Physicians Discuss Roles of Later-Line Therapies in DLBCL

Matthew Matasar, MD, MS

Chief, Division of Blood Disorders,

Rutgers Cancer Institute

Professor

Rutgers Robert Wood Johnson Medical School

New Brunswick, NJ

DISCUSSION QUESTION

• How does the approval of loncastuximab tesirine (Zynlonta) addressed an unmet need in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL)? ​
• In which patient population is loncastuximab most suitable for? ​
• How do you plan to use loncastuximab in the context of other available therapies?

MATTHEW MATASAR, MD, MS: Given the activity, overall response rate of 50%, complete response rate of 25%, median progression-free survival of a year, reasonable safety profile, and treatment that can be administered in the community-based context,¹ do these data [support] the use of loncastuximab in either a post-CAR [chimeric antigen receptor] T-cell therapy patient population or in a patient population of patients who are not suitable for or don’t wish to pursue CAR T-cell therapy?

SANTOSH KUMAR, MD: It’s a good treatment option and is fairly [well] tolerated. I have used it in 1 patient. The experience was OK. Pedal edema was an issue and cytopenias were issues. I didn’t monitor the GGT [gamma-glutamyl transferase].

MATASAR: Outside of a trial, nobody does.

KUMAR: Yes. But I don’t think it causes the CHF [congestive heart failure]. It’s just the pedal edema is bothersome to the patient. We know diuretics help.

MATASAR: You’re right to point out that it’s not cardiac. It is, for some reason, strange third-spacing of fluid. Early and aggressive diuretics do wonders at preventing and addressing the edema. [Are there] any other takes on the data from the LOTIS-2 trial [NCT03589469] in terms of your perspectives on the drug?

ANUPAMA DORAISWAMY, MD: I’m a leukemia [specialist], but with my minimal experience I want to add that it’s another great drug. But in terms of sequencing, whether people would use lenalidomide [Revlimid] plus rituximab [Rituxan] or tafasitamab [Monjuvi] plus lenalidomide, etc—I don’t think selinexor [Xpovio] is a good option, from hearing experts both in the myeloma and lymphoma world because of all the adverse events…. Given that 7, 8, or 9 months in somebody who is already relapsed, is this a pathway to a CAR T-cell therapy in patients who haven’t had CAR T-cell therapy before or is this a pathway to a good BiTE [bispecific T-cell engager]? We have 1 BiTE approved, and many BiTEs to go. Or is this going to be to keep going for that rare patient you might consider allogeneic [stem cell transplant] once in a couple of years?

MATASAR: Yes, the challenge of sequencing is definitely relevant. There are not a ton of data yet to guide those decisions. We have a bit of data for CAR T-cell therapy post loncastuximab now, suggesting that CAR T-cell therapy remains active after CD19-directed loncastuximab.² We have data from LOTIS-2 showing that loncastuximab is active after CAR T-cell therapy, but we don’t have an optimal sequence yet.³ How we’re going to overlay bispecific antibodies in this sequencing challenge is a work in progress.

That being said, it’s nice to have a drug that has activity in high-grade lymphoma. We don’t have a lot of other drugs that have demonstrated activity there. Polatuzumab vedotin [Polivy] doesn’t have published activity in high-grade lymphoma. The high-grade lymphoma activity of bispecifics remains very much uncertain. So even though it’s a relatively small number of patients, it’s nice that this drug has documented activity in that context. Where I prefer this agent is in patients who are post CAR T-cell therapy with high-grade lymphoma.

DISCUSSION QUESTIONS

• For which patients do you consider using tafasitamab plus lenalidomide?​
• Have you utilized tafasitamab plus lenalidomide since its FDA approval?​
• What has been your experience and your patients’ experience?​

MATASAR: Tafasitamab/lenalidomide was studied in a select patient population. Are there situations where you would use it outside of that? Would you consider trying this treatment in primary refractory patients? Has anybody used this regimen in your practices, and what’s your experience been?

KUMAR: I have used it in 2 patients. Cytopenia is an [minor] issue. You [need to] reduce the lenalidomide dose, but it is tolerable overall.

ANITA GUL, MD: Yes. I have seen a patient who was on this [regimen] and he was tolerating it well. Other than mild thrombocytopenia, on and off, he had liver function test elevation while on monotherapy. I don’t know a lot about that. I hold the treatment and then it gets better on its own.

MATASAR: Interesting.

GUL: Otherwise, the tolerance is not an issue. I have seen good response, but the patient’s tumor burden was low to begin with. I would not know how much this would be effective in a patient with high tumor burden.

MATASAR: At ASH [American Society of Hematology Annual Meeting & Exposition] this last year, there was a multi-institutional real-world experience with tafasitamab/lenalidomide presented, suggesting that the activity in a more real-world patient population is disappointingly low.⁴ So I think that probably supports that observation that it may be very good treatment for low-risk disease but probably not preferred treatment for higher-risk disease.

_References:

_{1.Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:10.1016/S1470-2045(21)00139-X}

_{2. Thapa B, Caimi PF, Ardeshna KM, et al. CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy. Blood Adv. 2020;4(16):3850-3852. doi:10.1182/bloodadvances.2020002587}

_{3. Caimi PF, Ai WZ, Alderuccio JP, et al. Efficacy and safety of loncastuximab tesirine (ADCT-402) in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2020;136(suppl 1):35-37. doi:10.1182/blood-2020-137524}

_{4. Qualls D, Buege MJ, Phuong D, et al. Tafasitamab and lenalidomide in relapsed/refractory large b cell lymphoma (R/R LBCL): real world outcomes in a multicenter retrospective study. Blood. 2022;140(suppl 1):787-789. doi:10.1182/blood-2022-167620}