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The combination regimen demonstrated improved efficacy outcomes with a tolerable profile among patients with relapsed/refractory mantle cell lymphoma.
As the treatment landscape continues to grow in the mantle cell lymphoma space, those with relapsed/refractory disease appear to have a promising regimen on the horizon; however, more investigation needs to be done, according to Tycel J. Phillips, M.D.
Phillips — who is an assistant professor at the University of Michigan Cancer Center – sat down with OncLive, a sister publication of CURE, to discuss a new treatment regimen for treatment-naïve patients and those with relapsed/refractory disease, which was presented at the 2018 American Society of Hematology (ASH) Annual Meeting.
Can you give a bit of background on this study and the hypothesis?
Phillips: Mantle Cell Lymphoma is a rare subset of non-Hodgkin lymphoma. It affects about 5 to 6 percent of all patients. It’s typically very common in patients age 65 and older, with a preference of male patients. Currently, we don’t have an official standard of care. A lot of research nowadays is trying to determine an optimal treatment regimen for patients, either in the transplant-eligible or the transplant ineligible population.
As far as chemotherapy regimens, (the combination use of) Treanda (bendamustine) and Rituxan (rituximab) has been shown to be an effective regimen and well-tolerated. And as we all know, in the relapsed/refractory setting, the BTK inhibitors have also shown to be very effective.
In the two arms of this study, one is evaluating the combination of Calquence (acalabrutinib), which is a second-generation BTK inhibitor, plus Treanda and Rituxan in treatment-naïve patients. Also, we’re looking at this in a relapsed/refractory setting to see how the combination affects these patients as well. The hope is that this a very safe and tolerable regimen, but also to improve upon the efficacy of both (Treanda plus Rituxan) versus the BTK inhibitors alone.
What are the next steps of this study?
There is now a phase 3 randomized study looking at Treanda plus placebo versus Treanda plus Calquence. It’s very similar to the former cyclic SHINE study. This phase 3 study is currently enrolling multiple institutions. There are approximately 100 patients enrolled worldwide at this point, and this study will be ongoing for at least another couple of years before the study is completed and for maturation of the data.
Are there any other classes of agents in mantle cell lymphoma being looked at in combination with chemotherapy?
There are other BTK inhibitors being looked at, such as Zanubrutinib. There are also studies looking at Venclexta (venetoclax), which is a Bcl-2 inhibitor, and Velcade (bortezomib), which is a proteasome inhibitor. Velcade has unfortunately not shown the responses we’d hoped for. There will potentially be studies with Revlimid (lenalidomide) in this disease setting.
What are the key takeaways from this study?
The key takeaway point from this study in both the treatment-naïve and relapsed/refractory setting, the combination of Treanda and Calquence appears to be safe and efficacious. The response rates were impressive, but again, they need to be further validated in a phase 3 study. This is another key step in trying to improve and hopefully get an optimal first-line regimen for patients with mantle cell lymphoma. At least in this situation, in patients who are ineligible for autologous stem cell transplantation in the frontline setting.
The key point is that the combination appears to be safe. In what we’ve seen with a lot of these combination studies, Treanda seems to be a very good regimen for combining novel agents with, compared to some of the other regimens due to the overall tolerability of the regimen, at least in the initial short term of treatment. Compared to some other studies, we did not see a significantly high risk of infection with this treatment, which has been some of the criticism lately with Treanda and some of the other subsets of non-Hodgkin lymphoma. Specifically, with follicular lymphoma, there has been a lot of alarm about the number of infections that have occurred in these patients. It appears in this setting that we did not see that. Whether it’s a difference in the patients or their biology, this is something that can be answered later on. I don’t think the study looked at T-cell subsets, a depletion that has been a key indicator of infection in some of these patients. This is also something that can potentially be looked at later.