Advancements on the Horizon in Mantle Cell Lymphoma

EP: 1.Disease Overview: Mantle Cell Lymphoma

EP: 2.Factors for Consideration in Treatment Decision-making for MCL

EP: 3.Mantle Cell Lymphoma Maintenance Strategies

EP: 4.Second-line Therapies in MCL: Regimens With BTK Inhibitors and BCL-2 Targeting Therapies

EP: 5.BTK Inhibitors in Relapsed/Refractory MCL and Treatment Selection

EP: 6.CAR T-Cell Therapy in R/R MCL

EP: 7.Strategies for Sequencing and Combining Therapies in MCL

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EP: 8.Advancements on the Horizon in Mantle Cell Lymphoma

EP: 9.Treatment Overview: Chronic Lymphocytic Leukemia

EP: 10.Acalabrutinib in CLL: Insights from the ELEVATE TN and ASCEND Trials

EP: 11.Zanubrutinib in CLL: The ALPINE Trial

EP: 12.Treatment Decision-making Among Second-generation BTKis in CLL

EP: 13.Updates from Patient-reported QOL and Matching-adjusted Indirect Treatment Comparisons (MAICs) Studies in CLL

EP: 14.Emerging Approaches in CLL

EP: 15.TRANSCEND CLL: CAR T-cell Therapy for CLL

EP: 16.The Potential Role of Venetoclax Combination Approaches in CLL

EP: 17.Considerations for COVID-19 in MCL and CLL

EP: 18.Anti-CD20 Regimens and Triplet Therapies in CLL

EP: 19.Pirtobrutinib and Other Non-Covalent BTK Inhibitors in the Treatment of CLL

EP: 20.Closing Remarks on Upcoming Data and Future Perspectives in MCL and CLL

Anthony R. Mato, MD, MSCE: Alexey, I'm going to round out the mantle cell lymphoma (MCL) section because we could go on and on talking about this all day. There's so much new, but we're sort of roaring into a new era here. That's my attempt at a bad joke. Can you comment at ROR1 as a target? There [are] a few different approaches that are being developed: antibody-drug conjugates (ADCs), naked antibodies, small molecule inhibitors, [and] CAR (chimeric antigen receptor) T[-cell therapy]. There’s a list. What's likely to be our first agent available to patients? Can you describe the data to support its use or not?

Alexey V. Danilov, MD, PhD: ROR1 is within the Wnt signaling pathway. It's expressed on MCL cells and CLL (chronic lymphocytic leukemia) cells as well. It seems so far [that] the best data with ROR1 targeting agents comes from MCL studies. Like you said, [there are] multiple strategies. There are ROR1 targeting CAR-T cells emerging, as well as naked antibodies, [and] ADCs. VLS101 has a very good data with 50% response rate and multiple effects in MCL. A recent study presented at [the 2022] ASCO (American Society of Clinical Oncology) [Annual Meeting] combined ROR1 targeting antibody with ibrutinib with a median progression survival rate of 36 months. Although [this is only from] a small number of patients, this is promising in direct comparison to BTK (Bruton tyrosine kinase) inhibitors alone. We will certainly need more data on these agents. Right now, the data [are] still very limited. All of these agents are being developed. It seems that the ADCs have the most data so far and [are] going to proceed with the large phase 2 study, so we'll see what the data shows.

Anthony R. Mato, MD, MSCE: Final question for MCL. I want Alexey, Michael, and Brian to limit yourselves to a 1-word answer, if possible. Speaking to agents that are not yet approved, what is most exciting to you as of 2022? One word. Brian?

Brian T. Hill, MD, PhD: Pirtobrutinib.

Anthony R. Mato, MD, MSCE: Michael?

Michael Wang, MD: Pirtobrutinib.

Anthony R. Mato, MD, MSCE: Oh, this is easy. Alexey?

Alexey V. Danilov, MD, PhD: Bispecific.

Anthony R. Mato, MD, MSCE: Got it, okay.

Transcript has been edited for clarity.