Experience and Sequencing Guide Third-Line DLBCL Therapy Selection

Matthew Ulrickson, MD (Moderator)

Chief, Section of Hematology

Banner MD Anderson Cancer Center

Gilbert, AZ

CASE SUMMARY

• A 73-year-old woman presented with fever, headaches, and a 7-lb unintentional weight loss​.
• Family history: married with 2 grown children who live in other states; primary caretaker for her mother who has advanced dementia; no family history of cancer
• Medical history: hyperlipidemia well controlled with simvastatin
• Stage III disease; International Prognostic Index score 2; low-intermediate risk​; non-germinal center
• Laboratory results: lactate dehydrogenase, 265 U/L (upper limit, 280 U/L); hemoglobulin, 10.8 g/dL; bilirubin, 1.1 mg/dL (upper limit, 1.2 mg/dL); creatinine, 1.7 mg/dL (upper limit, 1.2 mg/dL); all others within normal limit​
• Hepatitis B, C negative and HIV negative​
• Lymph node biopsy;immunohistochemistry panel: CD10+, CD20+, which confirmed diffuse large B-cell lymphoma (DLBCL)
• Fluorescence in situ hybridization: negative for rearrangements of BCL6, BCL2, and C-MYC​
• Whole body PET/CT scan showed diffuse adenopathy, largest node 3.9 cm
• MRI of the brain showed no evidence of lesions​.
• ECOG performance status: 1​
• The patient received 6 cycles of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], and vincristine sulfate [Oncovin], and prednisone), which she tolerated​ well.
• She had a complete response (CR) at the end of treatment, but 14 months later she presented with diffuse lymphadenopathy, confirmed by PET/CT scan​.
• Biopsy showed relapse of DLBCL​.
• The patient received 6 cycles of polatuzumab vedotin (Polivy), bendamustine, and rituximab (Pola-BR).
• She achieved response, then her disease progressed 8 month​s later.
• The patient is not able to travel because she is the primary caretaker for her mother, who has dementia. She declined autologous stem cell transplant.
• Current treatment:​ loncastuximab tesirine-lpyl (Zynlonta)

DISCUSSION QUESTIONS

• Do you agree with the treatment choice for this patient?
• What other therapeutic options could be considered?

MATTHEW ULRICKSON, MD: [What are your] thoughts on treatment choice for this patient? What does everybody prefer giving to a patient like this?

CHRISTOPHER CHEN, MD, MBA: I've been pretty comfortable using tafasitamab [Monjuvi]/lenalidomide [Revlimid], albeit at a lower dose of the lenalidomide. Other than the cytopenias, it's physically relatively well tolerated as long as the lenalidomide is not dosed too aggressively, and patients typically have a good response to the treatment.

ULRICKSON: What do you like to start with lenalidomide dose-wise? Or does it depend?

CHEN: I use 10 to 15 mg if I'm brave; I definitely don't do the full dose. The 1 time I did it, I learned not to do it again.

ULRICKSON: Especially for somebody like this. The patient’s creatinine level is 1.7 mg/dL, so it's not too bad, but it can definitely hit hard. Other thoughts on what you would give in this setting? Has anybody else done loncastuximab in this setting?

BRAD HAVERKOS, MD: I've used loncastuximab a fair amount and it has reasonable tolerability. After 4 to 6 doses, even 4 doses, people tend to have adverse events [AEs]; the AEs tend to build, and patients can't stay on the drug for 12 months. But I'd say I've had good success and it's tolerable, just acknowledging the unique AEs that are associated with it of edema and skin photosensitivity. But I think it's a good option.

CAMILLE JOHNSON, MD: I've given loncastuximab as well…. There were some cytopenias and some rashes.

HAVERKOS: There are the bispecifics, [I am] certainly thinking about those in this setting as well.

ULRICKSON: [Those are the newer drugs], but definitely some helpful ones.... In the third-line setting, some of the therapies we have available include the bispecifics epcoritamab [Epkinly] and glofitamab [Columvi]; both are CD20 targeted with the CD3 arm for the T cells. There's loncastuximab, which is CD19 targeted, selinexor [Xpovio], which finds its space in many disease types, and then polatuzumab, which is an anti-CD79b [antibody-drug conjugate].

DISCUSSION QUESTION

• Considering the LOTIS-2 data (NCT03589469), for your patients with relapsed/refractory DLBCL, where does loncastuximab fit into the treatment landscape?

ULRICKSON: Do you think that loncastuximab has a helpful place in the third line? Where would you use it?

HAVERKOS: The decision is usually [for a] patient who is post CAR [chimeric antigen receptor] T-cell therapy or in the multiple relapse setting. The choice is whether to use a bispecific or loncastuximab, and I'd say that for lack of a better way to choose, I usually decide based on CD19 or CD20 expression. If they had previously seen a CD19-directed CAR T-cell therapy and they're CD19 and CD20 positive, I tend to prefer a bispecific, targeting a different antigen there. That's my rationale.

_Reference:

_{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}