Rounds with the Investigators 2012 | Multiple Myeloma
QUESTION: A 79-year-old lady, multiple myeloma IgG lambda, diagnosed in April 2010, initially IgG 7,650 mg/dl (700-1,600), free Kappa 13.2 mg/l (3.3-19.4), free Lambda 10.000 mg/l (5.7-26.3), free Kappa/Lambda quotient <0.01 (0.26-1.65), creatinine 3.41 mg/dl (0.5-0.9), Hb 9.4 g/dl (12-15.6), thrombocytes 89/nl (150-370), BM biopsy: approx. 80% plasma cells. Treated with VMP. After 6 cycles IgG 435 mg/dl, creatinine 1.7-2.1, Hb 11g/dl, thrombocytes approx. 100/nl. No severe toxicity except intercurrent hematotoxicity Grade 3 to 4. She then showed signs of a cold with rhinitis. After a week she came back with creatinine of 6-7 mg/dl (UNL: 0.9), Bence-Jones proteinuria of more than 5g/l. First she had polyuria then oliguria and now she is under dialysis thrice/week. BM biopsy: approx. 90% plasma cells, anemia with Hb 8g/dl and thrombocytopenia with thrombocytes between 12-30/nl. What would you recommend as 2nd-line chemotherapy?
DR JEFFREY ZONDER: I would probably, for this lady, be thinking about renally dosed lenalidomide and actually switching from melphalan to cyclophosphamide for her. There’s not complete cross resistance between those. That was showed in older literature. And perhaps we could get some disease control.
The other question that would be hanging out there is whether or not it would be worth trying to continue some dose, some schedule of bortezomib along with this, based on the fact that she has renal insufficiency. And again, you’re kind of recycling, except for the addition of an immunomodulatory drug, you’re sort of recycling classes of drugs that have already been used, and you’re hoping for synergy. And she’s 79.
DR NEIL LOVE: I’m not sure how easy it is to access lenalidomide in Germany. What about thalidomide?
DR ZONDER: You can certainly use thalidomide. I mean, there’s large-scale data, obviously, from Europe on thalidomide/cyclophosphamide and dexamethasone.
DR LOVE: Raymond?
DR RAYMOND LOBINS: Yes. When I get recurrent patients like this, the biggest problem I have is their platelet counts. And this lady has a very low platelet count. I know you have to do what you have to do, but bortezomib lowers platelet count and so do the IMiDs. Does that weigh into how many you use or how aggressive you use?
DR ZONDER: This is a 79-year-old woman with dialysis-requiring renal failure. And so it’s hard, from an email, to understand what kind of physical specimen she is and what she can tolerate. But let’s take that out of the equation. Let’s just make her a 59-year-old patient, and this is the scenario. And so what are you trying to do to get disease control? When I am consulting on such a patient, if the patient is going to be treated by the community physician that referred them, my specific advice is: Dig in. This is going to be like a leukemic patient, perhaps, in terms of the counts for a little while. You’re going to have to go into therapy with the expectation of having to support them and not pull up on dose intensity just because the counts get uncomfortable. You have to support them with transfusions.
DR LOVE: Chuck?
DR CHARLES FARBER: That would be a reason, probably, why you’d favor thalidomide over lenalidomide — because of the cytopenias, less cytopenic side effects with thalidomide.
DR ZONDER: Perhaps. Yes. But it’s also probably not as active of a drug, I think.
DR LOVE: Jeff Wolf, anything for Dr Van Anh?
DR JEFFREY WOLF: Yes. I’d like to go back. I don’t think it’s enough to know that it’s just VMP. I’d like to know how much bortezomib and, going back to our previous discussion about melphalan or phenylalanine mustard versus cyclophosphamide, I’d probably go after this patient with weekly cyclophosphamide. Maybe you said that.
DR ZONDER: Yes. I would add lenalidomide and weekly cyclophosphamide.
DR WOLF: Yes. I would do that.