Michael Wang, MD

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses current and upcoming treatments being investigated for patients with mantle cell lymphoma (MCL).

The Bruton’s tyrosine kinase (BTK) inhibitor LOXO-305, as well as the chimeric antigen receptor (CAR) T-cell therapy JCAR017, look promising in this setting, according to Wang. Another upcoming drug in a currently enrolling trial is VLS-101, a receptor tyrosine kinase-like orphan receptor 1 (ROR1)-directed antibody-drug conjugate from VelosBio in San Diego, California. This treatment has received FDA Fast Track and Orphan Drug designations for patients with MCL.

Wang says cirmtuzumab (UC-961), another ROR1 antibody, plus ibrutinib (Imbruvica) are also being investigated for these patients and have shown high response rates including complete responses. This combination is being looked at by the FDA and received an Orphan Drug Designation this year.

Although Wang is worried about CAR T-cell therapies lagging behind in the MCL setting, this disease has natural susceptibility to intervention and may help the previously discussed drugs to be approved.

<< View more resources and information regarding MCL

Videos

Michael Wang, MD, discusses current and upcoming treatments being investigated for patients with mantle cell lymphoma.

Clinical Trials Look at Promising Treatments in Mantle Cell Lymphoma

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses potential upcoming treatment options for patients with mantle cell lymphoma (MCL), including targeted therapies and chimeric antigen receptor (CAR) T cells.

These treatments include LOXO-305, which Wang says is very effective and will probably be another addition to the therapeutic options in the near future. It is able to reverse Bruton’s tyrosine kinase (BTK) inhibition, similar to the other 3 approved BTK inhibitors which are all reversible, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa).

Wang believes the treatment of MCL has evolved from chemotherapy regimens like rituximab (Rituxan), cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and rituximab plus bendamustine to a targeted therapy and CAR T-cell therapy era.

Brexucabtagene autoleucel (Tecartus), a CAR T agent, being approved is only the beginning for patients with MCL, according to Wang. Many other CAR T-cell studies are being designed for this setting with different mechanisms of action, including on and off switches, peptide insertions, and PD-L1 knockout.

Michael Wang, MD, discusses potential upcoming treatment options for patients with mantle cell lymphoma, including targeted therapies and chimeric antigen receptor T cells.

Exploring Targeted and CAR T-Cell Therapies on the Horizon for MCL

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the role of BTK inhibitors as treatment of patients with mantle cell lymphoma (MCL) ahead of his presentation at the 2020 SOHO Annual Meeting.

Wang believes the overall survival of patients with MCL will continue to be prolonged. The first approved targeted treatment option in MCL was bortezomib (Velcade), which presented with an objective response rate (ORR) of 32%. Lenalidomide (Revlimid) was the second drug to be approved a few years later in 2013, which had an ORR of 25%.

Ibrutinib (Imbruvica) was later approved for the treatment of patients with MCL. Wang says he had the honor of leading the clinical trial that led to this agent’s approval, which had an ORR of 68% and a complete response rate of 20%. Several years later, acalabrutinib (Calquence) was also approved, which had great survival outcomes as well. Zanubrutinib (Brukinsa) was approved by the FDA, marking the third BTK inhibitor approved for the treatment of MCL.

Michael Wang, MD, discusses the role of BTK inhibitors as treatment of patients with mantle cell lymphoma ahead of his presentation at the 2020 SOHO Annual Meeting.

BTK Inhibitors Continue to Improve Survival in Mantle Cell Lymphoma

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the pharmacological profile of KTE-X19 in patients with high- or low-risk relapsed/refractory mantle cell lymphoma (MCL) in the ZUMA-2 trial (NCT02601313).

In this phase 2 trial, investigators wanted to see whether the chimeric antigen receptor (CAR) T-cell expansion would be similar between patients with high-risk and low-risk disease. The results showed the efficacy was the same for these groups. According to Wang, finding that the efficacy was the same for the patients with low-risk MCL is important because there is now underlying data to correspond to the observation that low-risk and high-risk disease react the same with a CAR T-cell therapy such as KTE-X19; therefore, an anti-CD19 CAR T-cell therapy can overcome high-risk resistance in patients. In his opinion, this is powerful data for this setting.

The pharmacodynamic profiles between patients with low- and high-risk MCL were shown in the poster presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program. Wang says there was a small trend between increased cytokines in the high-risk group, but there was not a statistical difference.

<< View more resources and information regarding mantle cell lymphoma

Michael Wang, MD, discusses the pharmacological profile of KTE-X19 in patients with high- or low-risk relapsed/refractory mantle cell lymphoma in the ZUMA-2 trial.

ZUMA-2 Trial Demonstrates Similar Outcomes for High- and Low-Risk MCL

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the approaches physicians can use when treating their patients with mantle cell lymphoma (MCL) who have become resistant to cellular therapies, such as chimeric antigen receptor (CAR) T-cell therapy.

According to Wang, there are numerous options available now, including precision medicine and targeted therapies. Physicians can target, sequence, and biologically study a patient with MCL to decide what the key driver is that is causing resistance to cellular therapy. With this approach, physicians can attack the Achilles heel of each patient&rsquo;s particular resistance mechanisms of the disease.

Following cellular therapy, precision medicine can be used in the future depending on the biology of the disease. Wang says there has never been a better time to be a doctor in the field of MCL, and he shares that it is his dream to cure as many patients with MCL as possible.

Michael Wang, MD, discusses the approaches physicians can use when treating their patients with mantle cell lymphoma who have become resistant to cellular therapies, such as CAR T-cell therapy.

Wang Highlights Treatment Options after Resistance to Cellular Therapies in MCL

Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the potential role for the next-generation Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) compared with first- and second-generation BTK inhibitors for the treatment of patients with mantle cell lymphoma (MCL).

Zanubrutinib is the newest BTK inhibitor to appear in the treatment landscape for patients with MCL, but it does not have significant follow-up time yet, Wang says. There are many interesting points for the role of zanubrutinib in MCL, and it is an active agent, according to Wang. This agent received

priority review from the FDA in August 2019 for the treatment of patients with MCL

who have received at least 1 prior treatment.

Michael Wang, MD, discusses the potential role for the next-generation Bruton&#39;s tyrosine kinase inhibitor zanubrutinib compared with first- and second-generation BTK inhibitors for the treatment of patients with mantle cell lymphoma.

Michael Wang, MD | Authors

Articles

Clinical Trials Look at Promising Treatments in Mantle Cell Lymphoma

Exploring Targeted and CAR T-Cell Therapies on the Horizon for MCL

BTK Inhibitors Continue to Improve Survival in Mantle Cell Lymphoma

ZUMA-2 Trial Demonstrates Similar Outcomes for High- and Low-Risk MCL

Wang Highlights Treatment Options after Resistance to Cellular Therapies in MCL

Fitting Zanubrutinib into the Treatment Landscape for Mantle Cell Lymphoma