← The Fellow on Call: The Heme/Onc Podcast
The Fellow on Call: The Heme/Onc Podcast
Episode 138: Follicular Lymphoma Series, Pt 3 - Relapsed/Refractory Management (non-cellular therapy options)
Ronak Mistry, Vivek Patel, Dan Hausrath
Loading summary
Transcript31 lines
- [00:00]
A
Hey, friends. This episode of the Fellow on Call is not meant to be used for medical advice and is intended for educational purposes only. Patient information has been modified to ensure privacy. The views expressed in this episode do not necessarily reflect the views of our employers. Enjoy. Welcome to another episode of the Fellow on Call, the hemonk podcast. We're coming at you from Rouleau University Medical Center. I'm Ronuk.
- [00:23]
B
I'm Vivek.
- [00:24]
C
And I'm Dan.
- [00:26]
A
And in today's episode, we continue on our follicular lymphoma journey, this time talking all about maintenance and relapse refractory disease and how we approach these patients.
- [00:36]
B
Really excited to get into this. As our listeners may have noticed, we've taken some time off from recording. We published a paper in the jco, had an ASCO presentation, showed that the Fellow on Call is a gold standard part of curriculum for fellow education in hematology oncology. And. And we've really done a lot to revamp how we're going to have our podcast move forward. So really get excited. Over the next year you're going to see a lot of new things coming from the Fellow on Call.
- [01:02]
C
That was nice of them to cover for me, but the real reason is I just ghosted everyone for like three months. So sorry about that, y'.
- [01:08]
B
All.
- [01:08]
A
Yeah, whatever. And Dan's out there living his best.
- [01:11]
C
Life, just big time and people constantly. But yeah, we got a lot of good stuff to cover today, so let's get into it.
- [01:15]
A
Yeah, that sounds good. Without further ado, let's roll that show. Guys, I'm so excited to be back. Today we're continuing our discussion about follicular lymphoma. In the first couple of episodes we talked about the nuts and bolts, we talked about first line treatment and today we get to talk about maintenance and relapse refractory disease. So, Vivek, do you want to start us off with the case?
- [01:40]
B
Yeah. So we have a six year old female who presented a clinic with fevers, night sweats and a 10 pound unintentional weight loss. She had noticed cervical and axillary adenopathy a few years ago that recently started to enlarge. She had CT imaging which showed adenopathy above and below the diaphragm. She was then sent from her primary care provider to ENT who performed an FNA which showed a CD10 positive monotypic B cell population without increased forward scatter concerning for possible follicular lymphoma. PETCT demonstrated moderate to intensely avid adenopathy with the Highest SUV measuring 10.5 in her right axill as well as diffusely avid bone marrow uptake. She underwent excisional right axillary node biopsy given that it was the highest SUV which confirmed classic follicular lymphoma that on the report was noted to be former grade 3A per older who criteria. Her labs were notable for mild anemia with a hemoglobin of 10 and an LDH elevated at 300. So before we get into her management, can we recap Frontline management of follicular lymphoma Remember from our last episodes that.
- [02:49]
A
It'S really critical to confirm that there's no evidence of histologic transformation to dlbcl, which means that this requires an excisional biopsy and a PET CT can help guide what to biopsy based on the highest SUV uptake. You will see former grading written on some of these reports. But now we mainly have classic follicular lymphoma which used to be called grade 1 to 3A. We have follicular large B cell lymphoma, formerly called grade 3B and then we have overt transformation to large B cell lymphoma. Next we determine if the patient has stage one disease, asymptomatic stage two to four disease or symptomatic lymphoma. Remember that for stage one disease the options are observation versus definitive radiation, which are both reasonable options as roughly 30 to 40% of patients will follow a very indolent course and will never actually need treatment and there is also no difference in overall survival there. So the reality is why would you subject these patients to unnecessary treatments and toxicities? For asymptomatic patients that are stage two to stage four, observation versus rituximab monotherapy are both reasonable options and we discussed this in our last episode so go check that out. Roughly one third of these patients never need treatment with observation and this improves to 50% of patients not needing subsequent treatment if they receive rituximab weekly for for four doses. And again there was no difference in overall survival. For symptomatic patients we can utilize Bendamussine rituximab or revlimid rituximab also known as that R squared regimen and this is reasonable showing non inferiority and less toxicity compared to regimens like R chop chemotherapy.
- [04:34]
B
So this patient had clear symptomatic advanced stage disease and was treated with BR for six cycles, remember? So in this case there was that avid bone marrow and a lot of people might think do I need to do a bone marrow biopsy here. But remember that bone marrow biopsy is not required in these patients as it would not change management in most cases. You know, if you had that stage one patient who you were going to do definitive radiation for curative intent, and maybe you wanted to make sure there was no bone marrow involvement, it's reasonable. But for these advanced stage cases, it's an unnecessary procedure and it won't change your upfront management. Because this patient needs chemotherapy, she gets a PET CT at the end of treatment. After the six cycles of Bendamustine Rituximab which showed significant decrease in the avidity of her adenopathy with a Deauville score of 3. She mentions that she had read about rituximab maintenance on the Internet. So what's the data behind rituximab maintenance after the first line of therapy?
- [05:28]
A
That's a great question. So, quick aside on response assessment in lymphoma, which we covered in our DLBCL series because this is relevant to this conversation. So remember that the Doval score, which was named for that meeting in Deauval, France, or the Lugano score, named for that meeting that happened in Lugano, Switzerland, is a five point scale that is critical to determine if the patient has a complete response to therapy. It's common to have some residual adenopathy at the end of treatment, but this may just truly be dead tissue rather than active lymphoma. The PET CT scoring helps to assess for residual disease and a score of 1 to 3 is consistent with a complete response. A score of 4 out of that 5 point scale is indeterminate and a score of 5 is highly concerning for refractory lymphoma. And this is based on comparison to the avidity of the mediastinal blood pool and the liver. And it's really important in follicular lymphoma to not ignore refractory disease with a score of 5 and to consider repeat biopsy as there may have been an underlying transform component that was missed. So your question about Rituxan maintenance. So for Rituxan maintenance there was a phase 3 randomized control trial called the Prima trial and this included over 1000 patients and they were randomized to Rituxan maintenance every two months for two years versus observation after frontline treatment with chemo immunotherapy. The six year follow up showed improved progression free survival with rituximab maintenance at 59% versus 47% and there was no difference in overall survival. The nine year extended follow up was published in 2019 in the JCO which we'll link in our show notes. But in this they included 600 patients who agreed to extended follow up from the original cohort. The median progression free survival in the Rituxan maintenance arm was 10 and a half years versus 4.1 years in the observation arm. And remember that though not all relapses in follicular lymphoma need to be treated, if the patient is asymptomatic and progression free survival might have just picked up mild growth in the adenopathy, the percentage of patients not requiring lymphoma treatment at 10 years was 53% versus 41% favoring that Rituxan maintenance arm. And there was no difference at all in overall survival or transformation to large cell lymphoma.
- [07:47]
B
So, Rona, you know a couple things that I want to mention of what you said that is confusing when you look at follicular lymphoma literature in particular is one, we have this PFS endpoint and for every other cancer, we're obsessed with PFS as progression free survival composite ENDP. Here you mentioned the median was 10.5 years versus 4.1 years. Anytime you see that gap of a difference, unless it's a truly transformative therapy, you should think about maybe it's that arm with a really, really long median PFS. Maybe it was hovering just above the 50% line. And because of that it's an exaggerated large difference in progression free survival because the median doesn't necessarily mean anything. The second important thing, and that's just a critical analysis point, but the second important thing here is that when we have these patients in follicular lymphoma, the bigger question is to next lymphoma treatment. If you relapse in lymphoma, it's quite heterogeneous. You don't always need to treat it. So the difference in time to next lymphoma treatment is a much more important endpoint and more pragmatic when it comes to the patient in front of you. What you mentioned there is that we have about a 10% improvement at 10 years. So you're getting a 10% improvement for patients coming in every two months for two years with rituximab maintenance therapy. But it's not changing the trajectory of the disease. So the decision to pursue maintenance is really individualized with the patient in front of you. Some patients say I will do anything to delay the time to next treatment. And rituximab maintenance would be something to do that. However, it comes with time. In the infusion clinic, there is double the rate of severe infections. You know, they're very uncommon, but still there's double the rate of severe infections in the Rituxan maintenance arm. So it's just something to consider for these patients whether all patients need maintenance. That really went away in the era of COVID Now that we've come out of COVID it's really up to the patient and the discussion with the patient. No clear cut answer. But the important thing for them to know is that there's a 10% improvement. That 10% absolute improvement in needing lymphoma therapy at 10 years, meaning a majority of patients still don't need therapy at 10 years.
- [09:48]
A
Great point and also great reminder about how to critically appraise this literature. Super important. So, Vivek, where did we go from here with this patient?
- [09:58]
B
She decided to pursue rituximab maintenance as she wanted to do anything to delay the time to next treatment and to maximize time with her children and grandchildren without needing that next lymphoma therapy. She completed rituximab maintenance. So two years of Rituxan maintenance and subsequent CT imaging showed ongoing CR. She heard about this thing called pod24 or pod24 in her online Reddit group and asked about what that meant and if this applied to her. So, Dan, can we go through the prognostic role of progression of disease within 24 months, also known as POD24?
- [10:33]
C
Absolutely. As we talked about in our first episode in this series, prognostication, follicular lymphoma is not as clear cut as it is in DLBCL with the IPI score. That IPI score, the Flipi or Flippi score, was developed in 2004 in the pre rituximab era. It provides some prognostic information, but it's not good enough to use when we're counseling patients. Refined models, including the Flippy 24 and the Prima PI are better but still have limitations and are more useful for clinical trials rather than individualized patient counseling. They don't really influence our management. The biggest prognostic factor in follicular lymphoma is the progression of disease within 24 months of the start of treatment with chemo immunotherapy. This concept of POD24 progression of disease24 is by far the most important prognostic factor for our patients. Pod24 was defined by a retrospective study using a cohort from the National Lymphocare database. Including over 500 patients and was published back in 2015 in JCO. All patients were treated with R chop so rituximab era. The investigators chose progression of disease 24 months. Given the consistency across clinical trials that roughly 20% of patients progress at this time point regardless of rituximab maintenance. The 5 year OS was 50% in pod 24 patients compared to 90% in those who did not have progression disease at 24 months. This group of patients represents an important high risk population in follicular lymphoma which likely has now improved with bispecific antibodies in CAR T cell therapies, but it's still an important cohort. Historically, these patients were treated with second line chemo immunotherapy and consider for consultative autotransplant. It's really important to counsel these patients that the most important prognostic factor is if the lymphoma relapses within that first 24 months of the start of chemo. We also want to point out that this is not progression of disease within 24 months of rituximab monotherapy, but a true honest to goodness trial of chemo immunotherapy, something like R CHOP or bentamustine rituximab that BR regimen. And we'll have a link to this study in our show notes as well.
- [12:39]
B
So for our patient, she fortunately did not have pod 24. She did well after her tuxed maintenance, remained in a CR and she underwent routine monitoring with initial Q6 month follow up and then annual follow up with CT surveillance omitted at the four year mark given stability. So a lot of people ask, how often do I need to image these patients? It's very individualized with the patient. You can image them for a couple of years maybe. And if you have stable disease, stable disease, no growth, no growth, you can just do it based on clinical exam and symptoms. You can examine their adenopathy. So imaging these patients forever is definitely not necessary. You can use it, have a discussion with the patient, they have high anxiety, maybe you're gonna scan them a little more frequently so they can know what their disease is doing. Very individualized and very much important to discuss that with the patient that it does not necessarily improve their overall survival because at the end of the day we're gonna treat them if they're symptomatic and you should get imaging in response to a change in symptoms or clinical exam. So she's now six years out from initial treatment and develops drenching night sweats. With back pain. She had palpable axillary adenopsy in clinic and we order a PET ct. Given our high concern for relapse disease, she has confirmed relapse disease with bulky retroperitoneal adenopathy measuring 7 cm and remember tumor bulk and lymphoma is generally around that 7 cm mark and axillary adenopathy measuring 3 cm with a maximum SUV of 9 in both areas. Remember, we got this PET CT again to really think what do we need to biopsy the highest SUV because we still could have a transformed large B cell lymphoma. Here she has an excisional axillary node biopsy to rule out the transformation, which confirms relapsed classic follicular lymphoma. So relapsed classic follicular lymphoma is a very heterogeneous disease which makes it very challenging to treat. It's not one size fits all. Before we get into our case with a patient who had clear symptomatic and more bulky disease, what are treatment options in the relapse setting for low burden disease? Relapse with minor symptoms and for example like groin discomfort from an inguinal lymph node adenopathy enlarging close to the ureter, for example, Maybe they're not symptomatic but it's in kind of a sensitive area. Or what about an older frail patient that may not be able to tolerate some of these more intensive therapies? How do we approach these patients?
- [14:52]
A
So once again, it's not a one size fits all. So not all patients with relapsed follicular lymphoma actually need to be treated if they're asymptomatic. For instance, it is reasonable to consider single agent anti CD20 therapy with either rituximab or obinutuzumab for older patients or frailer patients or those with minimal disease burdens. Remember that rituximab is the original immune therapy and it is a type 1 antibody with a large amount of complement dependent cytotoxicity. There's less antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cellular cytotoxicity. Obinutuzumab is a type 2 antibody with increased antibody dependent cellular cytotoxicity, phagocytosis and direct cellular cytotoxicity and it has less complement cytotoxicity. The thought was that this improved antibody would be more effective than Rituxan therapy and in general it seems that obin has higher rates of infusion related reactions and infections likely due to more significant B cell depletion. Additionally, there are two additional infusions in the first cycle of therapy with obintuzumab compared to rituximab which is often given monthly, particularly when combined with chemotherapy. So there was a Phase 2 randomized controlled trial in relapse follicular lymphoma that compared rituximab to abinutuzumab and this was published in the JCO in 2015 and we'll of course link that in our show. Notes. In this study there were 150 patients that were randomized. There was improved overall response rates at 45% versus 27% but no difference in progression free survival or overall survival when comparing obinutuzumab to rituximab. Notably few patients were rituxan refractory but it seems that there are high response rates with obinutuzumab but it does not translate into improved overall disease control. That is why it's reasonable to use either agent. But often obinutuzumab is preferred to improve those response rates. And also remember good old radiation therapy is very reasonable for palliation or local control of disease, such as for instance when Vivek mentioned perhaps this adenopathy is in a sensitive area without overt progression systemically you can still use radiation in these situations.
- [17:11]
C
It's so important to understand the difference between rituximab and obonutuzumab. You think anti CD20 antibody, what interchangeable, right? Well there are these subtle differences. You also might have patients who can't tolerate one but can tolerate the other. So if they're not tolerating rituximab, openutuzumab is a very reasonable alternative with a potential lower risk for reaction given that it's a humanized antibody rather than a murine antibody. So let's get back to our case. We have a patient who has seen BR and rituximab maintenance and then relapses six years out from treatment. What would be our thoughts on next line of treatment for her?
- [17:45]
B
So this is something that's changed over the years. So you'll see some patients who may have relapsed, I don't know, six, seven years ago and they were retreated with chemo immunotherapy because that's what was being done at the time. And so chemotherapy with R chop, an anthracycline based treatment, would have activity here. Retreatment with bendamussy and rituximab has activity, but the important thing to know is that these are toxic therapies and they have really high risk and real risk that you may one day develop a secondary leukemia, have more lymphodepletion of your B cells, higher risks of infections. And it's also important that we want to save that anthracycline containing regimen for patients because they may transform into large B cell lymphoma. This happens in 7 to 10% of patients with follicular lymphoma. So we don't want to jump towards chemotherapy again if we don't really need to. So what are the other options in this case? So in the relapse setting, some advocate in general for using obinutuzumab plus something else rather than rituximab for what Ronak said with that improved response rate. But we'll talk about the nuances in that. And for right now, I'm going to focus on the best prospective phase three evidence, which is rituximab combination therapies. We had discussed the use of lenalidomide, often called by the brand name Revlimid, for the R squared regimen in the frontline setting. In our frontline episode, this has excellent activity in the relapse setting and much less toxic with lower risk of things like secondary leukemia than traditional chemotherapy. There's a phase three randomized trial called AUGMENT published in the JCO in 2019. There were over 350 patients randomized to rituximab monotherapy plus placebo versus rituximab plus lenolidomide. It was kind of an interesting study because there was a rituximab monotherapy arm. The rituximab was given weekly for four doses in cycle one and then monthly for cycles two through five. So a little bit different than just monthly rituximab when combined with something like a bendamustine chemotherapy. Lenalidomide was given at 20mg, three weeks on and one week off for one total year. It's important to note in this population, only 17% were refractory to their last line of therapy, but it was a high risk population with about half the patients experiencing progression of disease within 24 months. There was improved overall response rate with Revlimid plus rituximab versus rituximab alone at 78% versus 50% and improved CR rate at 34% versus 18%. So you're getting a third of patients getting a CR with Revlimid plus rituxeimab and a vast majority of patients getting a good response. There was improved progression free survival with a median of 39 months in the Revlimid rituximab arm versus 14 months in the rituximab monotherapy arm. You might want to check out our myeloma pharmacology episode to learn a little bit more about the toxicities associated with lenolidomide. But remember, we have rash as a potential side effect. Cytopenias are something that that's important to consider. And the other thing that's really important to note is that some patients just get really tired. You know, it comes with a lot of fatigue and you may need to dose reduce from that 20 down to 15 or 10. And also remember that it's renally cleared. So there is a dose adjustment that needs to be made based on creatinine clearance. It's not contraindicated if your creatinine clearance is less than 60. But if the patient has a creatinine clearance between 30 to 59, we'll start at 10 milligrams, half the dose for that patient, which was done in the study. Another option in the second line setting. So we talked about now how revlimid plus rituximab beat rituximab alone. Can one of you talk about the triplet therapy of tafecitumab plus lenalidomide plus rituximab? And I know this was presented at ASH 2024 for that phase three randomized control trial called in mind.
- [21:26]
C
Yeah, great name for a study, by the way. So Ash 2024, like you said, they presented this data and it was using a drug called Tafacitamab. It's a humanized monoclonal antibody against CD19 that works through antibody dependent cellular cytotoxicity, phagocytosis and direct cellular toxicity, but not complement dependent site toxicity like the anti CD20 agents we've talked about. So again, that sort of type 2 antibody, more like Oban, it's given weekly for three months and then every two weeks for nine months after that. The rituximab and lenalidomide follow the same protocol as was used in the Augment trial. So that arm was just like the Augment trial. And the study was designed as a double blind placebo controlled trial of tafecitumab plus R squared versus R squared plus placebo. So they're just adding this onto that R squared protocol. Over 500 patients ended up getting randomized for this trial. And unlike the augment trial, about 40% of the patients were refractory to prior anti CD20 therapies, representing a really high risk population. Only 17% were refractory to their last regimen in the Augment trial. Median progression free survival was improved with the triplet at 22 months versus 14 months in the R squared alone or R squared plus placebo arm. Keep in mind that the Median PFS was 39 months in the Augment trial. Now you might notice that the R squared alone or R squared plus placebo arm in this was 14 months where in the augment trial that PFS was 39 months. This likely reflects that more patients who are refractory to their prior anti CD20 are included in this study. So again, a higher risk population than we were seen before. That's where that disconnect is coming from. But the CR rates were also improved with this triplet regimen at 50% versus 40% in the R square plus placebo arm. So technically this improves PFS. But this regimen is pretty cumbersome with weekly infusions followed by every two weeks for a year in total. Remember, it's three months of weekly and then every two weeks for that remaining nine months. And we also now have very highly active bispecific antibody therapies that are approved in the third line setting with some more coming into the second line space that we'll talk about in our next episode. So hard to, I mean, it's impressive data to be sure in a high risk group, but hard to say. You know, is this practically something that we're going to be seeing a lot of use for if we're having these other therapies that are so highly active on the horizon as well?
- [23:52]
B
And it really, you know, it seems like it's a double edged sword to have more options in the relapse setting for follicular lymphoma with all these regimens, there hasn't really been an overall survival benefit to these routes because there's so many. You can just do the next option again after the patient relapses and just keep on going, which is good for our patients. But it makes it challenging to know exactly which one to choose. It's very individualized to the patient. When you think about if you were to ask somebody, when would you Give Revlimid Rituximab vs adding the Tafecitumab onto that regimen? It's very hard now in 2025 to say, I'll do that. For a lot of patients, you know, it has to be a highly motivated patient who really, really values that PFS benefit. Maybe they were refractory to their last anti CD20. You might consider it. But even in that scenario you're likely going to reach for bispecific therapies, which we'll talk about in our next episode. Before we move on further. In this episode, what about the use of obinutuzumab with lenalidomide in this relapse setting? We talked about obinutuzumab might having a little bit more bang for your buck. So has there been any data in this space?
- [24:52]
A
Yeah, I mean, another thing you may see is the use of obinutuzumab as the preferred agent in combination regimens in the relapse setting. If the patient has previously received rituximab though there's no definitive evidence to support this practice in prospective phase three randomized controlled trials. Essentially we are thinking they've already seen Rituxan. Why would you give Rituxan again? So there was a phase 2 single arm study called the Galen study that looked at obinutuzumab plus lenalidomide followed by obinutuzumab maintenance which we'll link in our show notes. The major downside to this regimen is that it's 18 months of lenalidomide and a two year obinutuzumab maintenance. This increased time on therapy is likely excessive in the era of bispecific antibodies. It would be reasonable to truncate this regimen if it's used in practice to omit the second year of maintenance of binutuzumab. There is a higher risk of infection with this prolonged maintenance and the two year progression free survival in the study was 65% which is similar to the augment study that focused on lenalidomide and rituximab, which is much less time on therapy.
- [26:00]
C
Awesome. Thank you for going over that. Our patient was treated with lenalidomide and rituximab and did very well for four years. She's now coming back again with symptomatic decline, disease relapse. We have a bispecific antibody therapy and CAR T cell therapies now approved in third line setting. We'll discuss that data in our next episode. But let's say for the sake of the flow of this episode that she's not interested in these new therapies and that she's heard about a different chemo pill that could Help. What's the data behind this? I assume she's alluding to oral tazemetostat in follicular lymphoma. What's the data behind that?
- [26:34]
B
So prior to these cellular therapies, which again, we're gonna have a whole episode to really focus on those because they're so critically important, particularly in foll follicular lymphoma. There was also another oral drug other than this tazemetostat that I'm going to talk about that were pi3 kinase inhibitors. And they've been subsequently taken off the market due to limited efficacy with significant toxicity in most of these trials. What you're seeing is the comparator arm is rituximab alone or obinutuzumab alone, and that still has good efficacy in our patients. We have to keep in mind that those Single agent Anti CD20 agents can still be very powerful. We now still currently have approved an EZH2 inhibitor called tazemetostat. EZH2 is an epigenetic regulator and roughly 20% of follicular lymphoma patients have an activating mutation in EZH2. So this drug was really created to target that activating mutation and to affect the epigenetic environment. There was a single arm phase 2 trial that included both mutated and wild type EZH2. As the thought was, the drug would have activity through epigenetic modification. In either case, there were 99 patients who were enrolled with 45 of these patients having an EZH2 mutation and 54 patients who had EZH2 wild type, so no mutation. The overall response rate was 70% in the mutated cohort and 35% in the wild type cohort. So remember that 35% is what we would expect with like an anti CD20 agent medium. PFS was around 12 months. Regardless of mutation status. The drug was extremely well tolerated with minimal side effects. And it can really be a good palliative option for some of our patients. This led to the approval for all comers, regardless of EZH2 mutation status for tazemetostat as a single agent. And it's important to know that, you know, if somebody has already experienced progression through an anti CD20, this could be an option if they're not interested in the bispecific antibody therapy or potentially CAR T therapy. So it provides another oral option.
- [28:30]
A
Thanks for going through that, guys. I think that this is a really good place for us to wrap up this episode so we could dedicate a whole episode to bispecifics and CAR T, because frankly, we've been alluding to it a lot. So we'll discuss the data, the possible scenarios where we may use one over the other in a future episode. So be on the lookout for that. And we'll also be discussing some emerging data about the use of these therapies in the frontline setting because that has also been some really promising data that's coming down the pike. But to close out this episode, any final thoughts that you guys have?
- [29:03]
B
I think one thing that's really important is remember that these relapses are heterogeneous. It's a very heterogeneous disease with an overall favorable prognosis and definitely not one size fits all. Remember that we can use Single agent anti CD20 agents. We can use radiation in some cases, or even observe patients at relapse. And just listen to the details that we discussed in this episode. Just because you have an FDA approval for a triplet like tafecitumab, lenalidomide, rituximab, doesn't mean you have to give that to every patient.
- [29:33]
A
Great reminders all around. All right, guys, well, I think that wraps up another fantastic episode of the fellow on call. Until next time. We'll see you all later.
- [29:40]
B
See you later.