Early Relapsed DLBCL Counseling Includes CAR T and Alternative Therapy

Patients with diffuse large B-cell lymphoma (DLBCL) that is primary refractory or relapses within 12 months have the option of 2 different chimeric antigen receptor (CAR) T-cell therapies. In a virtual Case-Based Roundtable meeting for oncologists in Michigan, participants discussed the need to refer these patients to a tertiary care center for evaluation in most cases. Matthew Lunning, DO, Assistant Vice Chancellor of Clinical Research and Associate Vice Chair of Research of the Department of Internal Medicine at the University of Nebraska Medical Center, who moderated the event, also asked participants in which cases they would treat these patients in their clinic with other therapies including salvage chemotherapy and hematopoietic cell transplant.

Register today to join a Case-Based Roundtable near you.

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

• A 67-year-old man presented with fatigue, back pain, and lymphadenopathy.
• Medical history: Hypertension is well controlled with medication​.
• Physical exam: left posterior cervical, 1.5-cm node; right anterior cervical node, 2.5 cm; left supraclavicular node, 2.0 cm​
• PET-CT scan: multiple enlarged mesenteric and retroperitoneal nodes, with the largest being 5.3 × 3.1 cm
• Bone marrow biopsy: negative​
• Lymph node biopsy: confirmed DLBCL, non-germinal center B-cell, double-expressor lymphoma
  • Immunohistochemistry (IHC) positive for: CD20, BCL6, BCL2 (50% of cells), MYC (> 40% of cells), Ki67 (85%), MUM1​
  • IHC negative for: CD10​
• Fluorescence in situ hybridization: negative for translocations involving MYC, BCL2, BCL6​
• Laboratory results: lactate dehydrogenase elevated; complete blood count normal​
• Stage III; non-germinal center
• International prognostic indicator (IPI): high-intermediate risk
• ECOG performance score: 1 ​
• Rituximab (Rituxan), cyclophosphamide, hydroxydaunomycin, vincristine sulfate (Oncovin), and prednisone were initiated for 6 cycles.
• Back pain resolved​
• Posttreatment PET scan demonstrated a complete response (CR) with a Deauville score of 2; patient was observed​ after.

Eight months after completion of therapy​

• The patient complained of fever, night sweats, and back pain. ​
• A palpable lymph node in the left groin was discovered on physical examination​.
• PET and CT scan: new left inguinal lymph node, increase in size of residual nodes, as well as multiple metabolically active lesions in lymph nodes of the retroperitoneum, abdomen, and pelvis​
• Biopsy confirmed DLBCL, but next-generation sequencing was not performed.
• The patient was referred to the nearest transplant and cellular therapy center for evaluation.

DISCUSSION QUESTIONS

• What is the prognosis for a patient like this?​
• What therapeutic options would you consider for this patient?​
• What does prescreening for CAR T referral entail?

Matthew Lunning, DO: For this patient with relapse 8 months after they achieve a CR to R-CHOP, what are you talking to the patient about what their prognosis may be?

Carole Miller, MD: Their prognosis is much worse than if they relapse after 2 years, but we still have therapies that can get them back into remission with potential cures. It depends how sick they are when they relapse and whether they are candidates for more aggressive therapies. I talk to them about how this is high risk. Given that we have potentially good second-line therapies, I don't make it all doom and gloom, but…it's the primary refractory [cases] that are most worrisome. They can potentially be treated with CAR T cells; in Baltimore, we still do allogeneic transplants for primary refractory, at least at Johns Hopkins. We tend to treat them aggressively.

Lunning: Are you referring these patients with primary refractory disease to a tertiary care center to have the discussion of CAR T cell vs second-line therapy and consolidated allogeneic transplant?

Carole Miller, MD: Yes, I always refer them. Sometimes they ask us to do the treatment before, [and] we will do the treatment. I refer them for evaluation if they're clinically appropriate and healthy enough to get it. With each CAR T-cell regimen, you want to treat them with the salvage regimen that [the specialist] wants…so I like them to be seen as soon as possible.

Lunning: Dr Alhyari, are you following the Center for International Blood and Marrow Transplant Research data that say transplant may be OK if you can get them into a CR? Are you thinking this is a relapse at 8 months, and it fits the bill for ZUMA-7 [NCT03391466] and TRANSFORM [NCT03575351], so you're referring them for CAR T cells?

Mohammad Alhyari, MD: We would typically proceed with CAR T-cell therapy at this point. He's symptomatic. Most patients would be symptomatic and would require bridging therapy.

Lunning: Dr Stone, I know that you probably do some CAR T cell intervention or evaluating patients. What are you doing in your practice for prescreening for CAR T cells?

Steve Stone, MD: We don't tend to refer preemptively, but we would be sending this patient immediately with this relapse. We probably would have treated this patient with pola-R-CHP [polatuzumab vedotin (Polivy), rituximab, cyclophosphamide, hydroxydaunomycin, and prednisone] because of the ABC subtype, the double expressor, and high IPI. I don't know if that would have changed their long-term outcome. But one thing we would do is biopsy, making sure that there's CD19 expression, assess their functional capacity, their frailty, see what's left of their renal function, all of these things.

Lunning: [It’s important to] get them prepared for where you're sending them in these situations where every day does matter and getting them to their CAR T cell, lining it up so that when they get referred, they're not repeating tests, and they can just move forward and you’re trying to get them to apheresis as quickly as possible.

I think one of the interesting thing that we're seeing in evolution is we have higher IPI score patients as we start to see the longer term 3-year data from ZUMA-12 [NCT03761056], as well as now ZUMA-23 [NCT05605899], which is that high-risk IPI 4 or 5 patient population being randomly assigned to either axicabtagene ciloleucel [axi-cel; Yescarta] or continuation of their frontline induction therapy. We are trying to enrich for that high-risk patient population moving into earlier CAR T cell.

DISCUSSION QUESTION

• In which instances would you consider continuing to manage the patient vs referring for CAR-T cell therapy in the second line?​

Tareq Al Baghdadi: Pertinent to this question is a relatively recent data set.¹ It's retrospective, showing that patient who relapsed within a year but got salvage, and responded to salvage and then got autologous transplant, did just as well as CAR T. This is not comparing 2 strategies of treatment. You're taking a small population of patients who responded to salvage, then you can do autologous transplant for those patients. These are retrospective data. Many of those patients require salvage therapy. They can't wait to have the cells collected and then wait for processing, so many times I do give salvage therapy. Sometimes you're faced with patients who either don't want to go on CAR T despite initially having the discussion or then going to the meeting and for some reason favor autologous transplant.

Borys Hrinczenko, MD: I probably would have them go for a consultation and get the opinion of the hematologic malignancy physicians. The problem also is the question of travel; it's at least an hour or so away and there is a lot of construction on the roads here in Michigan that adds another half hour to an hour to any kind of travel. I would also look at their clinical state, their age, and performance status, and all those other issues.

Lunning: Dr Pounders, I know that you said that you have both CAR T cell and bispecifics available to you. Are there situations where you're getting second-line glofitamab [Columvi] plus gemcitabine/oxaliplatin [GemOx] in lieu of CAR T-cell here? And how are you selecting between axi-cel and lisocabtagene maraleucel [liso-cel; Breyanzi], or do you only have 1 available in your practice?

Zachary Pounders, DO: I don't make the decision about the CAR T product. We have transplanters who work directly with us. I think axi-cel is what we use. Typically, I'm going directly to a bispecific in a patient who has been seen by the transplanter or is unlikely to make it to transplant. In West Michigan, we have patients as far north as 2.5 to 3 hours away from our hospital, and about the same distance south. So there's a practical aspect to it, managing patients who live in very rural [areas] or have very minimal resources, who don't necessarily have support to go to the transplant center, or don't have family support and are unable to have the aftercare necessary to go through with CAR T or autologous transplant, and in those patients, I would fall back on a more conventional second-line treatment.

Lunning: Dr Alhyari, do you have liso-cel and axi-cel?

Mohammad Alhyari, MD: I believe I've seen both be offered. I don't typically go to a bispecific, unless patients…did not want to get CAR T and were younger, fit patients who decided against it. We have used glofitamab/GemOx if we are in doubt if a patient will be offered CAR T or not.

Rana Bilbeisi, MD: A couple of patients in our practice had difficulties with transportation. We're only half an hour from the main center, so it's not bad. It's just a lack of patient resources, no family around them, and it does become an issue. It has delayed people getting evaluated.

Register today to join a Case-Based Roundtable near you.

DISCLOSURES: Lunning previously reported receiving honoraria and/or has served in a consultancy or advisory role for AbbVie, Acrotech, ADC Therapeutics, AstraZeneca, Astellas, Bristol Myers Squibb, Caribou, CRISPR, Daiichi Sankyo, EUSA, Fate Therapeutics, Genentech, GenMab, InstilBio, Ipsen, Janssen, Kite, Loxo, Miltenyi, MorphoSys, Novartis, Nurix, Pharmacyclics, Regeneron, Sanofi, Seagen, Takeda, and TG Therapeutics; and has received research funding from Bristol Myers Squibb, Curis, FATE Therapeutics, and Sana Therapeutics. There were no other known relevant disclosures.

REFERENCE:

1. Shadman M, Pasquini M, Ahn KW, et al. Autologous transplant vs chimeric antigen receptor T-cell therapy for relapsed DLBCL in partial remission. Blood. 2022;139(9):1330-1339. doi:10.1182/blood.2021013289