What is the Best Dose of Lenalidomide? Lunning Provides His Analysis in R/R 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.​

DISCUSION 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?

How does the use of tafasitamab (Monjuvi) and lenalidomide (Revlimid) impact your practice?

MATTHEW A. LUNNING, DO: When giving tafasitamab and lenalidomide, do you look at the patient's creatinine clearance to help inform what dose of lenalidomide to start at?

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: To start the dose, I'm [looking for a] normal creatinine clearance and if there's a low creatinine clearance then I adjust to a much lower dose. But even for a patient with a normal creatinine clearance I don't go above 15 mg [of lenalidomide].

LUNNING: So you're apprehensive to use the full 25 mg [dose] that was used in the L-MIND trial [NCT02399085]?¹

MUSHTAQ: I have seen that if you use more than 15 mg of lenalidomide then cytopenias could be a big challenge.... I've never tried 25 mg, but I've used 20 mg [of lenalidomide] with tafasitamab for my first patient and I had a pretty bad experience. So, I've stuck to 15 mg for now.

LUNNING: I've also used tafasitamab and lenalidomide, but...when I first used it, I was a little bit apprehensive to use the 25 mg [dose of lenalidomide]. What piqued my interest was if [my patient's met the characteristics of those on the] L-MIND trial, because the data showed that about 80% of the patients could stay at a 20 mg dose or higher.¹ I was curious whether it was something about the tafasitamab that was allowing them to stay at higher [lenalidomide dose].

I'm not afraid to give it to a patient who has a creatinine clearance less than 60 ml/min, but I certainly dose reduce the lenalidomide. In my experience, there's a right dose of lenalidomide for everybody and it might not be 25 mg, and you find that out quickly, but sometimes you just [feel out] what the right dose of lenalidomide will be.

MUSHTAQ: Say you go below 15 mg of lenalidomide, are you then compromising the efficacy [of the drug]?

LUNNING: It depends on why you're reducing the dose [for the patient], but also it depends upon what their response is. As you're [reducing the dose], if only have stable disease, then yes, I get concerned about the efficacy. But if they [still have a] complete response, then I'd be more apt to try and keep them on the regimen for as long as possible using dose reductions because of the durability of the regimen. I'm trying to get them to the 12-month mark where I get to drop the lenalidomide anyways, but it is very dose intensive on the tafasitamab side with the commitment to weekly dosing.

LIN HAO, MD: I concur with that. One of the advantages of this regimen is the weekly infusion of tafasitamab.... However, I never start with 25 mg of the lenalidomide, even if the patient’s renal function is normal. I start from 10 mg and then 2 weeks later I increase [the dose of lenalidomide to] 15 mg.

LUNNING: So, you use a myeloma maintenance–like approach, where you dip your toe in the water and if the patient doesn't call you in 2 weeks then you go up to 15 mg [of lenalidomide]?

HAO: That’s correct. I had 1 patient where I stopped treatment...[because of the] severe cytopenia.... With the use of growth factor support, because it's a weekly infusion [of tafasitamab], it's difficult to use pegfilgrastim [Neulasta] and we can use tbo-filgrastim [Granix]. The patient basically has to come to the clinic 3 days a week, and that can be difficult [to manage].

MUSHTAQ: With tafasitamab, the regimen is given more frequently for up to the first 3 or 4 cycles. Sometimes these patients are not candidates for transplant or CAR T-cell therapy, and they're beaten up from the prior line of therapy, which make cytopenias an issue from the get-go. What day of the cycle do you use granulocyte colony stimulating factor [G-CSF] growth factor support, especially [when the patient is] in the first 3 cycles of treatment?

LUNNING: I start G-CSF support early and try to see if I can get them on tbo-filgrastim for use at home. This is in anticipation that there are some insurances that allow you to dose and teach [the patient] to administer G-CSF support at home. If I was going to [give them G-CSF], then I would do it [leading into when I see the] patient again, which would be them coming in for next dose of tafasitamab.... Some of us will wait for the patient to be neutropenic coming in and then [tell the patient] to take the G-CSF for 2 to 3 days, take a break, and then we'll recheck them and dose reduce [the lenalidomide]. I think that's what you do for the first time, but then I'm a little bit more aggressive on the backend if I know that they've had it before. I'll try and get their absolute neutrophil count up as they're coming in for the next dose of tafasitamab.

^Reference

^{Duell J, Abrisqueta P, Andre M, et al. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study. Haematologica. 2024;109(2):553-566. doi:10.3324/haematol.2023.283480}