During a Case-Based Roundtable® event, Emily Ayers, MD, discussed the current landscape for the treatment of patients with diffuse large B-cell lymphoma, the need for better risk stratification data, and what led to the approval of loncastuximab tesirine in the first article of a 2-part series.
CASE
Targeted Oncology: What is the current landscape for the treatment of patients with DLBCL?
EMILY AYERS, MD: In the first-line setting, patients who are transplant eligible should be treated with chemoimmunotherapy.1 Some of the recommended regimens [for these patients] include R-CHOP, rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP], and polatuzumab vedotin [plus] R-CHP. Then in the second-line setting, the major branch point is the [patient’s] time to relapse, so whether the patient relapses early, within a year of their first-line therapy or late. In addition to that, whether they are transplant eligible or ineligible.
For those patients who had a late relapse and are transplant eligible, they often get second-line salvage immunochemotherapy. For those patients with chemotherapy-sensitive disease, they end up with stem cell transplant. For those patients with early relapse disease, some of the new data from a couple years ago demonstrates that chimeric antigen receptor [CAR] T-cell therapy for patients who are eligible, and have access [to it], should be the standard of care.2
How do these treatment considerations change if the patient is transplant ineligible?
For those patients who are transplant ineligible, there is a CAR T-cell product they can get, but a lot of these patients end up either getting rituximab with chemotherapy in the second-line setting, or additional non-chemotherapy based options that are approved in this setting.1 In the third-line setting and beyond, some of the recent advances over the last few years include CAR T-cell therapy, tafasitamab-cxix [Monjuvi]/lenalidomide [Revlimid], polatuzumab vedotin-piiq plus or minus bendamustine/rituximab, loncastuximab, selinexor [Xpovio], which is an oral therapy, and pembrolizumab [Keytruda] for patients with primary mediastinal large B-cell lymphoma.1 Ibrutinib [Imbruvica] is used in some select cases, and 2 different bispecific antibodies that were recently approved [are used in some cases] as well.3,4
How does the IPI and other risk stratification measures factor into treatment decisions?
There are several different IPI scores, as this is how we risk stratify patients [with DLBCL] in the first-line setting.1 The IPI scores date back many decades at this point to the early 1990s, and the standard IPI has 5 different factors to it including, age, LDH, performance status, disease stage, and extra nodal involvement at more than 1 site.1 Then, you can risk stratify patients, according to the number of risk factors that they have into low, low-intermediate, high-intermediate, or high [risk categories].1
What other risk stratification methods are there to consider?
Over the last few decades, there have been several different ways that this has been changed. There's an age-adjusted IPI for patients younger than the age of 60;5 there’s also a stage modified IPI score,6 and then there is the NCCN IPI score that...further subdivides age and LDH into 3 different categories instead of just 2 categories, and you have a risk score from 0 to 6 in this setting.7 The Pola-R-CHP [regimen] has the approval for IPI 2 and beyond, so I sometimes calculate [risk] in that setting, but I have not adopted the updated IPIs for whatever reason. I think that we can do a lot better in terms of risk stratifying patients up front with molecular data.
What led to the FDA approval of loncastuximab in DLBCL?
Loncastuximab was approved following the...phase 2 LOTIS-2 study [NCT03589469], which included patients with relapsed and refractory DLBCL in the third-line setting and beyond.8,9 [To be eligible for the trial], patients had to have at least 2 prior lines of therapy.9 Patients who had prior CD19-directed therapy did have to have a biopsy to prove CD19 positivity prior to treatment on the study; they also had to have a good performance status and patients were allowed [on the study] if they were either transplant eligible or ineligible. [Patients were enrolled on the study] at least a month after their transplant, or 60 days after allogeneic transplant.9
Of note, they allowed patients with primary refractory disease as well, which is different compared with the L-MIND study [NCT02399085].10 Loncastuximab was given every 3 weeks for up to a year. It is a finite treatment and is not given until disease progression.9 [Patients were given] a dose of 0.15 mg/kg for the first 2 cycles, and then the dose droped down [to 0.075 mg/kg] for all subsequent cycles. The primary end point [of the study] was overall response rate with secondary end points including duration of response, complete response rates, and then survival and safety data.9
References:
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