Factors for Consideration in Treatment Decision-making for MCL

Anthony R. Mato, MD, MSCE: I want to switch gears to Michael for a second because I think there may be a little bit less consensus in the mantle cell lymphoma (MCL) community as there might be even in the CLL (chronic lymphocytic leukemia) community about frontline therapy. Michael, could you weigh in? Specifically, I've heard you, in the past, talking about [how] chemotherapy-free is kind of the future for MCL. Would you also weigh in about that in the context of the frontline [setting]?

Michael Wang, MD: Anthony, it is totally true that, [in] MCL, there's a lack of a consensus. The lack of consensus is because MCL is even more rare than CLL, so phase 3 trials [are] very hard to conduct. Most of our standard therapies are based on phase 2 trials, and I totally agree with Dr. Danilov on what he has stated on MCL. Basically, [in] MCL, we divide them into elderly patients [aged] over 65 [years] and then young patients [aged] less than 65 [years]. For younger patients [aged] less than 65 [years], the traditional therapy has been the Nordic therapy, which is 6 cycles of induction therapy followed by autologous stem cell transplant, and this was mainly set on a few phase 2 clinical trials. This therapy has been here for over 20 years. [For] over 20 years, everybody [has] known [that] the chemotherapy is too high. You have to rescue that with autologous stem cell [transplants].

Like Dr. Danilov indicated, at [The University of Texas] MD Anderson [Cancer Center, they] use 8 cycles of hyper-CVAD (rituximab and cyclophosphamide, vincristine, doxorubicin, and dexamethasone), but hyper-CVAD is also very intensive. It's the most intensive therapy you can deliver to a human short of a stem cell transplant. These 2 therapies are over 20-something years [old], and the secondary malignancy rate after the patient [is] in remission for a number of years is very high.

At [The University of Texas] MD Anderson [Cancer Center], we do window 1 and window 2 clinical trials. A window 1 clinical trial is already in the NCCN (National Comprehensive Cancer Network) guidelines. By the way, hyper-CVAD is also from a phase 2 publication, single center for viral center. You don't see a lot of phase 3 [trials]. Another phase 2 window study uses ibrutinib/rituximab followed by hyper-CVAD, followed by maintenance, but that's window 1. Like you said, Anthony, we are moving away from chemotherapies to chemotherapy-free therapies. Ideas like the window 2 clinical trial where, instead of the ibrutinib/rituximab in the first window period, we added a manual cost to it. [With] a lower response rate of 96%, CR (complete response) is very good. It's at 92%. After that, patients [with] low-risk [disease] would not receive any chemotherapy. [For] high-risk [disease, we do] 4 cycles, and then you have intermediate [disease] at 2 cycles.

We are, stepwise, using clinical trial data to try to get rid of chemotherapy. A window 1 study published last year. This is for the younger patients, but [in] older patient, we use chemoimmunotherapies, rituximab/bendamustine, R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone) and VR-CAP (rituximab, cyclophosphamide, doxorubicin, prednisone) in all this. [For older] patients, there's a big [difference compared to] young patients. They can live more than 10 or 12 years for the autologous stem cell transplant, hyper-CVAD at 30 years. They are living over 10 years, but [older patients] live only about 5 years if you give the R-CHOP or rituximab/bendamustine. There's a big discrepancy: 10 years vs 5 years. In order to close this gap, we added ibrutinib to bendamustine/rituximab. Everybody knows that progression-free survival is 6.7 years. Some people said, "Michael, why don't you do BPR followed by ibrutinib sequential?" Let me tell you, in the SHINE clinical trial (NCT01369069), among 183 hospices and hospitals in the world, one-third of the patients did not make it to the second line [of therapy] due to various reasons. They are getting old, there are insurance issues, [and] many, many issues.

In most cases, MCL in the [older] patient is a 1-shot disease. You only have 1 shot. When the patient come here, I will definitely deliver the therapy with the longest support working for his survival, giving them the head start so that 6.7 years [later], they do not need any therapy. They would all probably survive 10 years, so this is very important. A lot of people read the SHINE presentation, but this is not even in the presentation. You have to read the paper; you have to understand the disease. I think the panel would agree with me that those caveats are very important.

Anthony R. Mato, MD, MSCE: Michael, point-blank question then to any clinician who's sitting out there listening to us talk today: if they're thinking about giving bendamustine/rituximab, if that's their standard approach for an individual patient, do you think there's any justification to give bendamustine/rituximab alone, or should it be combined with ibrutinib based on the data?

Michael Wang, MD: If the patient doesn't have comorbidities like atrial fibrillation, dilated heart, low ejection fraction, COPD (chronic obstructive pulmonary disease) with frequent pneumonia, I would use the rituximab with bendamustine/rituximab plus ibrutinib. This is not showing up in the guidelines. I'm sure it will, but I think that the SHINE study is the new global standard, in my opinion, but you have to be careful with the toxicities.

Anthony R. Mato, MD, MSCE:Thanks so much.

Transcript has been edited for clarity.