High risk Mantle cell lymphoma

 Mantle cell lymphoma

ASH education book 2024

1. Identify biologic MIPI( MIPI+Ki67), aggressive biology( blastoid, pleomorphic), high risk genetics ( 17p, TP 53 mutations, complex cytogenetics). 

2. p53 accumulates in the cell in TP53 mutations > 30-50%. Stain by IHC. CIT ( Chemo/ASCT) can overcome neg impact of p53 mutations. Unclear significance of TP53 in the leukemic, non nodal variant.

3. Blastoid has a 5 yr OS of 35%. LYMA study high MIPI 5 yr OS 47%.

4. Approach to pt with p53 mutations: avoid benda in 1st line or second line, they do not do well even with intensive CIT or BTK and should be planning CAR-T. 

5. Allogeneic stem cell transplantation, as consolidation during the first CR or at first relapse, is a consideration for select eligible patients, particularly where CAR T-cell therapy is not available.

6. Two main strategies have been pursued to improve outcomes in MCL, including in high-risk patients: (1) incorporating novel agents with CIT and (2) substituting CIT with a combination of novel agents.

7. There were 2 trials that evaluated BTKi ( ibrutinib or acala) with BR in elderly. No OS benefit although PFS improved. High toxicity. p53 group did not benefit in the SHINE trial (ibrutinib).

8. TRIANGLE study: younger, ASCT eligible pt. 3 yr FFS in both ibrutinib groups 88% including high p53 > 50%.

9. Chemo free regimens upfront can involve a BTKi+ Ven+ CD 20 antibody. Acala+ Lenalidomide+ Obin or Ven+ R2 have shown excellent PFS and 2 yr OS in phase 2 trials.  boVEN Zanubrutinib+ Obin+ Ven 

10. An Ara-C-containing intensified induction therapy followed by ASCT remains a highly effective treatment strategy in younger MCL patients, inducing long-lasting remissions. However, no randomized trial has shown an OS benefit with ASCT when modern rituximab-based regimens are used.

 Summary:

Frontline- TP53 aberrant( high p53, 17p, TP53 mutations)---> options clinical trials or BTKi-CIT followed by 3 yr rituxan maintenance or BTKi+BCL2i+CD20 Ab. No benefit to intensive CIT and ASCT in TP53mutated.

Other high risk- trial, or CIT+ BTK+rituxan maintenance

Non high risk- Intensive CIT followed by ASCT in fit younger pt < 66 yr or TRIANGLE regimen without ASCT.