Follicular Lymphoma (1:23 -10:35)
Update to ESMO/EHA therapeutic algorithm
For high tumour burden consider antibody maintenance (or radioimmunotherapy)
Dreyling, Ann Oncol 2021
Frontline
FOLL12 Study
Response adapted post-induction strategy in patients with advanced-stage follicular lymphoma (Luminari, ASH 2021)
- High Tumour Burden, no previous treatment
- Comparing Induction therapy 6x R-CHOP+2R vs 6x R-Benda+2R
Key takeaways:
- PFS similar
- Differences in toxicity
- Less alopecia (a patient preference)
- Higher Infection and skin SAE with BR vs R-CHOP
- Post induction – higher neutropenia with BR
First relapse/progression
ESMO/EHA therapeutic algorithm, (Dreyling, Ann Oncol 2021)
MAGNIFY Study (Lansigan F, et al. ASH 2021)
Phase 3b Study of Lenalidomide + Rituximab (R2) Followed by Maintenance
- Building on current ESMO/EHA algorithm this study compares RL induction followed by maintenance or RL or R
Key takeaways:
- R2 is active with a tolerable safety profile
- Median PFS (95% CI)
3RD LINE
Immunotherapy has a place for rrFL high risk patients
BiTEs
Phase I/II GO29781 study (Morschhauser, ASH 2021)
- mosunetuzumab+ lenolidomide
Key Takeaways:
- induces high and durable complete response rates in people with follicular lymphoma who have received two or more prior therapies
- 90% ORR.
CAR T
ZUMA-5: Long-Term Follow-up Analysis of Axi-cel, (Neelapu et al. ASH 2021)
- Very high-risk R/R FL patients
- median > 3 prior treatments
- POD 24 in the majority from first anti-CD20 mAb- containing therapy
Key Takeaways:
- ORR 94%
- CR 79%
- 1 time treatment long term PFS is holding up after 36 months
- Median OS was not yet fully reached in the efficacy-eligible patients
Current GLA (German Lymphoma Alliance) studies in 2022
R2+/- Tazemetostat
R2+/- Tafasitamab
R2 vs Mosunetuzumab
Mantle Cell (10.35 –24:35)
Standard of Care [update from EU]
1st line for Younger Patients (<65)
Current EU approach: Dose intensified immune-chemotherapy (R-CHOP, high dose Ara-C) -> aSCT -> R maintenance
Update: Substitute 3 cycles of R-CHOP with 3 cycles of R-DHAP, (an update by Hermine, et al. ASH 2021)
Key Takeaway:
- Median TTF : R-DHAP 8.4 years R-CHOP 3.9 years
- 10-year TTF (95% CI): R-DHAP 46% (39% – 54%) R-CHOP 25% (19% – 32%)
- 10 year OS also improved with R-DHAP vs R-CHOP
1st line for Elderly Patients (>65)
Role of Rituxan (R) maintenance after first-line BR or R-CHOP, (Salles, EHA 2021)
Key Takeaway:
- Maintenance improves PFS after R-CHOP and BR and translates into significant benefit in OS
1st relapse
Which patients will benefit from targeted approaches?
Ibrutinib in relapsed MCL (POD 24), Visco, Leukemia 2021
- Ibrut vs R-B or R-BAC
- Young fit patients
Key Takeaways:
- Ibrut beneficial for patients who relapse within 2 years with significant O/S benefit
- Late POD no difference
- Based on results Ibrut is strongly pushing into first-line
MCL-R2 Elderly, (Ribrag et al. ASH 2021)
Rituximab-Lenalidomide(R2) after first Line Immunochemotherapy
Key Takeaways:
- R2 Maintenance is superior to R maintenance for PFS but not OS.
- Safety data showed more toxicity in the R2M arm.
Emerging Treatments /Other ongoing trials
Front-line for Elderly Patients
Phase III SHINE and ENRICH Trials
- Comparing Ibrut to progression with BR-> R maintenance vs BR -> R maintenance
- ·s Chemo-free as good as CIT?
Phase II MCL ELDERLY III
- Comparing Ibrut vs Ven with BR-> R maintenance
- Best chemo free combo? Is cessation possible?
TRIANGLE
- 3xR-CHOP+ I -> I+R maintenance vs 3xR-CHOP+ I -> ASCT+R maintenance
Failure after Ibrutinib
CAR -T Brexu-Cel – Real World Experience from the US Lymphoma CAR T Consortium (Wang et al ASH 2021)
Key Takeaways
- High-risk patient population with 82% prior BTKi and 35% Ven
- Day 30 ORR of 88% (66% CR and 22% PR).
- Best ORR comparable to ZUMA-2 trial of 93%
BiTEs – Glofitamab (Philips, ASH 2021)
Key Takeaways:
- Glofitamab in combo with obintuzumab
- Majority pretreated with BTKi and almost 90% refractory
- ORR: 81% and CMR: 67
Irreversible non-covalent BTKi – Phase I/II BRUIN Study (Wang, ASH 2021)
Key Takeaways:
- Pirtobrutinib, LOXO-305
- Duration of Response in Mantle Cell Lymphoma
- Median follow-up of 8.2 months (range, 1.0 – 27.9 months) for responding patients
- 60% (36 of 60) of responses are ongoing
