MRD-driven treatment with venetoclax-R2 in mantle cell lymphoma: the Nordic Lymphoma Group MCL7 VALERIA trial

Mats Jerkeman*, Arne Kolstad, Martin Hutchings, Annika Pasanen, Leo Meriranta, Carsten Utoft Niemann, Rasmus Rask Kragh Jørgensen, Tarec Christoffer El Galaly, Jon Riise, Sirpa Leppä, Jacob Haaber Christensen, Kristina Sonnevi, Lone Bredo Pedersen, Karin Fahl Wader, Ingrid Glimelius

*Corresponding author af dette arbejde


Despite improvements in treatment of mantle cell lymphoma (MCL), most patients eventually relapse. In this multicenter phase 1b/2 trial, we evaluated safety and efficacy of minimal residual disease (MRD)-driven venetoclax, lenalidomide, and rituximab (venetoclax-R2) in relapsed/refractory (R/R) MCL and explored the feasibility of stopping treatment in molecular remission. The primary end point was overall response rate (ORR) at 6 months. After dose escalation, the recommended phase 2 dose was lenalidomide 20 mg daily, days 1 to 21; venetoclax 600 mg daily after ramp-up; and rituximab 375 mg/m2 weekly for 4 weeks, then every 8 weeks. MRD monitoring by RQ-PCR was performed every 3 months. When MRD-negativity in the blood was reached, treatment was continued for another 3 months; if MRD-negativity was then confirmed, treatment was stopped. In total, 59 patients were enrolled, with a median age of 73 years. At 6 months, the ORR was 63% (29 complete remission [CR], 8 partial remission [PR]), and 40% (4 CR, 2 PR) for patients previously failing a Bruton tyrosine kinase (BTK) inhibitor. Median progression-free survival (PFS) was 21 months, with median overall survival of 31 months. TP53 mutation was associated with inferior PFS (P < .01). Overall, 28 patients (48%) discontinued treatment in molecular remission, and 25 remain MRD negative after a median of 17.4 months. Hematological toxicity was frequent, with 52 of 59 (88%) patients with G3-4 neutropenia and 21 of 59 (36%) patients with G3-4 thrombocytopenia. To conclude, MRD-driven venetoclax-R2 is feasible and tolerable and shows efficacy in R/R MCL, also after BTK inhibitor failure. This trial was registered at as #NCT03505944.

TidsskriftBlood advances
Udgave nummer2
Sider (fra-til)407-415
Antal sider9
StatusUdgivet - jan. 2024


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