Adding ibrutinib to induction chemotherapy and using ibrutinib as maintenance after autologous stem cell transplant (ASCT) improves failure-free survival (FFS) in patients with mantle cell lymphoma (MCL), according to results from the phase 3 TRIANGLE study.
The study showed that FFS was significantly better for patients who received chemotherapy-ibrutinib induction, ASCT, and 2 years of ibrutinib maintenance than for patients who were treated with chemotherapy induction, ASCT, and observation.
Results also showed that FFS was no better for patients who received chemotherapy induction and ASCT than for patients who received chemotherapy-ibrutinib induction and ibrutinib maintenance for 2 years without ASCT.
These results were presented at the 2022 ASH Annual Meeting by Martin Dreyling, MD, PhD, of University Hospital Munich in Germany.
The TRIANGLE trial (ClinicalTrials.gov Identifier: NCT02858258) enrolled patients with previously untreated, stage II-IV MCL who were suitable for high-dose cytarabine and ASCT. A total of 870 patients were included. Their median age at baseline was 57 years (range, 27-68), 76% were men, and 87% had stage IV disease (87%).
All patients received induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) for 3 cycles, but patients were randomly assigned to 3 treatment arms according to the administration of ibrutinib and the use of ASCT. The 3 treatment arms were:
- R-CHOP or R-DHAP induction followed by ASCT and observation (control arm; n=288)
- R-CHOP plus ibrutinib or R-DHAP induction followed by ASCT and 2 years of ibrutinib maintenance (ASCT-ibrutinib arm; n=292)
- R-CHOP plus ibrutinib or R-DHAP and 2 years of ibrutinib maintenance (ibrutinib-alone arm; n=290).
Some patients also received rituximab maintenance — 58% in the control arm, 57% in the ASCT-ibrutinib arm, and 54% in the ibrutinib-alone arm. Baseline characteristics were well balanced across the arms.
Efficacy and Safety Results
At the end of induction, the overall response rate (ORR) was 94% in the control arm, 98% in the ASCT-ibrutinib arm, and 98% in the ibrutinib-alone arm. The complete response (CR) rates were 36%, 44%, and 45%, respectively.
The ORR was significantly higher in the combined ibrutinib-containing arms than in the control arm (P =.0025). The CR rate was significantly higher in the ibrutinib-containing arms as well (P =.0203).
The 3-year FFS rate was significantly higher in the ASCT-ibrutinib arm than in the control arm — 88% and 72%, respectively (hazard ratio [HR], 0.52; P=.0008). The 3-year FFS rate was 86% in the ibrutinib-alone arm, compared with 72% in the control arm (HR, 1.77; P=.9979).
The investigation comparing the ASCT-ibrutinib arm with the ibrutinib-alone arm is ongoing, Dr Dreyling said.
Overall survival results could not be evaluated for statistical significance. However, the 3-year overall survival rate was 86% in the control arm, 91% in the ASCT-ibrutinib arm, and 92% in the ibrutinib-alone arm.
During induction, rates of grade 3-5 adverse events (AEs) were similar with R-CHOP/R-DHAP alone vs ibrutinib plus R-CHOP/R-DHAP. Rates of grade 3-5 AEs were similar between the ASCT-containing arms as well.
However, during maintenance, there were more grade 3-5 AEs in the ASCT-ibrutinib arm than in the control arm and the ibrutinib-alone arm, including for blood and lymphatic system disorders (50%, 21%, and 28%, respectively), infections and infestations (25%, 13%, and 19%), gastrointestinal disorders (6%, 3%, and 4%), and other AEs.
Disclosures: This research was supported by Janssen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized TRIANGLE trial by the European MCL Network. Presented at ASH 2022. December 10-13, 2022. Abstract 1.