ESMO Preceptorship Programme

A case of toxicity in Bladder Cancer treated with immuno-therapy

Elena Farè, MD, Medical Oncologist

“Fondazione IRCCS Istituto Nazionale dei Tumori”, Milan (IT)

Bladder Cancer – Side Effects – 24Nov2018

ESMO PRECEPTORSHIP PROGRAMME

DISCLOSURE OF INTEREST

� No conflits of interest to declare

ESMO PRECEPTORSHIP PROGRAMME

Medical Hystory & Initial Diagnosis

� Male, 70 yo, ECOG PS 0

� Former smoker (21 pack-year); hypercholesterolemia; Hypertension.

� March 2015: Gross hematuria � June 2015: Radical cystectomy,

ileal conduit derivation. H.R.: urothelial carcinoma pT2N1 cM0.

� Follow-up complicated by left ureteral stenosis, placement of left

nephrostomy > Chronic renal failure G2 (eGFR 45 mL / min).

Metastatic Recurrence

� January 2016: Recurrence of urothelial carcinoma (pelvic mass).

� From February 2016: Carboplatin/Gemcitabine (6 course); initial PR,

then PD

� Aug2016-Mar2017: weekly Paclitaxel > PD

� Enrolled in immunotherapy clinical trial (phase II, basket). Cohort:

Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg x 4 course (q3w) >

Nivolumab 3 mg/kg (q2w)

� June2017: W1D1 Ipilimumab 3 mg / kg + Nivolumab 1 mg / kg

Toxicities

� D11: Skin Rash (maculo-papular) G3 DR

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diarrhea (stools/day) rash (grade) prednisone (mg) methylprednisolone (mg)

CT =

RP

Ipilimumab3 + Nivolumab1

Nivolumab3

Days

CT =

RP

� D11: Skin Rash G3 DR

� Prednisone 1 mg/kg >

good and complete

resolution

� Therapy DELAY

� W8: 1st CT scan

evaluation > Partial

Response

Toxicities

� D11: Skin Rash G3 DR > treated with Prednisone 1 mg/kg. Therapy

DELAY, but PR at 1st CT scan.

� He received 3 combo IT (Ipi+Nivo). PR

� W12: Diarrhea G1 > G2 … refractory to oral steroid 1 mg/kg >> G3

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diarrhea (stools/day) rash (grade) prednisone (mg) methylprednisolone (mg)

CT =

RP

*Equivocal Lung Nodules

Ipilimumab3 + Nivolumab1

Nivolumab3

H

Days

INFLIXIMAB 5 mg/kg

CT =

RP

CT =

RP*

CT =

RP*

� W12: Diarrhea G3 DR,

refractory to oral steroid 1

mg/kg

� Outpatient evaluation:

dehydration, acute renal

failure, electrolytes

imbalances

� HOSPITALIZATION:

– Infective causes of

diarrhea were ruled

out;

– No signs of colitis

� I.V. Methylprednisolone

2 mg/kg > NO BENEFIT

� INFLIXIMAB

Toxicities

� W1D11: Skin Rash G3 DR > treated with Prednisone 1 mg/kg. Therapy DELAY, but PR at 1st

CT scan.

� He received 3 combo IT (Ipi+Nivo). PR

� W12: Diarrhea G3 DR, refractory to oral steroid 1 mg/kg > HOSPITALIZATION: methylprednisolone i.v. 2 mg/kg, NO benefit > INFLIXIMAB 5 mg/kg > resolution

� STOP combo I/O (3 out of 4 planned) > MM discussion > He continued Nivolumab 3 mg/kg maintenance q2w

� NO FURTHER TOXICITIES

� 8 months after beginning (Feb2018): CT-scan = unequivocal PD (lung, pelvic nodes) > EOT

ESMO PRECEPTORSHIP PROGRAMME

Discussion

� IMMUNOTHERAPY TOXICITY

– Education of the patient

– Accurate and rapid evaluation

� INTEGRATED MANAGEMENT

– Outpatient vs Hospital admission

– Accurate diagnosis

� QUICK INTERVENTION

– Steroid with maximal dosage

– Do not delay Infliximab if necessary

ESMO Preceptorship Programme

Thank for your attention!

Elena Farè, MD (Italy - Milan)