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

Jerkeman, Mats LU ; Kolstad, Arne ; Hutchings, Martin ; Pasanen, Annika ; Meriranta, Leo ; Niemann, Carsten Utoft ; Jørgensen, Rasmus Rask Kragh ; El-Galaly, Tarec Christoffer ; Riise, Jon and Leppä, Sirpa , et al. (2024) In Blood Advances 8(2). p.407-415
Abstract

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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
8
issue
2
pages
9 pages
publisher
American Society of Hematology
external identifiers
  • pmid:38113470
  • scopus:85183001139
ISSN
2473-9529
DOI
10.1182/bloodadvances.2023011920
language
English
LU publication?
yes
id
f061f26a-34e6-433a-a3c7-1a5b08977aab
date added to LUP
2024-02-22 10:12:22
date last changed
2024-04-21 19:54:46
@article{f061f26a-34e6-433a-a3c7-1a5b08977aab,
  abstract     = {{<p>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 &lt; .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.</p>}},
  author       = {{Jerkeman, Mats and Kolstad, Arne and Hutchings, Martin and Pasanen, Annika and Meriranta, Leo and Niemann, Carsten Utoft and Jørgensen, Rasmus Rask Kragh and El-Galaly, Tarec Christoffer and Riise, Jon and Leppä, Sirpa and Christensen, Jacob Haaber and Sonnevi, Kristina and Pedersen, Lone Bredo and Wader, Karin Fahl and Glimelius, Ingrid}},
  issn         = {{2473-9529}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{407--415}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{MRD-driven treatment with venetoclax-R2 in mantle cell lymphoma : the Nordic Lymphoma Group MCL7 VALERIA trial}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2023011920}},
  doi          = {{10.1182/bloodadvances.2023011920}},
  volume       = {{8}},
  year         = {{2024}},
}