MRD-driven treatment with venetoclax-R2 in mantle cell lymphoma : the Nordic Lymphoma Group MCL7 VALERIA trial
(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.
(Less)
- author
- organization
- publishing date
- 2024-01-23
- 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 < .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}}, }