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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
