Rounds with the Investigators 2012 | Multiple Myeloma
QUESTION: How would you treat a patient who has plasma cell neoplasm in the lung and soft tissue and monoclonal spike and negative bone marrow? Initially responded to bortezomib and doxorubicin and dexamethasone for a very short time, then treated with RT with near complete response. Now after about 16 months recurrence in the rib cage and soft tissue and positive IgG.
DR GRACY JOSHUA: So this is a 74-year-old male who presented with a right supraclavicular node enlargement. So at the time he had a CT scan of the chest, which showed extensive adenopathy and, also, a mass in the right thoracic outlet going toward the scapula. Biopsy was done, which showed plasmacytoma.
DR NEIL LOVE: This was biopsy of a node, or what was it a biopsy of?
DR JOSHUA: Biopsy of the cervical node.
DR LOVE: The cervical lesion.
DR JOSHUA: It showed a monoclonal expression of kappa light chain. He was referred to me, and the workup showed that he had an IgG kappa monoclonal gammopathy. His IgG was 3,740, and he had a normal IGA and IGM. His bone marrow was completely normal. His urine and his skeletal survey were negative. He had no anemia or renal insufficiency.
DR LOVE: Before you go on to his treatment, I want to ask the 2 Jeffs what they’d be thinking. Anything else you want to say about his presentation?
DR JOSHUA: No. He has been pretty good, in pretty good health. He had a blood pressure that was well controlled. Other than that, he had no other previous illness.
DR JEFFREY WOLF: Gracy, I’m sorry. How old?
DR JOSHUA: Seventy-four.
DR WOLF: Seventy-four, and this is a solitary lesion.
DR JOSHUA: He had —
DR JEFFREY ZONDER: There’s other adenopathy, too, though.
DR JOSHUA: — suppression.
DR WOLF: There’s other adenopathy as well.
DR JOSHUA: Extensive, and in the chest. It almost looked like lung cancer with the supra —
DR WOLF: And “in the chest,” what do you mean by “in the chest”? In the mediastinum or —
DR JOSHUA: He has a mass —
DR WOLF: — in the lungs?
DR JOSHUA: He has a mass in the upper outer quadrant of the right lung.
DR WOLF: Contiguous with the external —
DR JOSHUA: Yes.
DR WOLF: — adenopathy. So it’s all one big —
DR JOSHUA: Yes.
DR WOLF: — adenopathy mass. And the biopsy of that was all plasma cells?
DR JOSHUA: Yes.
DR LOVE: What are you thinking, Jeff Wolf?
DR WOLF: Strange.
DR ZONDER: And there were mediastinal nodes?
DR JOSHUA: Not at the time.
DR ZONDER: Not at the time. Okay.
DR WOLF: So this possibly grew out of a bone, maybe clavicle. Or the rib.
DR JOSHUA: It did not involve the bones. The bones were negative.
DR WOLF: And the only adenopathy is in the neck.
DR JOSHUA: It was all soft tissue.
DR WOLF: On one side of the neck?
DR JOSHUA: Yes. On the right side.
DR WOLF: Right side, supraclav —
DR ZONDER: Cervical —
DR JOSHUA: And the chest CT was done, assuming that this was a lung cancer. Chest CT was done and showed a mass in the right upper lobe of the lung, really, but there was a continuation.
DR WOLF: So it seems like it’s all —
DR ZONDER: It’s one mass.
DR WOLF: — one contiguous —
DR JOSHUA: Yes.
DR WOLF: — mass. Right neck, right superclav, right apex of the lung —
DR JOSHUA: Yes.
DR WOLF: — all the same. Possibly, I would think bone, evolved from a bone.
DR JOSHUA: It wasn’t —
DR WOLF: You might not know that, but —
DR JOSHUA: It did — the CT scan did not show any bone —
DR WOLF: In early-stage myeloma — and maybe Jeff’s seen it or maybe the people at Mayo have seen it, because they see so many — you rarely see nodal presentation, that this, I believe, is probably bone based.
DR ZONDER: Or it’s soft-tissue plasmacytoma, which is uncommon, but I mean, yes — it sounds like this is a solitary plasmacytoma.
DR WOLF: So if PET scan’s normal everywhere else —
DR ZONDER: Bone marrow biopsy was normal?
DR JOSHUA: Yes.
DR WOLF: Bone marrow biopsy normal.
DR ZONDER: Solitary —
DR WOLF: You can treat it as a solitary plasmacytoma, which means, in this case, long-course, high-dose radiation.
DR WARREN BRENNER: But they had a high M-spike.
DR WOLF: Could be from the tumor, and you’d see what hap —
DR BRENNER: But aren’t those patients at much higher risk for developing systemic myeloma?
DR ZONDER: And you’d follow it, I mean. And there’s no other measurable disease elsewhere to account for that, and there’s no other measurable or identifiable systemic disease to treat. I probably would also favor treating this as a solitary plasmacytoma.
DR WOLF: You have — the patient’s 74. Right?
DR JOSHUA: Yes.
DR WOLF: So you have this opportunity to treat it as a solitary, knowing that most solitary plasmacytomas eventually are not really solitary. But in this case, call it a solitary, treat it solitary and watch the M-spike. It may go away or it may persist. If it persists and grows again, you’ll be looking for another lesion, maybe with an MRI as well. We can do whole-body MRI. I don’t know about you.
DR JOSHUA: I could. We do.
DR WOLF: No. It’s a single session. It’s an hour. It really quite nice. Yes. It’s not like different parts. But, anyway, I think you treat it as a solitary plasmacytoma.
DR LOVE: Ray?
DR CHARLES FARBER: Could this be a lymphoplasmacytic lymphoma with a paraprotein?
DR WOLF: But you tell me the histology —
DR ZONDER: Usually an IGM.
DR WOLF: — is a mature plasmacytosis.
DR FARBER: They’re typically IGM, but I —
DR JOSHUA: This is an IgG.
DR FARBER: And IgGs.
DR LOVE: What about the histology, Chuck?
DR WOLF: Histology will be more lymphoplasmacytic and, actually, the surface markers will be slightly different than a pure plasma cell lymphoma.
DR JOSHUA: This was a plasma cell. Plasma cell.
DR WOLF: Pure plasma cell and not —
DR JOSHUA: Yes.
DR WOLF: — lymphoplasmacytic?
DR JOSHUA: No.
DR LOVE: Raymond?
DR RAYMOND LOBINS: What about the mediastinum? You said there were some mediastinal nodes. Did you ever think about biopsying those?
DR LOVE: Yes. Why don’t you bring us up to date? Can you bring us up to date on him?
DR JOSHUA: Okay. So he was treated with weekly bortezomib and dexamethasone. The mass did not change. His IgG started increasing. So I put him on bortezomib/doxorubicin and dexamethasone. In 2 months, his IgG came down to 1,800. The neck mass reduced almost to nothing. I continued him on the treatment, and then I saw the IgG going back up again.
And as repeat CT at that time showed that now there was adenopathy and — which had increased from — enlarged adenopathy compared to previously. At that time, I referred him for radiation therapy.
DR WOLF: So the new adenopathy is distinct from the old, or just a regrowth of the old?
DR JOSHUA: So what happened was the lesion decreased in size, couldn’t feel it, almost couldn’t feel it. And then started to go back up again very quickly. And he had a very brief response and then started to go back up again. So at that time the CT scan showed that the mass had also increased in size, but there was, in addition, adenopathy in the mediastinum.
DR LOVE: I see that he got lenalidomide, also?
DR JOSHUA: Not until then. No.
DR WOLF: So I still would have led with radiation and then, if I saw the protein going up, I would have added the therapy. But I think at this point you do need to radiate the bulk disease, because you’ve used some of your best therapy — granted, you haven’t used an IMiD yet, and you haven’t used an alkylator yet.
DR LOVE: Just to be clear, this says he got lenalidomide and dexamethasone and the mass continued to increase in spite of that. Is that what happened?
DR JOSHUA: Right. Very short.
DR WOLF: Yes. So what I’m saying is that you only have a limited number of drugs that work in this disease. So if your proteasome inhibitor isn’t working and steroids aren’t working, you’ve got to use radiation. It’s a very good modality, and then you want to consider an alkylator and, perhaps, an IMiD.
DR FARBER: Yes. I know I’m persisting on this. It’s behaving like a lymphoma. Is this CD20-positive? I know some myelomas can be.
DR JOSHUA: It’s not CD20-positive.
DR FARBER: It’s not CD20-positive.
DR JOSHUA: No.
DR ZONDER: But I agree with you. I would — could this be like a marginal-zone lymphoma with extreme plasmacytic differentiation or lymphoplasmacytic lymphoma?
DR JOSHUA: It was not.
DR ZONDER: It’s a very odd presentation.
DR JOSHUA: Yes. It was not. It was sent out for a second opinion on the pathology and —
DR FARBER: And the drugs you’re giving would be active, I think, across the board in a low-grade lymphoma, including bortezomib and lenalidomide.
DR WOLF: Bortezomib is mildly —
DR FARBER: Doxorubicin.
DR WOLF: — active. And certainly doxorubicin and steroids are appropriate for lymphoma, yes.
DR JOSHUA: So the radiation induced a complete near response, and the immunoglobulin remained normal. At that point he didn’t want to have anything else done. So we waited about 14 months — I was following him.
For 14 months he had remained stable. His disease remained stable, gradually IgG started to go back up, and at that time a repeat CAT scan of the chest showed a recurrence of the mass in the same area where he was radiated.
DR WOLF: How much radiation did he get the first time?
DR JOSHUA: I think he was radiated a full dose.
DR WOLF: What’s the full dose? I’m sorry to ask you that, but there are people —
DR JOSHUA: It wasn’t a short-term high dose that you were talking about.
DR WOLF: Right. So we’re really talking about 3 approaches with radiation. The short-course high dose that we’ve talked about here, maybe 400 times 2 or 800 times 1 or something like that, is used just to palliate in a local area.
DR ZONDER: Good for bone that you can target without a lot of associated soft-tissue toxicity around it. So, like a clavicle or rib, an arm. I mean, that’s a great situation for that kind of radiation.
DR WOLF: And then the 2,400 dose, which is given over perhaps 12 doses, 200 centigray each dose, that is a more historical approach to palliation that could have been used. But then in areas that aren’t critical, like spine or brain, you could actually go to 4,000 or 4,800 and get total control. So you may still have room for more radiation, is what I’m saying. Jeffrey?
DR ZONDER: That’s actually — I think it’s going to be hard to do a second course in a previously radiated area. Right? So the goal of radiation therapy probably changed based — from — initially, if it was localized to here, right, we would have used the dose of 4,500 with curative intent.
DR JOSHUA: I think that was what was used on him.
DR ZONDER: Okay. But maybe not. It might be worth checking, because by the time it was used, this was a recurrent disease with —
DR WOLF: With disease elsewhere.
DR ZONDER: With disease elsewhere.
DR JOSHUA: Yes.
DR ZONDER: And so it actually is quite likely that they used the palliative 20-something hundred. And so while there may theoretically be room to use more radiation, lining up, it’s going to be actually a very complex treatment plan, because of the prior field.
DR WOLF: Right. So what else do you have, Jeff?
DR LOVE: Carfilzomib and thalidomide.
DR WOLF: No, no, no. So, you’ve used an IMiD?
DR JOSHUA: Yes, started —
DR ZONDER: We’ve used an IMiD.
DR WOLF: You’ve used an IMiD. You’ve used an alkylator?
DR JOSHUA: No, I used —
DR WOLF: You’ve used steroids. You’ve used a proteasome inhibitor.
DR JOSHUA: Right. I used a proteasome inhibitor and the dexamethasone initially, but I — it started to grow — IgG started to go back up and the recurrence happened, and I used lenalidomide and dexamethasone.
DR WOLF: And what happened?
DR JOSHUA: And he’s not responding to that. His IgG continues to go up. And now he has developed another soft-tissue mass on the back.
DR WOLF: So this may be the time — and the creatinine’s okay?
DR JOSHUA: Yes.
DR WOLF: PACE. This might be the time to put him in the hospital and give him
platinum/doxorubicin/cyclophosphamide/etoposide.
DR ZONDER: VD-PACE.
DR WOLF: VD-PACE?
DR ZONDER: Yes. But this is also — I mean, we looked at bendamustine and lenalidomide.
DR FARBER: I was just thinking bendamustine.
DR ZONDER: Yes, bendamustine and lenalidomide, although you have to attenuate the doses of both, because both of them cause significant myelosuppression, and particularly together. But we have a very high response rate. It was at times almost — our definition of dose-limiting toxicity — I mean, we expected a lot of cytopenias, and we got it. But if you can support somebody through that, very high response rate, much higher than you would expect with lenalidomide by itself in the relapsed setting.
DR FARBER: Would you ever consider — because this is kind of not a typical case, maybe rebiopsying it to see maybe if the plasma cell component’s gone, maybe, or something underlining that, that maybe this isn’t all what it seems to be and maybe could be a lymphoma? The reason that I was thinking bendamustine may be a good drug for this patient, I was thinking as well, because this could be a hidden lymphoma.
DR LOVE: Bendamustine, what’s the activity in myeloma?
DR WOLF: It’s more than you would think. It’s been good. Jeffrey has more experience than I do.
DR LOVE: You’ve used it?
DR ZONDER: Yes. I’ve used it, and it works. Yes.
DR BRENNER: I just had a patient about sixth line who failed PACE. And is responding to bendamustine alone.
DR JOSHUA: So that’s what you would use, bendamustine alone or —
DR WOLF: We’re giving you some options. And it would be easier to see the patient. But your picture, this picture is very, very, very unusual, out at the extreme. I’d like to know what the FISH was. This may be a 17p or 1Q21, somebody who’s going to do poorly no matter what you do at this point. But your options would be PACE, VD-PACE, like we just discussed, or bendamustine. And you better leave here with multiple suggestions, because they may not work, and you may want to go to your second and third option.