Breaking Down Considerations for Tafasitamab/Lenalidomide in DLBCL

CASE SUMMARY

A 67-year-old man presented with fatigue, back pain, and lymphadenopathy​. He had a medical history of hypertension that was well controlled with medication​. A physical exam showed a 1.5-cm eft posterior cervical node, a 2.5-cm right anterior cervical node, and a 2.0-cm left supraclavicular node. A PET-CT scan showed multiple enlarged mesenteric and retroperitoneal nodes, with the largest measuring at 5.3 x 3.1 cm​, but his bone marrow biopsy was negative​. The biopsy still confirmed diffuse large B-cell lymphoma (DLBCL), non-germinal center B-cell, double expressor lymphoma. His immunohistochemistry was positive for CD20, BCL-6, BCL-2 (50% of cells), MYC (> 40% of cells), Ki67 85%, and MUM1​, but negative for CD10​. His disease was classified as stage III with an international prognostic index of high-intermediate risk. He had an ECOG performance status of 1 and ​non-germinal center disease. His fluorescence in situ hybridization was negative for translocations involving MYC, BCL2, and BCL6​.

Six cycles of polatuzumab vedotin-piiq (Polivy) plus rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP) was initiated, and back pain was resolved during treatment. A post-treatment PET scan demonstrated a complete response with a Deauville score of 2, after treatment the patient was observed​. Eight months after completion of therapy, he complained of fever, night sweats, and back pain ​again, and a palpable lymph node in the left groin was discovered on physical examination​. Another PET and CT scan showed a new left inguinal lymph node, increase in size of the residual node, as well as multiple metabolically active lesions in lymph nodes of the retroperitoneum, abdomen, and pelvis​. Biopsy confirmed DLBCL, but next-generation sequencing (NGS) was not performed.​

The patient was referred to nearest transplant and cellular therapy center for evaluation, but ultimately opted not to pursue chimeric antigen receptor (CAR) T-cell therapy.​

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?

LIN HAO, MD: I feel like tafasitamab [Monjuvi] and lenalidomide [Revlimid] is more advantageous, and the response rates are higher [based on the L-MIND study (NCT02399085)].¹ However, it's a difficult regimen [to give and tolerate], especially with the cytopenia. I normally give a dose reduction for the lenalidomide, but even with that approach, my experience is that many patients have severe fatigue and say it's a hard regimen. So, polatuzumab vedotin plus bendamustine [Bendeka] and rituximab [Pola-BR] is gentler, in my experience, but I have used both regimens [for patients like the one in this case]. If the patient has a better performance status and are younger, then I tend to use the tafasitamab/lenalidomide. Otherwise, I tend to consider Pola-BR, but we are in [a phase of] palliative intense treatments [for a patient like this], so the patient will probably need both eventually.

BENJAMIN GEORGE, MD: Where we're practicing is a rural setting, so we're easily 3 to 4 hours away from either Denver, Colorado or Omaha, Nebraska, which means logistics do factor into [how we would treat a patient in a case like this]. Most patients don't like to travel too far, and they like to do as much as they can here with us, although we try to get them out to [an academic center]. But they're older and they're farming, so [at some points in the year] they're harvesting and [it’s on you to] get into their schedule...It's interesting how the logistics are different in the rural setting.

MATTHEW A. LUNNING, DO: From a cellular therapy standpoint, we've looked at our own internal data, and our outcomes were as good if [the patient was] 120 miles away vs [nearby], and that was in the third-line. But that is certainly something we pay attention to, and as an authorized treatment center...the partnership between the community oncologist is important in the cellular therapy space. We're trying to find novel ways to help those patients that you alluded to Dr George, with regards to limiting their visits to a treatment center and keeping them in their bed for as long as long as possible.

Matthew A. Lunning, DO, FACP​Assistant Vice Chancellor of Clinical Research

Associate Vice Chair of Research, Department of Internal Medicine

Associate Professor, Division of Oncology & Hematology

University of Nebraska Medical Center College of Medicine

Omaha, Nebraska

RAO MUSHTAQ, MD: [In my experience using tafasitamab/lenalidomide], you have to be a little bit careful about the dose of lenalidomide. I have used the 15-mg starting dose and I didn't have much issue [with it], but neutropenia is still a big problem with this regimen.

LUNNING: What did you do in regard to handling the neutropenia? Did you dose reduce and use a growth factor support?

MUSHTAQ: I started at a low dose of 15 mg [for a patient like this], and I didn't have to use growth factor support, so there was not a [toxicity problem with this patient]. In the first patient I used growth factor support, [the patient was on] a 20-mg dose and had bad neutropenia, so then I had to reduce the dose down to 10 mg. Then I used the growth factor, but even that didn't help much. Now I just start at a lower dose of about 15 mg each time.

^Reference:

^{Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4}