Part 3: Barriers to Loncastuximab Before CAR T-Cell Therapy in DLBCL – Targeted Oncology

DISCUSSION QUESTIONS

DEVA NATHAN, MD: I have different question. Are you willing to replace R-CHOP [rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, prednisone] as the first line? Do you think at some point R-CHOP is going to be pass?

PAOLO CAIMI, MD: I think it probably will be improved upon. There are some [aspects] of R-CHOP that will stay. I still think that cytotoxics have a space for these diseases, and we have to be respectful of their role. I dont think it will be completely pass, but maybe vincristine is not the most important drug. So, its a good question. I think at some point well replace some of the parts of R-CHOP.

DIVIS KHAIRA, MD: I think its very important [to note] that the NCCN [National Comprehensive Cancer Network] doesnt put everything into 1 slot, so then youre arguing with the insurance company. Last week, I was trying to teach the insurance company person some hematology. It was an addiction specialist who was telling me how I should practice hematology. Were getting more and more insurance companies [saying] Peer review this and peer review that, and NCCN said only use 1 drug, and not 2 drugs, and thats become a nightmare in daily life. You went from maybe 1 peer review a month to 4 or 5 for everything, and youre talking to a non-oncologist on the other side.

CAIMI: When you say that they dont put everything in 1 slot, you mean that they include the drugs that you use?

KHAIRA: What they do is, they have level 1, 2, and 3. So, what the insurance company does deny is the level 2 and 3. Level 2 and 3 evidence is no evidence to them. For example, they wont give you obinutuzumab [Gazvya] with bendamustine [Bendeka]. They wont give you this, that, and the other. Youre not going to get JAK2 inhibition unless the patient has more symptoms.

A lot of it is driven by the NCCN, and thats a nightmare now. They make things way too specific. And maybe thats good, because advanced practice providers and nurse practitioners can practice like that, but the rest of us oncologists who have experience can wade through some of this information and make our own decisions. But thats now being driven by the NCCN, and this needs to stop, in my opinion.

CAIMI: I think its still important to bring this up.

DISCUSSION QUESTION

CAIMI: Would you consider loncastuximab either while youre waiting for CAR T-cell therapy, or in a patient for whom youre deciding for CAR T cell since its been demonstrated that they can have a response to CAR T cell afterwards?

YAN JI, MD: I do think these data provided peace of mind. I can see that although the study is small, at least theres a signal that a patient still can respond to CAR T-cell therapy after receiving loncastuximab.

KHAIRA: The question is: Whats the response to CAR T cell after fourth-line therapy? While 46% responded [to CAR T-cell therapy after loncastuximab], if they receive loncastuximab in the fourth-line and they go for CAR T cell therapy afterward, whats the response?

CAIMI: True. I dont think we know that. We know the patients who have more advanced disease tend to have worse [outcomes], and I think thats why comparing loncastuximab to the other 2 drugs that included patients on just 1 line of therapy is not necessarily a fair comparison, because they were sicker patients. I think well learn more as we start treating patients with less advanced disease with these drugs.

NATHAN: To answer your question, how about if you see 24% complete response and 24% partial response? Thats 48% compared with 46% on CAR T-cell therapy, theyre basically equivalent response rates. Can I say it in that way?

CAIMI: Yes, thats true.

NATHAN: Either the patient is too sick to go through CAR T-cell therapy or they are waiting for CAR T cell, then maybe you can use it before. I can see this can be transposed before or after. It makes it a more reasonable drug option.

CAIMI: Yes. So it would potentially be a bridge to CAR T-cell therapy. Thats 1 of the things were looking for, drugs that can get us a patient that can be using CAR T cells afterwards.

[In regard to the] phenomenon where people lose their CD19 expression, how much does this concern youpeople who are getting repeated CD19 drugs?

KHAIRA: Im not so concerned if you have a 46% response. Youre looking at loncastuximab in patients who have been treated with multiple other drugs. The real question is going to be, does it make a difference if you use it earlier?

CAIMI: Youre using drugs that target the same surface markers, which is something to be concerned with.

LYLE GOLDMAN, MD: Were getting away from lymphoma biology, germinal center and non-germinal center. Where do those things factor in when youre thinking about second-, third-, and fourth-line therapies? In the [L-MIND] study of tafasitamab [Monjuvi] and lenalidomide [Revlimid], I noticed that two-thirds of the patients were not classified in terms of germinal center versus non-germinal center subtype.2 And we know that lenalidomide is principally active in the non-germinal center subtype. But how do these other therapies factor in, considering that?

CAIMI: Good question. First, I think that you can see that these studies are reporting it less and less. The second thing that youre seeing is that the drugs are working in both subtypes. And the third thing that you can see is from the large phase 3 studies, that when they tested for cell of origin, those studies were either inconclusive or they werent positive. For tafasitamab/lenalidomide, it seems that it works in a proportion of patients that have the germinal center subtype. It may work a little bit differently; it may not work as well.

Then, it seems that both loncastuximab and polatuzumab [Polivy] are agnostic to the subtype. Which, at least in my opinion, is a good thing, because I think the cell of origin is a square box that were trying to fit our round peg into. I dont think it explains the whole biology of the disease, and I think, sadly, were still stuck with the outside of the cell instead of the inside of the cell. I think that will probably change soon. But thankfully, I think targeting the surface antigens allows us to move away from that thinking, and it works in both scenarios. At least in terms of efficacy for loncastuximab, theres no real difference between non-germinal and germinal.1 The results were comparable.

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. Salles G, Duell J, Gonzlez Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study.Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4

View post:
Part 3: Barriers to Loncastuximab Before CAR T-Cell Therapy in DLBCL - Targeted Oncology