A 64-Year-Old Man with Diffuse Large B-Cell Lymphoma - Episode 1

Case Presentation: A 64-Year-Old Man with Diffuse Large B-Cell Lymphoma

Matthew Lunning, DO, FACP, presents the case of a 64-year-old man with diffuse large B-cell lymphoma (DLBCL) and shares his initial impressions.

Case Overview: A 64-Year-Old Man with Diffuse Large B-Cell Lymphoma (DLBCL)

Case History

June 2020: A 64-year-old man presented with DLBCL

Stage III disease

ECOG PS 2

Serum LDH=3.7 x ULN

NCCN-IPI score=6 (High-risk)

History of hypertension (well-controlled)

Patient does not harbor MYC, BCL2, or BCL6 rearrangements

July 2020: Patient began treatment with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) induction therapy

Patient had neutropenic fever and limiting fatigue that was controlled with growth factor support; also had mild neuropathy

Underwent interim CT scan after 3 cycles/9 weeks and again at completion of therapy (6 cycles/18 weeks)

Patient achieved a metabolic complete response at 18-week PET-CT scan

May 2021 (6 months post–RCHOP completion): the patient complained of recent weight loss, fatigue

Followup CT scan revealed that the patient had relapsed disease

Patient started salvage chemotherapy with R-GemOx (rituximab, gemcitabine, oxaliplatin)

Most Recent Follow-up Notes/Labs

November 2021: 6-month for-cause CT scan and subsequent biopsy revealed that the patient was refractory to GemOx

The patient lives 50 miles from a healthcare facility that administers CAR T-cell therapy and does not have reliable transportation or continuous caregiver support; he and his clinician decided to start 3rd-line tafasitamab/lenalidomide

April 2022: The patient remains on tafasitamab/lenalidomide; fatigue has mostly resolved

Matthew Lunning, DO, FACP: Hi, my name is Matthew Lunning. I’m from the University of Nebraska Medical Center and I’m here with Targeted Oncology™ to talk about a case of diffuse large B-cell lymphoma. This is a 64-year-old man who presented with stage III diffuse large B-cell lymphoma. What’s interesting about this situation is patients with diffuse large B-cell lymphoma can present with all different flavors of their disease.

In this individual, their disease was causing them to have significant reduction in their performance status. They had been quite an active individual, but with the onset of their large cell lymphoma, their performance status declined. At the time of diagnosis, their performance status was 2. They had an elevated LDH [lactate dehydrogenase], which was nearly 4 times the upper limit of normal. Based on their NCCN [National Comprehensive Cancer Network]–IPI [International Prognostic Index] score, they were high risk with a total score of 6. Looking into their past medical history, they had hypertension but no other comorbidities of interest. Their hypertension was well controlled.

At the time of diagnosis, it was felt that there was significant disability due to the disease. We felt very confident that if we could get the disease under control, this individual could hopefully return to their prior performance status 6 to 12 months from their diagnosis. In this setting, there was no MYC, BCL2, or BCL6 rearrangements, so this wasn’t a high-grade B-cell lymphoma with double-hit or triple-hit biology.

Given these findings, despite the high-risk IPI score and the fact that the patient didn’t have double-hit or triple-hit biology, he was started on R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy. This was given at full dose because his performance status was mostly driven by the disease and not necessarily because of any underlying comorbidities. During the induction therapy, he had some issues with toxicity related to the neutropenia. He had neutropenic fever and was given growth factor support with subsequent cycles of therapy. There was also the onset of fatigue that limited giving the regimen on an every-3-week schedule that we’d prefer, as well as some mild neuropathy.

Fortunately, after 3 cycles, a CT scan in the interim portion showed a very good response based on CT criteria. After 6 cycles of R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] via a PET [positron emission tomography]–CT, there was evidence of a metabolic complete remission based on the Deauville scoring system. At that point, he was transitioned from the chemotherapy portion into active surveillance, where we’d see him every couple of months and reassess physical examination, how they’re doing, and laboratory values.

In my practice, I don’t do surveillance imaging routinely in those who are in a complete remission. I ask them how their symptoms are. I’m very mindful to tell them that if they have any symptoms even reminiscent of when their disease was starting, one of the goals is that if they’re going to relapse, to never to let them get as sick as they were at the time of their primary diagnosis. In this case, about 6 months later, shortly after the completion of the induction R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] therapy, they called in with complaints of recent unintentional weight loss and fatigue that they were having difficulty discerning whether it was a lagging chemotherapy fatigue or the fatigue that was driving them down at the time of their diagnosis.

Given that I don’t do surveillance imaging, I’d consider this for-cause imaging. A follow-up CT scan unfortunately demonstrated that there was likely evidence of relapsing disease. We got a biopsy because, very rarely, you can have retrograde transformations. We got another biopsy confirming diffuse large B-cell lymphoma. At that time, we had a long discussion about whether they’re a transplant candidate. I take into consideration not only the disease at the time of diagnosis but the tolerance to the frontline therapy. Basically, we wanted to consider our treatment options to go either toward transplant or against transplant, with my reservations about whether they’d be a transplant-eligible candidate given their prior induction experience.

In this setting, they were given R-gem-ox [rituximab, gemcitabine, oxaliplatin]. I like this regimen when I’m on the fence about transplant eligibility. Because if the patient goes into complete remission and their performance status improves, then you could consider consolidating with an autologous transplant. Whereas if they have chemotherapy-refractory disease, then you’d move on to potentially a third-line therapy.

With the recent approval of axicabtagene ciloleucel in the second line in the CAR [chimeric antigen receptor] T-cell space, that throws a wrinkle here regarding patients who have relapsed within 12 months. Unfortunately, with a couple of cycles of R-gem-ox [rituximab, gemcitabine, oxaliplatin], the patient’s disease was growing, his symptoms didn’t improve, and his neuropathy was slightly worse, so he wasn’t a candidate for consolidative stem cell transplant. We had a long discussion. The patient lived 50 miles away from a health care facility, didn’t have reliable transportation, and was unable to obtain continuous caregiver support. That made it very difficult to give CAR T-cell therapy. At that time, we had a long discussion about next lines of therapy, and the patient decided to proceed to third-line tafasitamab-lenalidomide. At this point, the patient remains on tafasitamab-lenalidomide and his fatigue has mostly resolved.

Transcript edited for clarity.