Dr Dreyling on Safety Data With ASCT Plus Ibrutinib and Rituximab in Lower-Risk, Younger MCL

“[In TRIANGLE, during] follow-up, [54% of patients who received rituximab, ibrutinib, and ASCT] had myelosuppression [or other blood and lymphatic system disorders]. [The addition of ASCT] also translated to an increased rate of infections during the 2-year follow-up period. Therefore, ASCT should be only applied when it must be and only in high-risk patients.”

Martin Dreyling, MD, full professor, Department of Medicine, University Hospital LMU Munich, discusses updated safety results from the randomized phase 3 TRIANGLE trial (NCT02858258), which evaluated the addition of autologous stem cell transplantation (ASCT) to ibrutinib (Imbruvica) plus chemotherapy and rituximab (Rituxan) maintenance in the first-line setting for younger patients with mantle cell lymphoma (MCL).

Updated data presented at the 2024 ASH Annual Meeting showed that at a median follow-up of 55 months, treatment with chemotherapy and rituximab plus ASCT (arm A; n = 288) did not result in superior failure-free survival (FFS) compared with chemotherapy, rituximab, and ibrutinib without ASCT (arm I; n = 290). However, the addition of ASCT to chemotherapy, rituximab, and ibrutinib (arm A+I; n = 292) did not significantly improve FFS over arm I (4-year FFS rate, 82% vs 81%; 1-sided P = .21; HR, 0.83). Overall survival findings also suggested that ASCT does not provide additional survival benefit when combined with chemotherapy, rituximab, and ibrutinib.

Safety data indicate that patients, particularly those with high-risk MCL, benefited from rituximab and ibrutinib maintenance; however, out of these 3 [treatments], ASCT is associated with the highest toxicity burden, Dreyling continues. Myelosuppression and other blood and lymphatic system disorders occurred in 54% of patients in arm A+I, approximately twice the rate observed in the other trial arms, he reports. Additionally, the rate of infections during the 2-year follow-up period was higher in arm A+I (34%) compared with arm I (26%), Dreyling notes.

Given the increased toxicity associated with ASCT, the findings suggest that this approach should be reserved for high-risk patients who would derive the most benefit, Dreyling says. For many patients with MCL, the combination of chemotherapy, rituximab, and ibrutinib without ASCT may represent a less toxic and equally effective treatment strategy, he concludes.