DR EVENS: So 88-year-old white man presents with severe facial pain. He was found to have Stage IV-E diffuse large B-cell lymphoma with his primary bulk of disease being about a 6- to 7-cm erosive mass that was infiltrating the floor of the maxillary sinus, actually resulting in complete opacification of that sinus, the right frontal, and ethmoid sinus.
He had discordant bone marrow involvement. In other words, he had small cells in the bone marrow. The other pathologic data, MYC was negative, Ki-67 was approximately 40 to 50%. His performance status at the time — really, he had had this for about a month — was 1, leaning on 2. But despite his age, this was a gentleman living on his own, performing all activities of daily living. He did have some comorbidities. He had a history of diverticulosis, BPH, had a history of MI. His baseline ejection fraction is 50 to 55%, although completely compensated, no history of failure. He also had prostate cancer, a Gleason 7, status post orchiectomy 1 year prior. That’s the comments.
DR LOVE: So Mike, what would you be thinking about in this situation?
DR WILLIAMS: Yes. So first of all, I’m thinking we’re seeing a lot of really old patients here today, discussing. That said, it sounds like he’s a candidate for therapy. He’s certainly got very symptomatic disease. He needs to respond well. If he’s got good cardiac function, I would think about the rituximab plus miniCHOP or reduced-dose CHOP as the GELA group reported. He’s not going to be a good candidate with that area of involvement for radiation, which I suppose you could do some version of to palliate it, if he were not a chemotherapy candidate. He’s certainly got a risk for CNS disease, if he doesn’t already have dural-based abutment or extension, given what you were describing about the extent of sinus involvement and infiltration.
So I would think about trying to — I would be going into this thinking this is a palliative approach, but to get something into him that’ll give him some dramatic relief and maybe some degree of disease control for a time.
DR EVENS: And I just — I mean, the baseline, I think, obviously you have to be in the room. He was a guy that was definitely a chemotherapy candidate. He said, “I want to do anything possible” type of attitude, “Give me your best shot” type of approach.
DR LOVE: Chris?
DR FLOWERS: So like Mike, I would think about the rituximab/miniCHOP regimen for this type of patient. Oftentimes when I give that regimen to patients into their eighties, I’ll give it in the hospital and I’ll give it as a sequential regimen the first time, giving the rituximab and then waiting a day or so to see how people do, and then giving the other chemotherapy agents following that. For this particular gentleman, I would think very carefully about the Adriamycin with each cycle and would be willing to drop it later on in the chemotherapy if he started to have trouble.
DR EVENS: So I can tell you the best thing we did for him initially is, frankly, gave him steroids. And the reason I think I’ll see that sometimes even with colleagues in the community, sometimes with someone, especially localized, very symptomatic disease, there’s a feel to rush into radiation up front or to rush into chemotherapy. But often the best palliative modality you can give — so literally 100 mg of prednisone, it was night and day. I mean, his performance status went from 1 to 2 to — I mean, his pain wasn’t gone, but it was markedly improved. And there’s actually data to support that anecdote.
So that was something we did a concerted effort, really to kind of almost like a prephase. We gave him a week of steroids, didn’t give him vincristine and actually gave him a dose of rituximab. You could argue, did we really need that? And it did dramatically improve his performance status.
DR LOVE: Any change in the tumor?
DR EVENS: It was tough to say. I mean, it was really socked in there and pretty hard to see. It looked like it was a little smaller. But we were a little concerned, and maybe I might have minimized his cardiac status, but I was a little nervous to give him anthracyclines. So I think it’s still unpublished, but there’s data from British Columbia, this C-OP regimen, basically substituting etoposide from anthracycline. So we went that route.
The first day’s IV. The next 2 days are oral. And he did remarkably well. He tolerated 6 cycles of R-COP. We vacillated on the intrathecal question, but we figured, gosh, if we’re going to cure this patient of diffuse large B-cell — relatively speaking, “cure” — at least buy him another 5, maybe 10 years. We wouldn’t want a secondary CNS relapse, so we did give him 4 doses of intrathecal. And he did so well and he’s basically asymptomatic, frankly. I mean, a little fatigue at the end of chemotherapy. We consolidated with radiation.
DR LOVE: Hmm. Intrathecal therapy in this 88-year-old man. Chris, agree?
DR FLOWERS: I think it’s challenging. One, I think with anybody with disease that close to his CNS, you want to at least sample his CSF to know whether or not he’s got CNS involvement. Clearly, if he’s got CNS involvement, he’s likely to become symptomatic from that CNS involvement. And you’re going to need to treat it.
CNS prophylaxis is a difficult topic for diffuse large B-cell as a whole. And we could have a whole separate session debating. In an 88-year-old guy, I think one of the things I’d have to think about is, what are you prophylaxing him for? And presumably, that’s to prevent CNS relapse at some point down the road. If you think that your therapy is palliative at best, then I would be less inclined to do CNS prophylaxis.
DR EVENS: See, we were taking the tack that this wasn’t palliative.
DR VOSE: Curative.
DR EVENS: Granted he was 88. Since we were treating him with curative intent, and it only takes one case. I mean, I’ve seen 2 in the last 10 years, of maybe not 88, but over 80, who relapsed. And when you see CNS relapse, it’s within the first 12 to 18 months. It’s horrible. It’s very difficult to salvage anybody, much less an older. So there’s not data to support it, obviously, in this age group. And you could argue, well, should we give intravenous methotrexate instead of intrathecal? We didn’t think he could tolerate that. I’ve typically done that more in patients who warrant, for more than one extranodal in LDH, but we just decided this was kind of the best of both worlds, so to speak.
DR LOVE: Mike, any thoughts about CNS prophylaxis in general and this man, in particular?
DR WILLIAMS: So in general, we certainly do use it for the usual indications. And this would certainly be an indication for it. I mean, I think there’s a chance of curing this patient, but in the fact that we know now that he got through his therapy pretty well, that is better than I would have expected up front. But typically for somebody this age, we tend not to use intrathecal, but we’re up to probably into the seventies, we would certainly do it. And we tend to use 2 to 3 cycles of high-dose IV methotrexate, integrated about day 14 of, say, the odd-numbered cycles, if they’re negative up front, as Jeremy Abramson reported in Cancer, I think, September of 2010.
But older patients, especially once you get past your mid-60s, upper 60s, high-dose methotrexate is not easy and can be quite toxic. So you have to be very cautious about that. But anyway, we tend to use that because there’s a fairly high frequency of parenchymal relapse, not just leptomeningeal. So you sort of cover both things with that. You don’t do the LPs then.
DR LOVE: Julie, any myths or misperceptions that you see about the whole issue of CNS prophylaxis in community-based oncology?
DR VOSE: I would say that a lot of people don’t get it who should get it, number 1. And there is still the issue of, does IT really work or not? That’s an unanswered question. So similar to Mike, if they can tolerate it, we probably would do the IV methotrexate on day 10 to 14. A patient like this wouldn’t be able to tolerate it, I don’t think. So I would have given him IT as well.
DR LOVE: And when you say that people maybe aren’t using anything, what are your usual indications and are there any in particular that you see people not responding to?
DR VOSE: Mm-hmm. So we typically would use IT methotrexate once with each cycle of R-CHOP. And the indications would be kind of orbital lymphoma, sinus lymphomas, anything in the neural access, paravertebral areas. We typically use it for testicular lymphoma. Some people would say if there’s bone marrow involvement and/or high IPI, that that would be an indication. We typically haven’t done that. But there are a lot of places that do do that.
DR LOVE: Chris?
DR FLOWERS: Yes. I think this is exactly the situation where I would give intrathecal therapy, if I were to give it. I just have concerns about giving it in an 88-year-old gentleman. I mean, often, when I have these kinds of discussions with patients, I talk to them about what their life expectancy was from birth. And for a guy who’s 88, he’s probably getting close to that or maybe past his life expectancy from birth. And so we need to weigh that in line with how aggressive to be about his therapy with prophylaxis and other things.
DR LOVE: Just kind of curious, Jon. Do you agree with Julie’s kind of impression that it’s underutilized?
DR FRIEDBERG: I’m a bit more of a nihilist about intrathecal or just CNS prophylaxis in general. We looked several years ago at the SWOG old Intergroup trial before rituximab, which was the CHOP versus ProMACE-CytaBOM versus other regimens. Two of them happened to have CNS active therapy, and 2 of them didn’t. So it’s an opportunity in a randomized way to take a look. And there were potentially problems with some coding of data and so forth, but the bottom line was, we weren’t able to show that the CNS relapse rate was significantly modified by the routine inclusion of CNS prophylaxis. So certainly I don’t think all patients should get it. The event is too low.
So the question is, are there subgroups of patients where you know the risk is high enough where it’s at least worth trying something? And certainly, I think for testicular lymphoma, I do it. And for some of the other situations that Julie described, I do it. But I don’t feel so inclined to do it. Because I certainly agree with Andy, it’s a devastating outcome. The problem is, we have no real evidence that we’re mitigating that outcome with these interventions. And it seems like we should be, except that we’re also potentially causing harm. And therefore, my attitude is, in these situations, I’ll often do it. But if there’s any contraindication, like age 88, I’m certainly comfortable not doing it.
DR LOVE: And “doing it” being intrathecal or IV?
DR FRIEDBERG: I generally use intrathecal. The one scenario where we’ve routinely given IV — and our group decided — was in the testicular situation, where so many of the recurrences are parenchymal. We figured if we’re going to do something, that intravenous methotrexate is the way to go.