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Table 2 Clinical trials have been conducted targeting various parts of MCL pathophysiology

From: Mantle cell lymphoma and its management: where are we now?

Target Study Setting Phase Regimen ORR CR PFS OS
1 Proteasome inhibitor
Fisher et al. [33] Relapsed I/II V 33% 8% NA NA
Ruan et al. [34] Front line I/II V + RCHOP 91% 64% 23 months NR
Till BG et al. [36] Front line II V + RCHOP 83% 57% 29.5 months NR
Chang et al. [37] Front line II V + Modified R-HyperCVAD (VcR-CVAD) and MR for 5 years 90% 77% 8.14 years NR
2 Bruton’s tyrosine kinase inhibitor
Rule et al. [40] Relapsed/refractory PA Ibrutinib monotherapy 69.7% 26.5% 13 months 26.7 months
Wang et al. [41] Relapsed/refractory II Ibrutinib + R 88% 44% 75% (12 months) 85.5% (12 months)
Maddocks et al. [42] Relapsed or new MCL I/Ib Ibrutinib + BR 94% 76% NA NA
Wang et al. [44] Relapsed II Acalabrutinib 81% 40% 67% (12 months) 87% (12 months)
Walter et al. [45] Relapsed I ONO/GS-4059 92% 46% NA NA
Tam et al. [46] Relapsed II Ibrutinib+venetoclax 71% 62% NA NA
3 Epigenetic agents
Pu et al. [48] New or relapsed/refractory MCL I/II Cladribine + R + V 85% 77% NR NR
Spurgeon et al. [47] New or relapsed MCL, CLL, NHL II Vorinostat + Cladribine + R 97% (untreated MCL) 80% (untreated MCL) 70.7% (24 months) 86% (24 months)
Puvvada et al. [49] New or relapsed MCL and indolent NHL II Cladribine + R + V 100% 50% 82% (24 months) 91% (24 months)
4 Immunomodulatory agent
Goy et al. [50] Relapsed II Len monotherapy 28% 7.5% 4 mon 19 mon
Habermann et al. [51] Relapsed II Len monotherapy 53% 20% 5.6 mon NA
Witzig et al. [52] Relapsed II Len monotherapy 42% 21% 5.7 mon NA
Wang et al. [54] Relapsed/refractory I/II Len + R 57% 36% 11.1 mon 24.3 months
Ruan et al. [55, 56] First line II Len + R 92% 64% Not reached 97% (2 years OS)
Morrison et al. [53] Relapsed/refractory II Len + V 39.6% 15.1% 7 months 26 months
Albertsson-Lindblad et al. [57] First line I/II Len + BR 91% 78% 42 months 53 months
5 mTOR kinase inhibitors
Hess et al. [58] Relapsed/refractory III Temsirolimus vs. investigator’s choice 6–22% 0–2% 4.8–3.4 months 12.8–10 months
Witzig et al. [59] Relapsed II Temsirolimus monotherapy 30% 3% 6.5 months 12 months
Ansell et al. [60] Relapsed II Temsirolimus monotherapy 41% 3.7% 6 months NA
Wang et al. [62] Refractory to V II Everolimus monotherapy 8.6% 0% 4.4 months 16.9 months
Hess et al. [61] Relapsed I Temsirolimus + BR 92% 45% NA NA
6 CART and BiTE
Abramson et al. [66] Relapse/refractory Pivotal trial Lisocabtagene maraleucel (JCAR017) 72% (NHL) 52% (NHL) NA NA
ZUMA-2 [68] Relapsed/refractory II Axicabtagene ciloleucel NA NA NA NA
Goebeler et al. [69] Relapsed/refractory I Blinatumomab 71% NA NA NA
Dufner et al. [70] Relapsed/refractory I Blinatumomab NA NA 204 days 1560 days
Budde et al. [71] Relapsed/refractory I Mosunetuzumab 41% NA NA NA
  1. V Bortezomib; R rituximab; RCHOP rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; R-HyperCVAD rituximab, hyperfractionated cytarabine, vincristine, doxorubicin and dexamethasone; MR maintenance rituximab; BR Bendamustine and rituximab; Len Lenalidomide; CART Chimeric antigen receptor-engineered T-cells; BiTE Bi-specific T-cells Engager; NA not available; NR not reached; PA pooled analysis