacity

Corneal epithelial defect such as corneal ulcers.


Reporting Corneal Adverse Events to Hematologist/OncologistsREMS Eye Care Professional Consult Request Form

BCVA, best-corrected visual acuity; OD, oculus dexter (left eye); OS, oculus sinister (right eye), OU, oculus uterque (both eyes); REMS, risk evaluation and mitigation strategy.

• The information that is requested in this form is vital for the prescriber of BLENREP to make treatment and dose modification decisions

• Please complete this form and provide to the prescriber. This form may be faxed, carried by the patient, or adapted into health care technology

Section 1: For Baseline Examination Only

• What are the current best-corrected Snellen Visual Acuity results? OD ____/____ OS ____/_____

Section 2: For Follow-up Examinations

• What are the current best-corrected Snellen Visual Acuity results? OD ____/____ OS ____/_____

• Were there findings upon corneal examination and/or visual acuity assessment? Y / N

o If Y, please check affected eyes OD OS OU

Corneal Examination Findings

Check one

BCVA Changes From Baseline (per Snellen Visual Acuity)

Check one

No change from baseline

Mild superficial keratopathy

Moderate superficial keratopathy

Severe superficial keratopathy

Corneal epithelial defect

Other _______

No change from baseline

Decline from baseline of 1 line

Decline from baseline of 2 or 3 lines (and not worse than 20/200)

Decline from baseline of more than 3 lines (and not worse than 20/200)


Additional corneal examination finding:

There will be two boxes to

complete: one for the right

eye (OD) and one for the

left eye (OS)


Reporting Corneal Adverse Events to Hematologist/OncologistsREMS Eye Care Professional Consult Request Form - Continued

aAdapted and modified from the Prescribing Information; bmild superficial keratopathy (documented worsening from baseline), with or without symptoms; cchanges in visual acuity due to treatment-related corneal findings; d moderate superficial keratopathy with or without patchy microcyst-like deposits, sub-epithelial haze (peripheral), or a new peripheral stromal opacity; esevere superficial keratopathy with or without diffuse microcyst-like deposits, sub-epithelial haze (central), or a new central stromal opacity; fcorneal epithelial defect such as corneal ulcers.BCVA, best-corrected visual acuity; KVA, Keratopathy and Visual Acuity; REMS, risk evaluation and mitigation strategy.

Section 3: What is the current grading from the examination finding(s) and BCVA? (Report the grade for the worst eye by checking the box)

Report the grade for the worst eye by checking the box Grades Corneal Adverse Reaction

Normal Corneal examination finding(s):

Cornea clear/ / No change from baseline

Change in BCVA:

No decline from baseline of 1 line on Snellen Visual Acuity

Grade 1 Corneal examination finding(s):

Mild superficial keratopathyb

Change in BCVAc:

Decline from baseline of 1 line on Snellen Visual Acuity


Moderate superficial keratopathyd

Change in BCVAc:

Decline from baseline of 2 or 3 lines on Snellen Visual Acuity and not worse than

20/200


Severe superficial keratopathye

Change in BCVAc:

Decline from baseline by more than 3 lines on Snellen Visual Acuity and not worse

than 20/200


Corneal epithelial defectf

Change in BCVAc:


Table 1. Corneal Adverse Reactions per the KVA Scalea


Consult the Prescribing Information for BLENREP for other adverse events

The steps below summarize the process for communicating ophthalmic exam results to hematologist/oncologists:

• Assess the patient for corneal examination finding(s) and decline of BCVA

• Determine the most severely affected eye as both eyes may not be affected to the same degree

• Report the grade for the worst eye for examination finding(s) and BCVA to the treating physician by using Table 1 Corneal Adverse Reactions per the KVA Scale

• Communicate findings by completing the Eye Care Consult Request Form

Collaboration and Communication With Hematologist/Oncologists Are Key to Optimal Patient Care

KVA, Keratopathy and Visual Acuity.

Eye care

professional

Hematologist/oncologist will:

• Review ophthalmic exam findings before dosing

• Determine the dose of BLENREP based on worst finding in the worst affected eye

Hematologist/

oncologist


https://d201nm4szfwn7c.cloudfront.net/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/9e0db1d6-8ba2-41bf-82c0-340bd90eca52/9e0db1d6-8ba2-41bf-82c0-340bd90eca52_viewable_rendition__v.pdf


use preservative-free lubricant eye drops at least 4 times a day starting

with the first infusion and continuing until the end of treatment

avoid the use of contact lenses unless directed by an eye care professional

use caution when driving or operating machinery as changes in visual acuity

may be associated with difficulty driving or reading

Patients Receiving BLENREP Should Be Advised To…



Supportive Care and Resources for Patients During Treatment

ECP, eye care professional; HCP, health care provider; REMS, risk evaluation and mitigation strategy.

Patients

Patient

Appointment

Tracker

Eye Drop

Administration

Video

ECP Appointment

Scheduling

Support

Patient

Guide

Medication

Guide

ECP

Locator Tool

Allows patients to have

HCP contacts and a list

of past and upcoming

appointments in

one location

Eye Drop Administration

Guide

Patients can opt in to receive

eye exam appointment

scheduling support for first

two appointments via the

Together With GSK

Oncology Program

(1-844-447-5662)

Medication Guide, also

available here

The Patient Guide includes:• Overview of what to expect

while receiving BLENREP

• Information on risk of eye

problems

• Explanation of REMS

program and how to enrol

with HCP’s help

• A Patient Wallet Card

with Care Team

contact information

Patients can access an Eye Care

Professional Locator Tool here

For help using this tool, patients

may call the Together With

GSK Oncology Program


https://www.webmd.com/find-a-specialist/eye-health


Summary

Eye care professionals play a critical role in the monitoring, mitigation, and management of

corneal adverse events in patients receiving BLENREP

Optimal management of patients’ multiple myeloma is contingent upon prompt eye exams

(visual acuity and slit lamp assessments)

• Patients must have a baseline eye exam before initiating treatment with BLENREP

• Patients must have an eye exam before receiving each dose of BLENREP

• Eye exams must be performed at any sign of worsening eye symptoms

Communication and collaboration between eye care professionals and hematologist/oncologists

are essential for optimal patient outcomes


Resources for eye care professionals are available in the

GSK US Medical Affairs Portal.

Please find links to additional resources below

Eye Care Professional Resources

Eye Care Professional

Training Deck (this slide

deck)


Communications

Handout


Dose Modification

Handout

https://www.gskusmedicalaffairs.com/oncology.html#resources-blenrep-ecr



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