In this video update, Dr Matthew J. Matasar shares highlights from the American Society of Hematology 64th Annual Meeting. Watch as he discusses trial data presented at the conference and gives his view on the key takeaways for clinical practice.

 

Clinical takeaways:

  • The TRIANGLE trial supports the use of ibritunib in the first-line treatment of younger mantle cell lymphoma patients
  • The ALPINE study demonstrates progression-free survival and overall response rate superiority of zanubrutinib to ibrutinib in patients with R/R CLL/SLL
  • The REMoDL-B trial supports that gene expression profiling can identify subtypes of DLBCL which may benefit from the addition of bortezomib to R-CHOP in initial therapy, specifically, ABC and MHG types

Hi, I'm Dr. Matt Matasar. I'm the chief of blood disorders at the Rutgers Cancer Institute in New Jersey. And I'm here at ASH 2022 to share some important updates with you.

 

I'm going to talk to you about three important advances that we saw reported here at ASH, the first of which was indeed the first abstract presented, the number one piece in the plenary session. And this is the TRIANGLE study reported by the European Mantle Cell Network. This is an important study, a three-armed prospective randomised trial, comparing different strategies in the treatment of young fit patients with newly diagnosed Mantle cell lymphoma. Arm one was what they would consider standard of care, which is alternating cycles of R-CHOP and R-DHAP, and a consolidated auto transplant in first remission. The second arm is that same approach, but incorporating ibrutinib, adding it to the R-CHOP cycles and adding in two years of post-transplant maintenance ibrutinib. In the third arm is the investigational arm in which again R-CHOP plus ibrutinib alternates with R-DHAP. No auto transplant is given. Patients transition directly to two years of ibrutinib maintenance.

While we saw differences in improvement in the incorporation of ibrutinib on top of chemotherapy when patients were receiving an auto transplant, this is not necessarily surprising. More importantly to us, however, when you compare the investigational arm, R-CHOP plus ibrutinib, alternating with R-DHAP, no transplant ibrutinib maintenance, it was actually numerically superior in an important endpoint such as progression-free survival compared to the standard of care arm of R-CHOP, R-DHAP and an auto transplant, suggesting that it may be the case when we see the full data, that we may be able to move away from a standard of care auto transplant in first remission. Replacing that with a more tolerable and less toxic two-year ibrutinib maintenance strategy.

 


The second abstract I'll now bring to your attention is the ALPINE study. This is a head-to-head clinical trial of zanubrutinib in second generation BTK inhibitor to ibrutinib in patients with CLL that are BTK naive. We've long believed that zanubrutinib is a slightly more tolerable treatment than ibrutinib with lower rates of key toxicities, such as atrial fibrillation and bleeding. But it is clear from the ALPINE data, with important progress in clinically meaningful endpoints like progression-free survival, that zanubrutinib is indeed a better treatment for such patients, than ibrutinib in the head-to-head fashion. Both arms did well. We know that both are effective drugs, but this does indeed establish zanubrutinib of as a standard of care treatment in patients with CLL.


Lastly, I think the sleeper study of the Congress was the updated results from the REMoDL-B study. This was a prior conducted randomised trial in patients with newly diagnosed diffuse
large B-cell lymphoma to receive either standard of care R-CHOP or R-CHOP plus bortezomib. The hypothesis was that bortezomib as an NF-κB sort of pathway inhibitor should be differentially active in activated B-cell subtype diffuse large B-cell lymphoma.


Prior data cuts showed the study to be negative. However, with these updated results at this Congress, combined with a reclassification of patients according to molecular classification as opposed to the more old-fashioned and less accurate immunochemical signature, we see that in patients with true activated B-cell by sequencing or a second subtype called molecular high grade - again by sequencing, these patients derived significant benefit from the inclusion of bortezomib, with improvements in progression-free and overall survival compared to R-CHOP alone. We'll definitely want to see these full data, but it establishes R-CHOP plus bortezomib as a potential new standard of care for such patients.

 

So, what's my takeaway from ASH this year? From these three abstracts, I think that we're seeing tremendous progress in the treatment of patients with B-cell lymphomas. We're seeing treatments that are more effective, zanubrutinib beating ibrutinib head-to-head. Improvements in first-line therapy for activated B-cell molecular high-grade DLBCL with the inclusion of bortezomib. As well as finding ways to give effective and less toxic treatments, sparing patients auto transplant potentially with the inclusion of ibrutinib in first-line therapy mantle cell lymphoma.

 

Again, I'm Dr. Matt Matasar from the Rutgers Cancer in New Jersey, and thanks for your attention.

Dr Matthew Matasar is a board-certified medical oncologist/hematologist, who received his undergraduate and medical degrees from Harvard University. His internal medicine training was completed at Columbia Presbyterian, where he earned a Master’s in biostatistics, while serving as Chief Resident. His fellowship training was in medical oncology at Memorial Sloan Kettering Cancer Center, where he subsequently joined faculty on the Lymphoma and Adult BMT services. Dr Matasar is also the Director of the Lymphoma Survivorship Clinic, where he focuses on the management of long-term survivors of Hodgkin and non-Hodgkin lymphoma. As the Section Head for Aggressive B-cell Lymphomas, his research is focused on improving outcomes in relapsed but curable patients using novel therapies. He is the Medical Director at MSK Bergen, directing a team of expert oncologists in the delivery of cutting-edge care across cancer service lines to patients at the free-standing outpatient center in Montvale, New Jersey.

Dr Matthew J. Matasar has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Bayer, Bayer Pharmacyclics, Genentech, GlaxoSmithKline, Immunovaccine Tech, Janssen, Juno Theraputics, Merck, Roche Rocket Medical, Seattle Genetics, Teva and Takeda.

 

 

 

Lymphoma Update from ASH 2021

Dr. Matthew J. Matasar summarises the highlights in lymphoma from ASH 2021, including POLARIX, CAR-T in LBCL and mosunetuzumab in FL

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Update from ASH 2019

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