Assessing Treatment Goals in R/R DLBCL

CASE SUMMARY

A 67-year-old man presented with fatigue, back pain, and lymphadenopathy​ and had hypertension well controlled with medication. A physical exam showed a 1.5-cm left posterior cervical node; a 2.5-cm right anterior cervical node; and 2.0-cm left supraclavicular node. A PET-CT scan multiple enlarged mesenteric and retroperitoneal nodes, with the largest measuring 5.3 x 3.1 cm​. A bone marrow biopsy was negative​ and it confirmed non-GCB diffuse large B-cell lymphoma (DLBCL). His immunohistochemistry test was positive for: CD20, BCL-6, BCL-2 (50% of cells), MYC (greater than 30% of cells), Ki67 (85%), MUM1, but negative for CD10. He had normal CBC​ but his LDH elevated​. He was given a diagnosis of stage III, high-intermediate risk disease with a non-germinal center and ECOG performance score of 1.

R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) was initiated for 6 cycles and his back pain resolved, however, 8 months after completion of therapy he complained of returning symptoms. A palpable lymph node in the left groin was discovered on physical examination​. Scans showed a new left inguinal lymph node, increase in size of residual node, as well as multiple metabolically active lesions in lymph nodes of the retroperitoneum, abdomen, and pelvis​. Another biopsy confirmed DLBCL, but next-generation sequencing was not performed.

The patient was referred to nearest transplant and cellular therapy center for evaluation, but ultimately opted not to pursue CAR T-cell therapy. After discussing the treatment options, tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) is initiated.

Discussion Questions

• What are your clinical goals for this patient? ​
• How do you discuss the options during shared decision making with your patients?​
• What are key factors that influence your therapeutic recommendations for a patient with primary refractory DLBCL?

DIANA SUPERFIN, MD: Tafasitamab had less [patients that were treatment] refractory.¹

JOSEPH M. TUSCANO, MD: In the L-MIND study [NCT02399085], they didn’t allow primary refractory patients. But there is some subsequent data and there were some refractory patients on that trial [eventually]. It certainly was not the majority, but that is a good point. Again, is [the patient in this case a] primary refractory patient? Personally, I would call his disease an early relapse with a poor prognosis.

Joseph M. Tuscano, MD

Professor

UC Davis Comprehensive Cancer Center​
Sacramento, CA

What are your goals for the patient? Someone that does not want CAR [chimeric antigen receptor] T-cell therapy and potentially does not want transplant as well. He didn’t say, but he’s not a great candidate for it either.

SUPERFIN: I think [I would want to] get him to durable remission and see if it gives him some time and less toxicity. Who knows, he may agree for CAR T in the third line.

MAHAJAN SHIRISH, MD: Looking at their quality of life and durable responses means a lot with our patient population. Comorbidities in our patient population are high, but we pick and choose.

MING ZHOU, MD: I still try to convince patients to go for curative therapy [and send them to a] tertiary care center. [This patient’s] performance is fine. Maybe he didn’t know that there’s a chance for cure.

GIGI CHEN, MD: I think it depends on his situation. It sounds like he does not want, or he couldn’t go to the tertiary centers for the CAR T [treatment] and does not have a lot of support structure. I think a durable response, convenience of treatment, tolerability and response to the therapy are probably going to be my goals.

CHAINARONG LIMVARAPUSS, MD: I would find out what are the obstacles are on the patient side…. I would explain to them that the CAR T…still represents their best option. So, if it’s a logistic problem or socioeconomic problem, I try to solve that for the patient, for them to be able to go to what, I consider, a superior treatment. If they’re not eligible because of their poor performance status, they’re too old, or the disease is too far gone, then I would accept that as maybe the patient is not suitable [for CAR T-cell therapy]. But if it’s still something else other than a medical reason, I would try to convince the patient that they should pursue this therapy.

MUJAHID RIZVI, MD: In this situation, do you use bendamustine [Bendeka]? Because you always wonder if maybe 6 months from now the patient may change their mind.

TUSCANO: I struggle with that. If I could avoid it, I would. Now, some people are adamant about it. Some people say, “Maybe I’ll consider it later, unless there are comorbidities.” You want something that’s well tolerated for their comorbidities, performance status, and age. [Other factors that impact treatment include their] financial considerations, or convenience of treatment by being able to stay close to home and family. Sometimes they just don’t want to do it. They don’t want to go to a big academic center and get intensive therapy. So, there’s a balance, and there’s a fine line we all walk with patients. We want to listen to them, but we want to do what we feel is right for them as well.

^Reference:

^{Duell J, Abrisqueta P, Dreyling M, et al. Five-year subgroup analysis of tafasitamab + lenalidomide from the phase II L-MIND study in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2023:41(16):e19522-e19522. doi:10.1200/JCO.2023.41.16_suppl.e19522}