Tag Archive for: Yescarta

How Can I Ensure My CLL Doesn’t Progress to Richter’s Transformation?

How Can I Ensure My CLL Doesn’t Progress to Richter’s Transformation? from Patient Empowerment Network on Vimeo.

What do chronic lymphocytic leukemia (CLL) patients need to know about disease progression? Expert Dr. Ryan Jacobs explains CLL progression, Richter’s transformation, and treatment updates and emerging research on Richter’s. 

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Lisa Hatfield:

And then this patient is asking a pretty specific question, “Cancer patients are always worried about recurrence or worse, a second cancer. How can I be sure that my CLL doesn’t progress to something called Richter’s transformation?” So maybe if you can explain what that is, talk about that a little bit, the Richter transformation?

Dr. Ryan Jacobs:

Yeah. It’s a really aggressive transformation of the CLL into a high-grade B-cell lymphoma. It’s generally a situation where the cancer cell was a CLL cell and then becomes more aggressive and kind of becomes the dominant cancer, because it’s a lot more aggressive than the CLL. The CLL is still there, but then now you’ve got this aggressive lymphoma on top of it.

We are still treating it like we do other aggressive lymphomas in general. We are trying to find better ways to treat it, because these patients do not have good outcomes with standard lymphoma treatments. I’ve been having success recently for my patients that relapse after chemo, and the large majority of patients will relapse after chemo, but I’ve been having some recent success using CAR T in those patients, and also now have a, I was thankfully getting it sort of off-label approval to do that, but now I actually have a clinical trial investigating axicabtagene ciloleucel (Yescarta) in those patients.

So that’s one area where we’re looking, but we like to manage first-line treatment better. There’s going to be a couple of…I was looking at the big cancer meeting, ASCO is coming up, and that’s usually a meeting that’s much more focused on solid tumors, but there usually are a handful of lymphoma presentations. There wasn’t really much to get excited about, I would say, in terms of big presentations from specifically treatment of CLL, but there were a couple of oral presentations, big presentations for Richter. So that’s really great to see. It’s a very hard disease to do clinical trials in, because generally the patients present so aggressively that you just have to emergently start treatment, and putting patients on clinical trials takes a little extra time in most circumstances, so it’s so hard. But there’s, looks at more data with CAR T and Richter, so we’ll get some more information there, with specifically the Liso-Cel product, which is a different CAR T. And then there’s also looking at doing some immune-based therapies to treat relapsed Richter’s as well. That data hasn’t been released yet, so I’ll be interested when they put that data up preceding the presentations.

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DLBCL Treatment Approaches for Newly Diagnosed and Relapsed/Refractory Patients

DLBCL Treatment Approaches for Newly Diagnosed and Relapsed/Refractory Patients from Patient Empowerment Network on Vimeo.

What are current diffuse large B-cell lymphoma (DLBCL) treatment approaches for newly diagnosed and relapsed/refractory patients? Expert Dr. Amitkumar Mehta outlines treatment options, explains how treatments have evolved, and discusses patient monitoring following treatment completion.

Dr. Amitkumar Mehta is Director of the Lymphoma Program and CAR T Program and Medical Director of the Clinical Trials Office at O’Neal Comprehensive Cancer Center at UAB. Learn more about Dr. Mehta.

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What treatment options are available for DLBCL patients?

Dr. Mehta:

So, it’s a very loaded question because, you know, front-line and relapse and field has evolved immensely over a period of years. But I’ll tell you that in a new diagnosis of DLBCL, still R-CHOP or R-EPOCH-based treatments are standard of care. We have – as a medical community, we have tried multiple times to improve upon the foundation of R-CHOP or R-EPOCH. But we have failed, unfortunately, that R-CHOP is still the best treatment.

There are multiple clinical trials, which are building on R-CHOP adding novel agents and see whether it gets better or not. So, therefore, when we discuss, we discuss always to ask about whether there is any clinical trial option. If the DLBCL comes back, which happens in about 30 to 40 percent of cases, there are so many treatment options.

There are novel options including bone marrow transplant. The CAR-T treatment, tafasitamab (Monjuvi), different CD19-directed therapies, or loncastuximab (Zynlonta) CD19-directed antibody drug conjugate. There are so many – polatuzumab (Polivy) – options available. Therefore, it is important to have a discussion with your provider that “Okay. Well, if it has come back, of course, it is disappointing. But what are my options, clinical trial options, novel therapeutic options,” so that we can work as a team with betterment and hoping to cure even if it has come back, a large cell lymphoma.

So, there are so many treatment options out there. I did not touch upon the clinical trial. There are so many clinical trials going on within amazing agents, which are very effective in DLBCL.


How are DLBCL patients monitored after treatment is completed?

Dr. Mehta:

Very importantly, if you go in remission and after the initial treatment or in a relapse setting, we have to keep an eye. And, of course, we want to detect if it comes earlier so that we can start the treatment earlier. Typically, in the beginning, in the initial two years, the follow-up could be closer, every four to six months we get together.

We have labs done. Sometimes we do scans, making sure that a lymphoma – there is no evidence of it coming back. So, the initial two to three years the follow could be closer. And then, as we space out, the follow spaces out further. And then, after you have a five-year mark where the lymphoma has not come back, the chance of it coming back goes further down. So, then I start follow-up annually on those patients. Yeah.

An Overview of Current DLBCL Treatment Approaches

An Overview of Current DLBCL Treatment Approaches from Patient Empowerment Network on Vimeo.

What do diffuse large B-cell lymphoma (DLBCL) patients need to know about current treatment approaches? Expert Dr. Loretta Nastoupil provides an overview and gives an update about ongoing research comparing two treatment regimens.

Dr. Loretta Nastoupil is Director of the Lymphoma Outcomes Database in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil, here.

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Dr. Nastoupil, now that we’ve discussed factors that go into the treatment choices, can you walk us through the currently available DLBCL treatment approaches and who they might be right for?

Dr. Nastoupil:

Absolutely. So, again, this is changing, and that’s good news. So, up until recently, R-CHOP or rituximab in combination with CHOP, which is an acronym for four different drugs, cyclophosphamide, doxorubicin, vincristine, and prednisone, has been our standard.

Again, what would potentially challenge that is the POLARIX study where we exchange vincristine for polatuzumab. We don’t know the results of that study yet. All we know is that it met its primary endpoint, meaning it met what it set out to do in terms of improving upon some of the outcomes achieved with R-CHOP.

We need to see the details to know if that means now every newly diagnosed diffuse large B-cell lymphoma patient will be offered the polatuzumab in combination with R-CHP study or whether or not there will still be some patients appropriate for R-CHOP.

But that is generally our first approach. Whether you get six cycles or a shortened course plus/minus radiation depends on your state. Once patients have completed therapy, generally, then we pursue what’s called surveillance.

So, we’re monitoring for any signs that the lymphoma has recurred or has not gone away. That’s a controversial topic in terms of how to conduct surveillance and one that I suspect will change over time. But for most patients, if the lymphoma is going to recur, it generally recurs within the first two years.

So, assessing patients either in the form of a CT scan, a PET CT, or a physical exam with labs every four to six months for the first two years is what most practices will pursue. I’m not saying that there is no chance that you would relapse beyond two years. It’s just that the majority of patients, at least 90 percent, if the lymphoma comes back, it usually does so within two years.

And the relapses that occur beyond two years are less predictable. They could happen at three years. They could happen at 10 years, as it’s hard to know how to do surveillance beyond two years.

If the lymphoma recurs, the first thing we need to do is biopsy it because there are many things that can mimic lymphoma on a scan – infection, inflammation, other tumor types. So, if there is ever a question about whether or not the lymphoma has recurred, I generally advise for all patients they undergo a biopsy to ensure that we know what we’re treating.

Depending on when the lymphoma recurs, if it happens within 12 months, this is another area that we are shifting our practice. In the past, for all patients who had relapsed large cell lymphoma, we would pursue what we call salvage or second-line chemotherapy. So, we mix up the chemo. We keep, generally, the rituximab, but we alter the chemotherapy agents. We wouldn’t give CHOP again.

And then we give a shortened course where we give two to three cycles. We repeat the scan. And for patients who’ve achieved what we call chemo-sensitive disease – so, that’s generally a complete response on scan – we would then move forward with high-dose therapy and an autologous stem cell transplant. So, essentially giving different but more intense chemo and rescuing patients from that maneuver with their own stem cells that will go back to the bone marrow and start making white blood cells, red cells, and platelets again.

What has shifted in the last six months is we now know that CAR T-cell therapy is superior to that approach, at least with two CAR Ts for patients whose lymphoma came back within 12 months. Again, we’re eagerly awaiting the full results of those randomized studies. But three trials were conducted. Two of the three suggest CAR T is better than second chemo and transplant for those patients who relapse within 12 months.

So, currently, we think that you’ll have a CHOP-like therapy with plus rituximab frontline. If you progress within 12 months, you potentially would be a candidate for CAR T-cell therapy. If the CAR T-cell therapy fails, which is true for about half of patients. Or if you’re deemed to not be a candidate for CAR T, we have several other new options that didn’t exist a year ago, including targeted or non-chemotherapy options.

So, there are at least four options in that setting now that are therapies that target the lymphoma cells, either by targeting CD19, which is another surface marker, augmenting that either with an antibody drug conjugate, such as loncastuximab tesirine (Lonca), or with an immune therapy, such as lenalidomide (Revlimid) and tafasitamab. Polatuzumab (Polivy) is available in that third line or later space combined with bendamustine (Treanda) and rituximab (Rituxan). There’s an oral agent called Selinexor (Xpovio).

So, a lot of that is not to burden patients with information but to let them know they’ve got lots of options. And many of these can be sequenced. So, if we can’t achieve cure with R-CHOP and/or CAR T, there are still very good outcomes in that third line or later space.