Michael Wang, MD

Michael Wang, MD, a professor in the department of lymphoma and myeloma at MD Anderson Cancer Center, gives a brief overview of the safety and efficacy findings of a phase 1b study (NCT02717624) evaluating acalabrutinib (Calquence) plus venetoclax (Venclexta) and rituximab (Rituxan) in patients with mantle cell lymphoma (MCL).

In this ongoing, multicenter, open-label study, 21 patients with MCL were administered the triplet combination to evaluate whether it can improve upon frontline convention chemoimmunotherapy in an elderly patient population.

Findings showed that the combination was safe and well tolerated with the most common grade 1 or 2 side effects including diarrhea, headache, and fatigue. Besides diarrhea, no grade 3 or 4 toxicities were reported and while bleeding occurred in 33% of patients, it was either grade 1 or 2.

 What is striking and noteworthy for this study in that number 1, the combination is very safe. The patients tolerated the therapy very well. There are no toxins deaths. Unfortunately, 4 patients died from COVID without any relationship to our study therapy. The other issue is that the efficacy is very, very high. One hundred percent of our patients responded to therapy, and the complete response rate by PET scan was 90%.

 The study therapy was tolerated very well. The most common side effects included diarrhea, headache, and fatigue, but the majority of those side effects are grade 1 or 2. There's hardly any grade 3 or 4 toxicities except diarrhea.

With ibrutinib, we are always concerned about atrial fibrillation. However, among the 21 patients, none of the patients had atrial fibrillation with the study combination. Bleeding occurred in 33% of patients and they were all grade 1 or grade 2, there were no grade 3 or 4 bleeding. Therefore, there was no severe bleeding.

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Michael Wang, MD, gives a brief overview of the safety and efficacy findings of a phase 1b study evaluating acalabrutinib plus venetoclax and rituximab in patients with mantle cell lymphoma.


Acalabrutinib Triplet Shows Tolerability in Mantle Cell Lymphoma 

Study results may indicate for a potential alternative treatment option to address the unmet needs for elderly patients with newly diagnosed mantle cell lymphoma (MCL), according to Michael Wang, MD.

Wang, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the unmet needs that the triplet combination of acalabrutinib (Calquence) plus venetoclax (Venclexta), and rituximab (Rituxan) looks to fill in MCL.

The safety and efficacy of this combination is currently being examined in the ongoing, multicenter, open-label study (NCT02717624), which enrolled 21 patients with MCL. Experts working on this study believe that the combination could improve upon frontline convention chemoimmunotherapy for this elderly patient population.

Wang noted that future trials require more patients to be enrolled in order to confirm the results. Despite this, the combination was deemed tolerable with high response rates. Additionally, 100% of patients responded to therapy, with a 90% complete response rate by PET scan.

 The unmet needs of this population, which is elderly patients with a newly diagnosed MCL, in the past and until now, internationally, we are treating these patients with chemotherapy. This study gave us a good result with chemo-free therapy that has a very superb safety and efficacy profile. In order to replace chemotherapy, we have tried doublets. We have tried ibrutinib [Imbruvica] with rituximab in the frontline [setting]. We published this article recently in the 

, and the response rate is very high. However, the cardiotoxicity was noted with atrial fibrillation.

 Although the doublet is very efficacious, we think that with the triplicated chemo-free therapy in the frontline [setting], we will have a better efficacy analysis, and hopefully, without severe toxicities. This study just showed that the response rate could be so high and 100%, it cannot be better. The complete response is 90% by PET scan, it can hardly be better. The side effect profile was very tolerable. That's a good study, a wonderful combination with a safety profile and highest response rate that can be attained during the clinical trial. However, I want to note that we only have 21 patients in this trial. And in order to confirm this result, we need more patients in the future trials.

Study results may indicate for a potential alternative treatment option to address the unmet needs for elderly patients with newly diagnosed mantle cell lymphoma, according to Michael Wang, MD.

Triplet Combination Addresses Unmet Need in Small Study Population With Mantle Cell Lymphoma

Michael Wang, MD, a professor in the department of lymphoma and myeloma at MD Anderson Cancer Center, discusses the study design of the ongoing, multicenter, open-label study (NCT02717624).

The study examined the combination of acalabrutinib (Calquence) plus venetoclax (Venclexta), and rituximab (Rituxan) in patients with treatment naïve mantle cell lymphoma (MCL) who are unable to receive chemotherapy.

The target enrollment for the trial was 20-30 patients with MCL who had not been treated prior and the number of patients with treatment emergent adverse events was the primary end point. Participants were given acalabrutinib between day 1 of cycle 1 at 100 mg until disease progression or intolerance, venetoclax on day 1 of cycle 2 with dose escalation through cycle 5 to 25, and rituximab on day 1 of every cycle for 6 cycles followed by every other cycle until cycle 24.

 The study was designed to enroll 20 to 30 patients with MCL who never treated it before. The primary end point is the safety analysis, and the secondary objectives include efficacy, complete response, partial response, and overall response. Acalabrutinib was given from cycle 1 day 1 at 100 mg BID, until disease progression or intolerance. Venetoclax was given on cycle 2 day 1 with a 5 week ramp up period of dose escalation through cycle 5 to 25. Rituximab was given on day 1 of every cycle for 6 cycles and then after that, every other cycle until cycle 24. So, this is how dose limiting toxicity was assessed from cycle 2 day 1 to cycle 3, day 2.

Michael Wang, MD, discusses the study design of the ongoing, multicenter, open-label study examining an acalabrutinib triplet in MCL.

Phase 1b Study Examines Acalabrutinib Triplet in MCL

Michael Wang, MD, professor in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center, discusses the growing awareness of chimeric antigen receptor (CAR) T-cell therapy among community oncologists and patients with mantle cell lymphoma (MCL).

CAR T-cell therapies modify the patient’s T cells to target the CD19 protein expressed in cancer cells, which can lead to long-term remission in patients with advanced MCL, according to Wang.

CAR-T cell therapy using brexucabtagene autoleucel (Tecartus) was approved in July 2020 for patients with relapsed or refractory MCL, based on the ZUMA-2 clinical trial led by Wang. In the trial, 87% of patients had a response to CAR T-cell therapy and 62% had a complete response. While CAR T-cell treatments have a high toxicity, the study showed that it can be balanced to achieve remission.

According to Wang, some oncologists continue to use other therapies in advanced MCL, which including autologous stem cell transplant and chemoimmunotherapy. However, he says that awareness of CAR T-cell therapy is spreading. Community oncologists are now better informed about its efficacy and safety, and in addition, patients and their families are seeking out specialists when they learn about the availability of the therapy.

 Since the approval a little more than a year ago, I have started receiving referrals from the community oncologists for their patients to be considered [for] CAR T-cell therapy. I think yes, there are still oncologists using the older therapies. But I think the knowledge gap is closing very rapidly and everybody has heard about the CAR T cells. Sometimes, before the doctors realize, the patient already requested it, and the patient is in a very educated population. The patient, and very likely their young families, are searching the computer, Google, the web, all the time for knowledge of MCL, [for] new therapies, and [they have] contacted people like me and other doctors for us to see their family members with MCL. I really think that [news of] the CAR T-cell therapies’ efficacy and safety will continue to spread, [and] the usage of it will continue to rise. So I think the future is bright.

Michael Wang, MD, discusses the growing awareness of chimeric antigen receptor T-cell therapy among community oncologists and patients with mantle cell lymphoma.

Raising Awareness of CAR T-Cell Therapy for Advanced MCL

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.

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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.

Michael Wang, MD | Authors

Articles

Acalabrutinib Triplet Shows Tolerability in Mantle Cell Lymphoma

Triplet Combination Addresses Unmet Need in Small Study Population With Mantle Cell Lymphoma

Phase 1b Study Examines Acalabrutinib Triplet in MCL

Raising Awareness of CAR T-Cell Therapy for Advanced MCL

Clinical Trials Look at Promising Treatments in Mantle Cell Lymphoma

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