Evaluating Role of Loncastuximab in Third-Line DLBCL After CAR T
During a live event, Krish Patel, MD, discussed barriers to using bispecific T-cell engagers and practical considerations of using loncastuximab in a patient with relapsed diffuse large B-cell lymphoma who had prior CAR T-cell therapy.
Krish Patel, MD
Director of Lymphoma Research
Executive Chair Lymphoma Research Executive Committee
Sarah Cannon Research Institute
Nashville, TN
This article is part 2 of a 2-part series from a Case-Based Roundtable event.
DISCUSSION QUESTIONS
Regarding bispecific antibodies for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL):
- How do you incorporate bispecifics into your treatment approach?
- Are patients treated in the community setting, or do you refer them to academic centers?
- What are the key challenges/access barriers to bispecific therapy?
Krish Patel, MD: As you think more about incorporating bispecifics into your treatment approach, I think many of you mentioned one of the barriers has been CRS [cytokine release syndrome] monitoring. But we also heard that the advent of bispecifics in solid tumors is helping to pave the [way for] its use. Is this something that many of you who are not currently using them are talking about how we how you might implement these therapies in your practice?
Thai Ho, MD: I think if there are opportunities to use prophylactic tocilizumab [Actemra], where they would pay for it ahead of time, that might help limit [CRS so] that you could potentially do outpatient administration as well.
Patel: [Agents] to help reduce the risk of CRS is an approach that is under study in multiple myeloma, including with a focus on outpatient delivery. Others who have considered this for implementation in your practices, what are some of the things you'd want to see to help push that towards full implementation where you're doing the step-up dosing in your own practices?
Niyati Nathwani, MD: [The barrier is] the hospitalization for so many hours. There's a lot of resistance from the admitting doctors and hospitalists at the local community hospitals. If we are able to overcome that and [use] some of the rescue medications, keeping them on hand, I think that would help. Initial step-up dosing is always going to be a challenge unless all these [barriers] are addressed. But for the subsequent doses, I think we are comfortable, especially with epcoritamab [Epkinly]. With the subcutaneous [administration] it's a lot easier. I think that's where our challenge lies, at least.
Patel: There is more to come there. But I think what I'm hearing is, if we can decrease the toxicity and make it even more outpatient friendly, then our experience with these agents as a class improves. Then that seems to be the pathway forward. One of the things that has been a challenge is how much CRS you get with a given bispecific is different in different disease states. If you take myeloma, that tends to be a much higher overall incidence, and then in low-grade lymphomas with drugs like mosunetuzumab [Lunsumio], it’s perhaps lower. I would say bispecifics are not all the same across the board, but one approach may be implementable with modifications for each drug.
DISCUSSION QUESTIONS
- Does the LOTIS-2 trial data (NCT03589469) address an unmet treatment need for your patients with DLBCL?
- Where does loncastuximab tesirine [Zynlonta] fit into the treatment landscape?
Patel: Is this a drug that you think fulfills that a need for those patients you described who are not able to get to clinical trial sites or for bispecifics, if you're not able to give those in your practice?
Govinda Brahmanday, MD: I think it’s a great option. I personally have not had any patients on loncastuximab, but a partner in the group had 2 patients in their 80s and 90s on loncastuximab who did well, and after a few cycles they had a complete response and are off therapies.
Patel: Right, so maybe in that older patient population, in somebody who's got a deep response, it seems like you've found value there. What about other types of patients?
Brahmanday: As a third-line option, it would be a great option for the patients if they cannot…get bispecific or chimeric antigen receptor [CAR] T-cell therapy in the second line.
Venu Madhav Konala, MD: Is this the setting where you test for CD19 and you need to repeat biopsy before you use loncastuximab if you used CAR T-cell therapy prior to it?
Patel: I would love to hear from others what your approach is. CD19 antigen loss occurs in somewhere around 25% or 30% of patients who have progression after CD19 CAR T cells in large cell lymphoma.1 It doesn't appear to be the predominant mechanism of resistance. There may be other factors. One can expect CD19 to be present in most patients. I used to biopsy a lot of patients. I don't think I'd push for it quite as much now, unless we're looking for other potential clinical trial–based options.
Michael Byrne, MD: I still tend to biopsy. I wouldn't do a video-assisted thoracic surgery to get a biopsy, but I think a core biopsy is a minimally invasive procedure. If the lymph node is right in front of my eyes, I still tend to biopsy these people before CAR T-cell therapy. I've given loncastuximab once, and I would probably biopsy before I went down the path of a CD19 antibody-drug conjugate.
Patel: Accessibility of the site makes a big difference. That's an important point.
Konala: Regarding the gamma-glutamyl transferase [GGT] that was monitored in the trial, how important is it to monitor if the liver function is normal?
Patel: I don't monitor it because it was essentially shown to be asymptomatic GGT elevation without any concurrent clinical liver dysfunction.2 In my understanding from the clinical trial, that was a requirement the FDA had for monitoring, but it didn't have any clinical significance. I have not, in clinical practice, monitored GGT. I do look for liver function test abnormalities because those would be actionable, but I don't usually check GGT.
Peter Jiang, MD: For patients with cardiopulmonary disease, are you comfortable using loncastuximab, especially if you’re worried about capillary leak syndrome?
Patel: In my own experience, I haven't had such a scenario. If a patient has very poor ejection fraction and baseline issues with pulmonary edema or congestive failure, that might be a patient in whom you think about using a different agent, because it can be hard to monitor for what is treatment-related toxicity vs the underlying disease. In my experience, usually using the dexamethasone premedication, I haven't run into a lot of issues related to capillary leak, and I think if the patient's cardiac function is reasonably stable over time and well managed, then that can be still a good option.
That would also be a patient who may not tolerate CRS very well. I don't think that necessarily means that they would be better served with a different therapy option. They're going to have a high risk for toxicities with most therapies.
DISCLOSURES: Patel previously reported consulting fees from AstraZeneca, AbbVie, ADC therapeutics, BeiGene, Bristol Myers Squibb, Caribou, Fate Therapeutics, Genentech, Janssen, Kite, Lilly, Merck, Nurix, Pfizer, Pharmacyclics, Sana, and Xencor; received research funding from AstraZeneca; received travel expenses from Lilly; and received payment for lectures from AstraZeneca and Kite.
