Tafasitamab + Lenalidomide Therapy in Relapsed/Refractory DLBCL

EP: 1.Diagnosis and Frontline Management of Diffuse Large B-Cell Lymphoma

EP: 2.Overview of Relapsed/Refractory DLBCL and Management Strategies

EP: 3.Factors in Selecting Treatment for Relapsed/Refractory DLBCL

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EP: 4.Tafasitamab + Lenalidomide Therapy in Relapsed/Refractory DLBCL

EP: 5.CAR T-Cell Therapy in Relapsed/Refractory DLBCL: Axicabtagene Ciloleucel

EP: 6.CAR T-Cell Therapy in Relapsed/Refractory DLBCL: Lisocabtagene Maraleucel

EP: 7.Real-World Use of CAR T-Cell Therapy in Relapsed/Refractory DLBCL

EP: 8.Factors That Inform Sequencing of Therapy in Relapsed/Refractory DLBCL

EP: 9.Relapsed/Refractory DLBCL: Managing Patients on CAR T-Cell Therapy

EP: 10.What is the Role of Bispecifics in Relapsed/Refractory DLBCL?

EP: 11.Sequencing Novel Therapies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

EP: 12.Bridging Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

EP: 13.Diffuse Large B-Cell Lymphoma: Moving Novel Therapy to the Frontline Setting

EP: 14.Management of Diffuse Large B-Cell Lymphoma: Data From ASCO 2023

EP: 15.Diffuse Large B-Cell Lymphoma: Unmet Needs and Future Directions in Care

Transcript:

Matthew A. Lunning, DO, FACP: Dr Wang, what are your thoughts on the mechanism of action of tafasitamab? Why are they dating or potentially engaged and on their way to get married?

Yucai Wang, MD, PhD: Great question. Tafasitamab is a CD19 monoclonal antibody that’s humanized and has some engineered FC portion, so it binds the CD19 on the cells and the mechanism of cell killing is mainly by antibody-dependent, cellular, subtle toxicity and antibody-dependent cellular phagocytosis, but then you do see a little bit of direct cell killing by apoptosis mechanisms. This works mainly by the immune system. Lenalidomide is a drug that is interesting and has a lot of immune modulatory effect. Maybe when you give the drugs together, lenalidomide can enhance the immune system [so that it] can target the cells that are flagged by the tafasitamab, if you will. In other words, they are synergistic when you give them together.

Matthew A. Lunning, DO, FACP: When you give tafa-len [tafasitamab-lenalidomide] in the relapse/refractory setting—and I think we have some early [clinical trial] data with that first year with tafasitamab and lenalidomide—there can be patients who respond and there can be CR [complete response] achieved and there can be durability. Can you comment about the longer-term follow-up from the clinical trial data with tafasitamab-lenalidomide?

Yucai Wang, MD, PhD: Sure. The trial was initially reported a while ago, and then they had a 3-year update and most recently they had a 5-year follow-up data. The response rate is about the same. You see anywhere from a 40% CR rate and probably a total 60% response rate, with a longer-term follow-up. The exciting thing is you see the durability of the response holds very well. The 5-year data shows the duration of response to the median has now been reached, and overall, the progression-free survival in the entire population is about 1 year. For those who had only 1 prime line of therapy, the median progression-free survival reaches 2 years with the follow-up. The median overall survival, again, is just shy of 3 years for the entire population. For those who only had 1 line of therapy previously, they enjoy overall survival that’s very long at this point and has now been reached by 5 years of follow-up.

Matthew A. Lunning, DO, FACP: It’s great to see those curves people 5 years out continuing to derive benefit and only being on a single-agent antibody every other week. I think that we continue to ask the questions of what those patients who came off or chose to come off the tafasitamab, how those patients are doing. One of the other things that has come out with the tafasitamab-lenalidomide data was the RE-MIND2 [clinical trial] data [NCT04697160]. It’s worth spending some time and talking about how that dataset came about. Can you talk through the several different cohorts from RE-MIND2?

Yucai Wang, MD, PhD: We know L-MIND [NCT02399085] is treating a trial population with tafasitamab plus lenalidomide, and it’s not a randomized control trial. The first-real world study was called RE-MIND, comparing tafa-len in the trial population versus lenalidomide single agent in a real-world population. Of course, you try to match the patient’s disease characteristics that showed a significant improvement compared with lenalidomide single agent; that’s the RE-MIND study [NCT04150328]. Then came along RE-MIND2, which is a larger registry study looking at the relapsed blood cell outcomes in the real-world again. They compared tafa-len outcomes again from the trial to the real-world population. Again, you try to match their disease and patient characteristics as closely as possible. RE-MIND2 enrolled over 3000 patients, a large pool to select the best match to the trial population. The first report of RE-MIND2 showed that the L-MIND regimen compared with the overall dealer’s choice regimen improved overall survival. That has a [hazard] ratio of probably 0.5, meaning a 1 full reduction in risk of dying from the disease. Then if you look at any regimen in the real-world setting, RE-MIND2 compared tafa-len initially with BR [bendamustine plus rituximab] and also with R-GemOx [gemcitabine-oxaliplatin plus rituximab, the older regimens, the hazard ratio is again 0.4 to 0.5. Most recently they also reported some other more modern regimen. They compared tafa-len with polatuzumab-BR. It’s being used recently, so the registry did not have a lot of patients who could match the L-MIND trial, but they have 20 to 30 patients for the pola-BR. And 20 to 30 patients for the R-squared [rituximab-lenalidomide] older regimen. Again, the regimen comparison favored L-MIND. Finally, they compared tafa-len with CAR [chimeric antigen receptor] T-cell therapy, close to 40 patients. They showed that overall survival is comparable in this comparison. We must recognize the limitations of such real-world comparisons, and although you try to match as closely as possible, those are probably unmatched imbalances that we need to consider. Basically, tafa-len works well in the trial population and compared fairly well with historical standard care. We look forward to seeing more, maybe real-world tafa-len data, to see whether that holds against the real world, other practices.

Matthew A. Lunning, DO, FACP: Dr Flinn, you’re in the hot seat here. Dr Wang just gave a nice summary of not only L-MIND but the RE-MIND and the RE-MIND2 [trials] and how that population of patients was compared with the clinical trial population. Tafa-len has been out there. It’s been used in relapse/refractory large-cell lymphoma. How are you using it in your practice, and what’s your overall impression?

Ian W. Flinn, MD, PhD: So there’s another data set that looks at patients in the real-world experience, and the data is not quite as good as it was in the trial. Some people look at that as the cup is half empty, but I think it helps us tailor the way we use the drug. That’s an unfair comparison. The patients were treated with multiple [additional] regimens than were treated in the original clinical trial. There were primary refractory patients that were part of that experience. That to me explains the decrease in the response rates in progression-free survival. It also helps us know when we should be using this. So using it more that was in L-MIND, those patients who weren’t heavily pretreated, they weren’t primary refractory. To me, that’s the ideal setting. If you ask, who is that? To me it’s the person who I’m probably not going to [recommend] the CAR T-cell [therapy]. These are patients who are older patients who perhaps have had 1 prior therapy, maybe 2, [for whom] you can’t use the aggressive regimens. The exciting thing here is that in that patient population, we can probably still duplicate the results that we’re seeing in the clinical trial.

Matthew A. Lunning, DO, FACP: Walk me through your lenalidomide approach. I think the tafasitamab, we’ve seen the [adverse effects] profile in the L-MIND dataset, and kind of in that first year of lenalidomide, you see the lenalidomide effects and you the lenalidomide effects drop off after 12 months. How do you finesse? Lenalidomide to me is a finesser, it’s a nuance, 25 [mg] might not be the right dose for everybody, but there is a right dose of lenalidomide for most patients. How do you get that sense in your practice?

Ian W. Flinn, MD, PhD: That’s right. There’s a little bit of experience in who you’re looking at, who the patient is, walking through what their renal function is, how old they are. Maybe [for] that 83-year-old patient I may not be coming in with full dose right [away], so maybe reducing [it] a little bit, and then going from there and [adjusting the dose] after the first cycle. If the patient unexpectedly did well, then maybe I do go up to [the] full dose. On the other hand, I might be having to [reduce the dose] further based on what their first cycle is.

Matthew A. Lunning, DO, FACP: Are you talking about that initially up front, that…we can modulate the dose of the lenalidomide along the way?

Ian W. Flinn, MD, PhD: Absolutely. I had the same sort of thing when I talk to CLL [chronic lymphocytic leukemia] patients with venetoclax. [The] 400 [mg may not be] the exact right dose ,and we’re going to titrate. You have the same thing here with lenalidomide.

Transcript edited for clarity.