Should all patients with FL receive maintenance therapy? · 2020. 12. 23. · Advisory Board:...

Should all patients with FL receive maintenance therapy?

Guilherme Perini, MD

guilherme.perini@bp.org.br

Disclosures

Speakers Bureau: Janssen, Roche, Takeda, Abbvie, BMS

Educational Support: Janssen, Takeda, Roche, Abbvie

Advisory Board: Janssen, Abbvie, Astra Zeneca

Research: Janssen, Millenium, Merck, Alnylam

Slides will be presented in English for better comprehension of invitedspeakers

Questions to be adressed

• What should be our goal in FL?

• What does longer follow up of studies tells us about Rituximabmaintenance?

• Does induction chemo influences maintenance results?

• Are new MoAbs suitable for Maintenance?

• How safe is maintenance?

What should be our goal

in FL?

What should be our goal in FL?

56 y/o patient

Stage IIIB FL

6x R-CHOP, denied RM

EOT PET: residual 3cm lymph node

1y: Abd CT shows a 5cm lymph node

4 years later, B-symptoms

4x R: PR

Denied again MR

6y: Multiple LFN, assymptomatic

76 y/o patient

Stage IVA FL

6x R-CHOP + RM

EOT PET: PR

6m – PET : CR

RM 14 month: Herpes Zoster

Postherpetic neuralgia requiring opioids

2y: CR

Opioid abuse?

2.5y: Aspiration PNM due to opiod abuse

- 13days in ICU

- 24 days inpatient

3y: CR, PS 2

What should be our goal in FL?

56 y/o patient

Stage IIIB FL

6x R-CHOP, denied RM

EOT PET: residual 3cm lymph node

1y: Abd CT shows a 5cm lymph node

4 years later, B-symptoms

4x R: PR

Denied again MR

6y: Multiple LFN, assymptomatic

76 y/o patient

Stage IVA FL

6x R-CHOP + RM

EOT PET: PR

6m – PET : CR

RM 14 month: Herpes Zoster

Postherpetic neuralgia requiring opioids

2y: CR

Opioid abuse?

2.5y: Aspiration PNM due to opiod abuse

- 13days in ICU

- 24 days inpatient

3y: CR

PFS Event: 1yTTNT: 4yOS Event: None

PFS Event: NoneTTNT: NoneOS Event: None

What should be our goal in FL?

First, do no harm.

PFS is a goal for some patients

Safety is a goal for others

OS is a goal for ALL patients

Talk to your patients. Reevaluate your decisions. Avoid regret.

What does longer follow up of studies tellsus about Rituximab maintenance?

Maintenance in R/R FL: EORTC 20981

Van Oers, JCO 2010

EORCT 20981: 6y F/U

Van Oers, JCO 2010

Major Causes of death in PRIMA – 10y update

Cause of death Observation R-Maintenance

Lymphoma 38 39

Malignancies 24 6

Myeloid 7 2

Infection 6 11

Cardiovascular 4 8

TTNT: 6.1 years Obs x NR in the R-maintenance arm (P<.0001; HR=0.66; 95%CI 0.55-0.78)

10-year Free from treatment: 53% x 41%

What about retreatment? RESORT Study

Median R doses:

RR: 4MR: 18

Khal B, JCO 2014

Resort Study

Khal B, JCO 2014

RESORT Study

Khal B, JCO 2014

Beware of Comparisons!

PRIMA RESORT

Tumor Burden High Low

Induction R-Chemo R-single agent

Depth of response after induction +++ +

Follow up 10 4.5

Does induction chemo influencesMaintenance?

STIL Study

STIL 10 y Follow up

Still 10y OS

BRIGHT Study

R-Maintenanceby investigators’discretion

BRIGHT Study – DOR

BRIGHT Study – OS

MAINTAIN Study – 2 x 4y RM after BR

Rummel et al, Blood 2017

MAINTAIN – PFS RM 2 x 4y

Rummel et al, Blood 2017

MAINTAIN – OS from Randomization

Rummel et al, Blood 2017

STIL x Maintain: PFS

STIL x MAINTAIN: No OS Benefit

Conclusions

• Chemo backbone impacts the benefit of RM• All groups benefit in PFS

• No benefit after BR in OS

• Trend for OS benefit in R-CHOP/R-CVP

• BR patients achieving CR• No Benefit in MR

• Retrospective registry study

• Toxicity is also impacted

Are new MoAbs suitable for Maintenance?

GALLIUM Study

Only the UK Likes R-CVP

Response after induction (FL)

PFS: R x G

PFS for FL: R x G

TTNT (FL): R x G

OS (FL): G x R

How safe is maintenance?

How Safe is Maintenance?

Pretty Safe!

With Rituximab

• 7%+ events on PRIMA

• More Grade 3 Events (infections)

• No safety signal after 10 years of PRIMA

Gallium Safety analysis

G-Bendamustine particularlyproblematic

IMMUNOCHEMOTHERAPY WITH OBINUTUZUMAB OR RITUXIMAB IN a SUBSET OF PATIENTS IN THE RANDOMISED GALLIUM TRIAL WITH PREVIOUSLY UNTREATED MARGINAL ZONE LYMPHOMA (MZL)

Conclusions

• Not all patients should receive Maintenance after Induction• Patient informed and centered-decision• >80% decide for R-Maintenance and I am OK with it

• Dont push your patient too hard• Its OK to STOP Maintenance if toxicity• You are NOT avoiding LYMPHOMA DEATHS with Maintenance (PRIMA)

• I dont use RM after BR• I avoid GB in first line therapy, especially in older patients• I will not use GM after GB in first line therapy of FL• I have used GM after GB in second-line therapy in some patients

Obrigado!

guiperini@gmail.com

(11) 99292 – 6463

@guiperini