Assessing Novel Non-Chemotherapy Agents as Initial Therapeutic Options for Patients With Mantle Cell Lymphoma

During the 2024 Great Debates and Updates (GDU) in Hematological Malignancies Meeting, Jia Ruan, MD, PhD, Weill Cornell Medicine, New York, discusses the emergence of novel agents in the treatment of mantle cell lymphoma (MCL), focusing on the use of Bruton’s tyrosine kinase (BTK) inhibitors.

Transcript:

Hi, good morning. I'm Dr. Jia Ruan. I'm a physician taking care of patients with lymphoma at Weill Cornell, New York Presbyterian Hospital.

It's my pleasure to be here today. We have a conference, [the] Great Debate[s] & Update[s] in Hematologic Malignancies meeting in New York]. The topic that I [presented] for today's meeting is on the frontline treatment of patients with mantle cell lymphoma. In particular, I discuss[ed] non-chemotherapy novel treatment combination[s].

I think it's a very exciting area for research for mantle cell lymphoma. As you know, traditionally, patients were treated with chemoimmunotherapy. Because of the intensity of the treatment, oftentimes we have to stratify patients based on their age, their physical fitness, and obviously, disease risk factors.

Younger patients [are] generally treated with very intense chemotherapy, including high-dose cytarabine, sometimes consolidation with autologous stem cell transplant, and then rituximab. For more elderly patients, we [have] a different chemoimmunotherapy backbone, such as bendamustine-rituximab, and oftentimes, we apply rituximab as maintenance.

In the last decade, I would say the emergence of novel treatment[s] has really changed the care for patients with mantle cell lymphoma. Many of those novel agents are pills that can be taken at home, very conveniently, [and] safely, making the treatment with highly effective agents widely applicable to [the] majority of our patients. Some of those agents include BTK inhibitors such as ibrutinib, acalabrutinib, [and] zanubrutinib. Those 3 are covalent BTK inhibitors.

Right now, ibrutinib has been removed from the market for mantle cell lymphoma, but we at least have 2 others, which [are] acalabrutinib and zanubrutinib. More recently, the [Food & Drug Administration] (FDA) has approved a noncovalent BTK inhibitor, which is called pirtobrutinib. Th[ese] are all for patients with relapsed/refractory mantle cell lymphoma.

[There are] other agents, including immuno-modulatory agents, such as lenalidomide. There [are] also [chimeric antigen receptor] (CAR) T-cell therapies. And, the question is, can we use those new agents earlier for patient treatment? Can we incorporate them into frontline therapy?

I[‘d] like to discuss some of our recent studies that was [on] a non-chemotherapy-based combination. One of the example[s] was the SYMPATICO study, which was reported at last year's [American Society of Hematology] (ASH) [meeting]. It's a randomized study phase 3 study. The comparison was to a standard single-agent ibrutinib and experimental comparison was a combination of BTK inhibition with ibrutinib plus a BCL2 inhibitor, venetoclax.

The combination of ibrutinib and venetoclax has [been] shown to have [a] higher complete remission rate and a higher complete remission rate [and] significantly longer progression-free survival. So, improvement of 22-month, 2-year, medium progression-free survival to 32 months. [which is] about [a] 10-month advantage. The way that we look at the combination is that if you have a patient who is getting treatment with a single agent, and they are tolerating it, with maybe partial remission, that one could consider doing the combination [by] adding venetoclax, therefore improv[ing] the response quality, maybe to complete remission, and, hopefully, with [the] extension of progression-free survival.

Source:

Ruan J. Debate - Novel, “Non-Chemotherapy” Approaches Are Best for Initial Therapy for Mantle Cell Lymphoma. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; April 5-6, 2024; New York, New York.