 We’re going to start with a case of a 77-year-old woman who presents with anorexia, fatigue, and shortness of breath. Her past medical history is notable for having diabetes that is medically controlled. On physical examination, she has palpable inguinal lymphadenopathy and splenomegaly, and we assess her ECOG performance status to be 1. Her laboratory evaluation is notable for anemia, with a hemoglobin of 9.8 [g/dL], and she has an elevated LDH [lactate dehydrogenase]. By pulmonary function test, she has an FEV1 [forced expiratory volume in the first second of expiration] of 45%. Hepatitis B, C, and HIV tests are all negative.

You proceed with a core needle biopsy of the inguinal lymph node. That demonstrates a CD20-positive diffuse large B-cell lymphoma [DLBCL], nongerminal center B-cell [GCB] subtype. You get a FISH [fluorescence in situ hybridization] panel back that demonstrates a translocation between chromosomes 14 and 18, consistent with a 

 rearrangement, but she does not have a rearrangement of 

A staging PET [positron emission tomography]/CT scan demonstrates FDG [fluorodeoxyglucose]-avid inguinal lymphadenopathy measuring up to 3.3 cm, FDG-avid splenomegaly, and a small—1 cm—suspicious lesion in the lung. A bone marrow examination confirms involvement with diffuse large B-cell lymphoma.

In conclusion, we have a patient with stage IV diffuse large B-cell lymphoma, nongerminal center B-cell subtype. It is not a double hit. You assess her IPI [International Prognostic Index] score to be high risk, and her CNS [central nervous system] relapse score to be intermediate risk, meaning that she does not require prophylactic intrathecal or high-dose methotrexate therapy.

She’s 77 years old. You treat her with 6 cycles of R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] chemotherapy. At the end of treatment, a PET/CT scan demonstrates a Deauville 2 score complete remission.

One year later, while she’s in surveillance, she presents with new onset of diffuse lymphadenopathy involving cervical, axillary, mediastinal, and abdominal regions. A core needle biopsy of an axillary node confirms a relapse of her original DLBCL, non-GCB subtype. Based on her age, 78 years at this point, and performance status, you consider her to be transplant ineligible. You elect to initiate therapy with tafasitamab plus lenalidomide.

Case Overview: 77-Year-Old Woman With DLBCL

 When assessing risk in a patient with newly diagnosed diffuse large B-cell lymphoma [DLBCL] we still use the old-fashioned International Prognostic Index [IPI] or the Revised International Prognostic Index [R-IPI]. This consists of 5 factors, abbreviated as APLES, which is age, performance status, LDH [lactate dehydrogenase], extranodal sites, and stage. I think almost all oncologists are familiar with this clinical score, and it’s still used in clinical practice today.

Patients with poor-risk disease, as this patient had, have an estimated 4-year progression-free survival of about 50%. Besides the IPI score, another thing that I think is important to look at is cell of origin. In clinical practice, we estimate the cell of origin using immunohistochemistry [IHC]. Initially, the cell of origin was described by gene expression profiling and classified as germinal center B [GCB], activated B-cell subtype, primary mediastinal subtypes. When using IHC, we estimate that as being either germinal center B or nongerminal center B. So that’s important to look at. We know that the nongerminal center B subtype, or the activated B-cell subtype, has a less favorable prognosis than the germinal center B subtype, for the most part.

Another important factor to think about when you have a newly diagnosed patient is whether the patient has so-called double hit or triple hit DLBCL, meaning there’s a combination of rearrangements in the 

 genes, or both. Having 2 rearrangements is called double hit, and having 3 rearrangements is called a triple hit. Those patients have a particularly unfavorable prognosis and may be more appropriately treated with more aggressive chemotherapy regimens than R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone].

The final thing I’d point out is that I think it is important to remember to try to calculate the CNS [central nervous system] relapse risk in newly diagnosed DLBCL patients. In clinical practice, that might get forgotten. The NCCN [National Comprehensive Cancer Network] has listed a formula on its website. Basically, you get a point for various things, some of which are already in the IPI, and there are additional points for kidney or adrenal involvement. There are certain patients who may automatically, by their diagnosis, benefit from CNS prophylaxis. So it is important for practitioners to remember to calculate that CNS relapse risk score and, for high-risk patients, consider some type of CNS prophylaxis along with treatment.

Approaching DLBCL: Risk Assessment and Prognosis

 In my hospital, the timing on FISH [fluorescence in situ hybridization], from the biopsy to when I get the results back, tends to be between 1 and 2 weeks. It’s usually not more than that. My hospital is sending FISH testing out to central laboratories around the country, so there is shipping involved.

Most of the time, when a patient is newly diagnosed, it still takes some time to get them coordinated for treatment. They have to undergo a PET [positron emission tomography]/CT scan. They have to get labs drawn. They have to learn about the disease. They have to learn about adverse effects. All of that takes enough time for which, in my practice, usually the FISH result is back before I need to initiate therapy.

There are occasions when patients need to be treated quickly because they’re so sick. We have to start them on treatment in the hospital before we have FISH results back. However, I would say that’s the minority. In the case where someone is in that situation and gets a cycle of R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone], and then, low and behold, the FISH comes back showing a double hit and you want to use a more aggressive regimen, I don’t lose any sleep if they got 1 cycle of R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone]. I can use a more aggressive regimen for all of their subsequent treatments. I don’t think it’s a big deal if the FISH results take a little bit longer, but most the time I have results back, even in a community practice like mine.

The question as to whether I do additional molecular testing in diffuse large B-cell lymphoma besides the FISH, my answer is generally not. You ask, what kind of molecular testing are we talking about? One is gene expression profiling, and generally that is not performed outside of clinical trials. To date, distinguishing the gene expression profile has not changed the treatment regimen that we use. We use the same, R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone], for germinal center B-cell subtype that we use for nongerminal center B subtype. Although attempts have been made to change the treatment, particularly for the nongerminal center B, or activated B-cell subtype, none of those trials have turned out positive so far. So that doesn’t really affect clinical practice.

The other rationale that one might think about for using the next-generation sequencing panel would be to calculate the m7-FLIPI [Follicular Lymphoma International Prognostic Index] score. M7-FLIPI refers to 7 gene mutations that can be incorporated into a calculation to further refine a prognosis in follicular lymphoma. This is not really used in large cell lymphoma, but more so for follicular lymphoma. But again, it’s not a perfect test. It doesn’t have a lot of impact in clinical practice, so I’m not generally doing molecular profiling in my large cell lymphoma patients, or in my follicular lymphoma patients either.

DLBCL: Cytogenetic Testing and Treatment Initiation

 This patient has a pretty straightforward diffuse large B-cell lymphoma. The standard practice remains using R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] chemotherapy as treatment. In a 77-year-old, as this patient was at presentation, certainly if her performance status was impaired or if she had comorbidities and one felt R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] might not be safe, then the treating physician needs to think about alternatives. There is no standard in that situation, although many physicians will reduce the doses of the CHOP [cyclophosphamide, doxorubicin, vincristine and prednisolone] in the form of R-miniCHOP therapy. Or if patients have inadequate cardiac function, you need to modify the CHOP [cyclophosphamide, doxorubicin, vincristine and prednisolone] and use something like etoposide in place of the doxorubicin. Various other regimens can be used in folks with impaired cardiac function. But for a straightforward large cell lymphoma case like this, R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] remains the standard of care.

For the double hit lymphomas, it’s a little less clear what exactly is the best regimen. It’s not 100% clear from phase 3 trials at least, that more aggressive regimens are better than R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone]. The data supporting these aggressive regimens in double hit lymphomas come from phase 2 trials where results appear to be better than they are with R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone]. Dose adjusted R-EPOCH [rituximab with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin] is a commonly used regimen in community practices for patients with double hit lymphoma.

Again, the default is going to be R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] for most patients. If patients have comorbidities, that will impact the choice of first-line treatment. Knowing if the patient has a double or triple hit lymphoma will impact the choice of therapy. Those are the primary factors that impact the choice of treatment.

As for the success rates with R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] chemotherapy, most studies will indicate an overall response rate somewhere between 75% and 90%, a complete remission rate between 55% and 70%, and a 3-year progression-free survival on the order of 65% to 70%. We generally tell patients that long-term cure rates after R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] are in the ballpark of 60%.

Frontline Treatment Approaches in DLBCL

 One important point that I think can get overlooked not infrequently is that not everyone who has a positive PET [positron emission tomography] scan at the end of treatment actually has persistent disease. It’s really important, if a PET scan is positive and the treating physician is concerned about that, to repeat a biopsy to make sure that we are in fact dealing with persistent disease, because that’s not always the case. Some of the best data to support that are from a study called REMARC, where patients were treated with R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] and then randomly assigned to maintenance lenalidomide or observation.

Of the patients on that study who were in a partial remission at the end of induction, meaning they were thought to have residual disease, 29% converted to complete remission with no additional therapy on the observation-alone arm. A number of PET scans that were positive simply became negative with time. Clearly, those patients had abnormal PETs—they were not in a complete remission—but didn’t necessarily ever relapse. Again, I think that proves the point that a lot of these positive PETs do not necessarily reflect persistent disease. So it’s important to do a biopsy if a PET is positive and you’re concerned about this being primary refractory disease. Overall, I think about one-third of patients with large cell lymphoma will eventually relapse after R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] therapy. That progression-free survival of about 60% to 65% means that about one-third of patients are relapsing.

I think you asked, what are the treatment options for patients with relapsed disease? It’s an area right now that’s changing rapidly. We’ve basically had 3 new approvals within the last year, so it’s an exciting time and there’s a lot to talk about here. For most patients, the first thing we do when we see a patient with relapsed large cell lymphoma is ask ourselves whether they’re eligible for autologous stem cell transplant. We think that has the highest likelihood of cure for patients with relapsed large cell lymphoma. If a patient is eligible for a transplant, we will offer them salvage chemotherapy with a regimen such as ICE [ifosfamide, carboplatin, and etoposide] with or without rituximab. Or we could offer DHAP [dexamethasone, high-dose cytarabine, and cisplatin] with or without rituximab. And then if they have chemotherapy-sensitive disease and achieve at least a partial response, we can follow that chemotherapy with high-dose therapy and autologous stem cell transplant. That’s probably the preferred modality for many patients.

There are patients who relapse, who are immediately known to be ineligible for transplant either by age or comorbidities or performance status. Those patients do not have, of course, the option of doing a stem cell transplant. Those patients generally can be treated either with conventional chemotherapy—an example of a regimen might be rituximab plus gemcitabine with or without oxaliplatin—or, as of last year, we have the combination of polatuzumab vedotin plus bendamustine plus rituximab. Now, I say that, and the study of that combination did treat patients in both the second-line setting and third-line setting and beyond, but the FDA approval and NCCN [National Comprehensive Cancer Network] guidelines are written such that patients who are eligible for that treatment regimen should have received at least 2 prior therapies. In both of those cases, it’s listed as a third-line option. However, in my opinion, it can be used as a second-line option for patients known to be transplant ineligible. Again, those patients were included on the study.

We now have a new option for transplant-ineligible patients in the second line, which is the combination of tafasitamab plus lenalidomide. We’ll come to that regimen and will discuss that a little bit more in a minute.

CAR [chimeric antigen receptor] T-cell therapy is the preferred third-line treatment modality right now. For patients who are not eligible for CAR T-cell therapy, they would have the option of a salvage chemotherapy regimen. Again, rituximab plus gemcitabine with or without oxaliplatin is 1 example. Another option is polatuzumab/bendamustine/rituximab. In the third-line setting, that regimen is approved and NCCN recommended. We have tafasitamab plus lenalidomide, again FDA approved and NCCN recommended. We also now have the new drug selinexor approved and available in that space. So, we have many options for third-line therapy and beyond.

Current Treatment Approaches for R/R DLBCL

 L-MIND is a study that led to the FDA approval of the combination of tafasitamab plus lenalidomide. What is tafasitamab? Tafasitamab is a humanized anti-CD19 monoclonal antibody. It has what’s called an engineered Fc portion of the antibody. There are 2 amino acid substitutions in the Fc portion that increase the binding affinity of that Fc portion to the Fc gamma receptors on effector cells like NK [natural killer] cells and macrophages. Tafasitamab leads to NK cell-mediated, antibody-dependent cellular cytotoxicity, or ADCC. It also leads to macrophage-mediated antibody-dependent cellular phagocytosis, or ADCP, and it can cause direct cell death of lymphoma cells.

Why combine tafasitamab with lenalidomide? As single agents, tafasitamab and lenalidomide don’t have great responses. There are responses, but the thought was they could provide better responses. Lenalidomide stimulates proliferation and activation of those NK cells that could mediate that ADCC. We know that in vitro, the combination of lenalidomide plus tafasitamab successfully increased NK cell-mediated ADCC compared with tafasitamab alone. That was the rationale to combine these 2 drugs, and that’s what led to the design of the L-MIND trial.

L-MIND was a phase 2 trial. Eligible patients had relapsed/refractory diffuse large B-cell lymphoma [DLBCL] and had been treated with 1 to 3 prior regimens. Patients with primary refractory DLBCL were excluded. Eighty-one patients were enrolled on the trial. All patients received the combination of tafasitamab plus lenalidomide. Tafasitamab is given intravenously on a weekly schedule for the first 3 months and then every other week thereafter. The dosing of lenalidomide was 25 mg by mouth daily on days 1 through 21 of a 28-day cycle. The combination was continued for a year, after which tafasitamab was continued alone. So, lenalidomide was stopped at 1 year.

The primary end point of the study was overall response rate. The patients enrolled had a median age of 72 years. They had a median number of prior therapies of 2, and almost half of the patients had received only 1 prior therapy. They weren’t the most heavily pretreated population. Forty-four percent of such patients were refractory to their previous therapy, and 11% of patients had received a prior autologous stem cell transplant.

The efficacy results were reported at a median of 27 months; this was the latest report as of EHA [the European Hematology Association annual meeting]. The overall response rate was 59%, the complete response rate was 41%, the median duration of response was 35 months, the median progression-free survival was 16 months, and the median overall survival was almost 3 years—32 months. Certainly, these are pretty good results for a relapsed/refractory lymphoma population.

In regard to toxicities, the most common hematologic toxicity was neutropenia. They saw grade 3 or 4 neutropenia in 48% of patients, febrile neutropenia in 12% of patients, and grade 3/4 thrombocytopenia occurred in about 17% of patients. Nonhematologic toxicities seen included rash, diarrhea, and fatigue. Serious adverse events occurred in 18% of patients. Infusion reactions were not common. They were reported in only 6% of tafasitamab-treated patients, so probably fewer infusion reactions with tafasitamab than things we’re used to, like rituximab.

Lenalidomide dose intensity was maintained fairly well. Seventy-eight percent of patients were able to stay on at least 20 mg per day, or higher. Dose reductions were required in 43% of patients.

Based on these results and also on the results of a retrospective comparison with lenalidomide alone called Re-MIND, the FDA saw fit to approve the combination of tafasitamab plus lenalidomide very recently.

The primary and secondary end point outcomes are fascinating. We saw an overall response rate of about 60%, and a complete response rate of about 40%. In the CAR [chimeric antigen receptor] T-cell results, we see complete remission rates of 50% to 70%. These results are fairly impressive for a salvage chemotherapy-type treatment. This isn’t conventional chemotherapy. I think people are pretty impressed by the data here. That said, it’s risky to compare across trials. You shouldn’t be doing it, because there are different patient populations in some of these different relapsed lymphoma trials. It’s possible that the drugs are just darn effective. They clearly are, but as I mentioned before, it wasn’t the most heavily pretreated population—with a median of 2 prior therapies but 49% of patients having received only 1 prior therapy. Again, there are other trials out there that have more heavily pretreated patients.

The other factor here is that they excluded primary refractory disease, which we know has a less favorable outcome and less chemotherapy sensitivity compared with patients who relapse a year later, like the patient in our case. While they excluded primary refractory disease, about 18% of the patients on the trial did have primary refractory disease that had relapsed between 3 and 6 months. But again, that factor might have impacted the response rates that we’re seeing. But, clearly it’s still an effective treatment that’s nice to have available for patients.

In terms of the toxicities, there’s a comparison between the toxicities that occurred on the combination part of therapy and the toxicities that occurred on the tafasitamab-alone arm after 1 year of therapy. You can see that the toxicities go down significantly for the patients who are on tafasitamab alone. A lot of the toxicities from this combination are coming from the lenalidomide. We think most of the neutropenia, certainly the rash, some of the diarrhea, may be coming from the lenalidomide. For doctors who are accustomed to treating patients with lenalidomide, as most of us are, we’re pretty good at it and we feel that lenalidomide has manageable toxicities. This is a relatively well-tolerated regimen that any oncologist should be comfortable giving once you get the hang of it.

Implications for Treating R/R DLBCL With the L-MIND Regimen

 I think Re-MIND is a really interesting trial. A lot of people may not know about it just yet. It was presented on at ASH [the American Society of Hematology annual meeting] in 2019 and more recently at some of the summer meetings. This was a retrospective study. The scenario here was that we have a combination of tafasitamab plus lenalidomide that appears to be effective, but the question was, what are the individual contributions of the different drugs? We don’t really have great data on the outcomes with lenalidomide alone. So how much of the benefit here is from the lenalidomide, how much is from the tafasitamab, and how much of it is from the combination?

There are a couple of ways to answer that question. One is to do a randomized trial where you compare the individual arms and the combination arm. Or, you can do what they did instead, which was really innovative. They went back and did a retrospective study. They found more than 400 patients who had been treated with lenalidomide alone, as monotherapy, for relapsed large cell lymphoma. This is more commonly done in Europe, so most of the patients on this trial came from Europe. They did a matched comparison between the L-MIND patients and the patients in this retrospective cohort. So of those 400 patients, they matched them for these covariates, including age, performance status, white blood cell count, and a whole bunch of other factors, to get as close of a matching between the 2 groups as possible. They came up with 70-something patients in each group who were sort of head-to-head comparisons. Of course, they weren’t identical, but when you look at the data they were pretty darn close to being well matched. Then they compared the outcomes in those, I think, 76 patients in each group.

When you look at the overall response rate in the L-MIND cohort, again it was 67%, whereas in the lenalidomide-alone cohort, it was 34%. So, basically almost double the response rate with the combination regimen. The complete remission rate was 40% with the combination regimen versus 13% with single-agent lenalidomide. And the overall survival was significantly improved with the combination regimen compared with single-agent lenalidomide.

As best as we can tell using this innovative design, it would appear that the combination significantly improves outcomes compared with lenalidomide alone. This indicates that the addition of tafasitamab is clearly providing a benefit above and beyond what one would get with lenalidomide alone. I’m sure it was not an easy study to conduct, but they were able to do that without having to conduct a randomized phase 2 or randomized phase 3 trial, and saved a lot of time and money. They were able to make this treatment available to patients more quickly. It’s a neat design, and I’d encourage folks to take a look at the study.

R/R DLBCL: Observations From the Re-MIND Study

 In regard to this particular patient case example, this was an elderly patient who had relapsed 1 year after completing R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone] chemotherapy. The options, in theory, would have included stem cell transplant. Right now, CAR [chimeric antigen receptor] T-cell therapy is only approved as a third-line treatment.

Certainly, there are other chemotherapy regimens that could have been chosen here. This patient would have fit into the L-MIND study criteria, having had relapsed disease and because her physician did not feel that she was transplant eligible based on her age and performance status. I think this was a reasonable choice for this patient. You could use it in the second line, or you could use it as third-line therapy or beyond.

One of the questions about this drug is whether it should be used before CAR T-cell therapy. Why? Well, the drug targets CD19. The theoretical concern is that maybe the targeting of CD19 will remove that protein from the cell, and thereby make the CAR T-cell therapy, which is also targeting CD19, ineffective. Of course, you don’t want to do that.

We don’t have a tremendous amount of data on the answer to that question. There are some in vitro data that were presented at ASH [the American Society of Hematology annual meeting] suggesting that removal of CD19 from the cells probably doesn’t happen. That has been looked at in CLL [chronic lymphocytic leukemia] as well. It does not appear that there’s a big reduction in CD19 on the surface of the cell in CLL after tafasitamab exposure. There have been a few case reports, but not a lot, on successful CAR T-cell therapy after tafasitamab. But again, the data are a bit sparse. That’s one of the theoretical concerns about using tafasitamab in the pre-CAR T-cell therapy space. We don’t yet know the answer, and hope that more data forthcoming will help us understand that impact and relationship better.

R/R DLBCL: Treating With Tafasitamab Plus Lenalidomide

 We have seen tremendous progress in diffuse large B-cell lymphoma in the last 4 or 5 years, with 2 FDA-approved CAR [chimeric antigen receptor] T-cell products, and perhaps a third to come. Polatuzumab vedotin was approved last year in combination with bendamustine and rituximab. This followed the first randomized trial in relapsed large cell lymphoma in recent memory to improve overall survival. That’s a big deal.

We’ve talked a lot about tafasitamab and lenalidomide today. Selinexor is a recently approved oral drug. This is an inhibitor of exportin 1. In the study, there were lower response rates, but in the high 20% range, and responding patients did pretty well. So that’s a new option for patients. There’s a lot going on, we have a lot of new options.

It’s interesting to think about what the right algorithm is right now. As you asked, how do you sequence these new drugs? I don’t think there’s a right answer right now. A lot of it is going to come down to sitting with an individual patient and thinking through the pros, cons, risks, and benefits with them and making the best decision for that patient. Again, if the patient is transplant eligible, the standard remains using a salvage chemotherapy regimen followed by stem cell transplant. If they are transplant ineligible but your goal is to get them to CAR T-cell therapy, then, I haven’t talked to my CAR-T doctors who I refer to about this, but I suspect they’re going to favor something like rituximab, gemcitabine, oxaliplatin, although tafasitamab, lenalidomide may be reasonable. I know there are concerns about bendamustine pre-CAR T-cell collection, but polatuzumab vedotin with bendamustine, rituximab or polatuzumab vedotin with rituximab without bendamustine could be used. So we have a number of different choices there.

If you feel the patient is not headed toward CAR T-cell therapy because of performance status or comorbidities, the field is wide open. Polatuzumab vedotin, bendamustine, rituximab, tafasitamab, lenalidomide, and selinexor are all available in the third-line setting, plus good old-fashioned chemotherapy.

You can sit down with your patients. I think each of these options has pros and cons to think through. With polatuzumab vedotin, a pro is the survival advantage that was seen in a randomized phase 2 trial. Tafasitamab/lenalidomide has a great response rate and a manageable toxicity profile. One disadvantage of tafasitamab/lenalidomide is that we don’t have a chemotherapy comparator arm. We only have the lenalidomide-alone comparator arm. My understanding is that there are some retrospective data going on with an effort to do a chemotherapy comparator study. So, stay tuned on that.

As third-line therapy, CAR T is preferred if your patients can get to it. Not only does CAR T have excellent response rates, but we’re seeing prolonged disease-free survival in about a third of those patients. There are a lot of complex choices to make, and you have to sit down with your patients and go through some of those pros and cons.

In this era of rapidly changing options for diffuse large B-cell lymphoma, doctors certainly need to familiarize themselves with these new drugs and their risks, benefits, and adverse effects. I think having early discussions with transplanters and CAR T-cell therapy providers to whom you refer patients is really important, if you’re not doing those treatments yourselves. It’s important to get them involved in helping map out how to proceed and get this patient to the best available therapy.

Then, it’s important to move quickly, I think it’s conceivable with all these new options that we can turn this disease into a bit more of a chronic disease than it’s been. In these patients who can’t get transplants or who relapse after transplant, relapsed large cell lymphoma has a terrible prognosis. From retrospective studies, we know the median survival is on the order of months. So, it’s essential that we move quickly, get them on some of these effective treatments soon, and again, have those early conversations with your transplant and CAR T doctors you work with to make sure you make as many of these options available to your patients as you possibly can. That’s going to give your patients the best outcome.

A 77-Year-Old Woman with DLBCL