Jeremy S. Abramson, MD

Jeremy S. Abramson, MD, Director of Lymphoma, Mass General Cancer Center, Boston, commented on the clinical implications of the TRIANGLE study.

“The TRIANGLE trial is a large, three-arm randomized trial addressing two critically important questions in the management of younger patients with mantle cell lymphoma. Standard therapy in this population consists of intensive cytarabine-based induction therapy, followed by consolidative autologous stem cell transplantation [ASCT] followed by maintenance rituximab. The first question is whether adding a BTK [Bruton’s tyrosine kinase] inhibitor to front-line therapy will improve outcomes. The second question is whether we still need to perform autologous transplants routinely in the modern era, where we have dramatically improved induction therapy, maintenance therapy, and novel targeted therapies,” Dr. Abramson commented.

Current Take on These Questions

Dr. Abramson continued: “Regarding the first question, the addition of ibrutinib to R-CHOP/R-DHAP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone/rituximab, dexamethasone, cytarabine, cisplatin] followed by maintenance ibrutinib significantly improved progression-free survival and even included a nonsignificant trend toward improvement in overall survival. The improved progression-free survival in this younger population was achieved without significant additional toxicity from ibrutinib. These data support the addition of ibrutinib to R-CHOP/R-DHAP as induction therapy and to rituximab as maintenance therapy in younger patients with mantle cell lymphoma,” he stated.

“Regarding the second question about the role of autologous transplant, the data thus far show completely overlapping progression-free survival curves in patients who received ibrutinib maintenance with or without autologous transplant. This comparison remains immature so is not yet definitive, but it certainly appears likely that modern induction therapy followed by ibrutinib, and rituximab maintenance will obviate the need for ASCT in the initial treatment paradigm, which would be a tremendous advance for patients,” Dr. Abramson said.

“When considering these data, it is important to note that we no longer favor ibrutinib for treatment of relapsed or refractory mantle cell lymphoma, instead favoring the next-generation inhibitors zanubrutinib and acalabrutinib due to a more favorable toxicity profile. The safety results in TRIANGLE do appear manageable, and so in the absence of additional data with the alternate agents, ibrutinib would be the BTK inhibitor of choice with initial therapy in younger patients with mantle cell lymphoma,” Dr. Abramson said.

TRIANGLE vs SHINE

“Hopefully, additional data allow us to substitute newer safer agents in the future. My interpretation of the TRIANGLE data is notably in contrast to the SHINE trial, which evaluated ibrutinib in combination with bendamustine/rituximab in older patients with mantle cell lymphoma. In the SHINE trial, ibrutinib improved progression-free survival, but at the cost of significantly more toxicity and with no hint of improved overall survival. So, I do not favor adding ibrutinib to bendamustine/rituximab in older patients who appear to be more susceptible to ibrutinib toxicity,” Dr. Abramson stated. 

DISCLOSURE: The study was supported by Janssen. Dr. Abramson has served as a consultant to AbbVie, BMS, Genentech, Genmab, Janssen, Kite Pharma, Lilly, MorphoSys, and Regeneron.