DR FLOWERS: So this is a 48-year-old African-American woman who presented to me at relapse. But she initially was diagnosed with Stage IV follicular lymphoma based on a right inguinal lymph node biopsy in about 2005 and had disease throughout her neck, chest, abdomen, pelvis at that time and had disease with the largest lymph nodes measuring about 5 centimeters overall and had disease in her bone marrow with about 70% cellularity. She was treated out in the community with 6 cycles of R-CHOP initially that she completed in 2005 and then had restaging PET-CT at that time and a bone marrow that were negative and was just followed without any maintenance therapy or consolidation and then eventually had progression of her disease about a year later in October of 2006.
She got 4 weekly doses of rituximab at that time and then, at that point, chose to receive maintenance, where she was getting a dose of rituximab every 2 months for 2 years and then was followed after completion of maintenance and remained in remission until 2011, when she had progressive disease and had disease in her marrow at that time as well.
DR LOVE: And where exactly did she have disease? How much disease did she have in the marrow? And what was her clinical condition?
DR FLOWERS: So she had, at least by the biopsy she had relatively limited disease in the marrow, what they called about 1 to maybe 5%, but she had lymph nodes that measured between 2 and 4 centimeters in her chest and abdomen and pelvis.
DR LOVE: And symptoms from the disease or quality of life?
DR FLOWERS: She really was relatively minimally symptomatic. This was something that was picked up incidentally on scans by her outside oncologist who was following them over time and noticed that lymph nodes that were measuring about a centimeter to a centimeter and a half had risen in size to about 3 to 4 centimeters.
DR EVENS: How big was the disease, you said?
DR FLOWERS: She had several lymph nodes, so she did meet GELF criteria by having more than 3 lymph nodes that were bigger than 3 centimeters and had several lymph nodes that were in the 3- to 4-cm range now at this point.
DR LOVE: So Julie, again, not a rare situation. What would you be thinking about?
DR VOSE: First of all, this brings up an issue of doing scans in asymptomatic patients. And we would never even do any of those scans until the patient has symptoms. That’s a long discussion, a long appointment about really aggressive therapy versus less aggressive therapy at that point. And so somebody of that age, you potentially would still want to consider transplantation as an option. So that would be a more aggressive side of what I would discuss with her. On the less aggressive side, some of the other treatment options for her as far as bendamustine/rituximab as an option, many different agents would be an option at that point. And at this juncture, you have to really discuss very aggressive nature versus not aggressive nature with the patient, I think.
DR LOVE: What about that idea, Chris, of aggressive treatment for her?
DR FLOWERS: Yes. I think that it was appropriate to consider. And we discussed that as well, the role of autologous stem cell transplant and potentially the long-term role of allogeneic stem cell transplant. She was still very active, working. She was a healthcare professional and was very busy and didn’t want to spend time away from work and particularly the time that it was going to take to go through an autologous transplant.
DR LOVE: Jon?
DR FRIEDBERG: I would have strongly recommended an autologous approach one year after R-CHOP. The median progression-free survival after R-CHOP chemotherapy is in the 4- to 5-year range. And she had evidence of disease progression within a year of obtaining a documented complete remission. And I would have predicted the biology of her disease to be poor.
I find it fascinating that she’s been able to remain under control for 7 years with single-agent rituximab after such a rapid progression after R-CHOP. I don’t think that’s necessarily the common scenario. But at her age, still, given at least demonstration of relative refractoriness to standard doses of chemotherapy, my vote would be more toward an aggressive approach, like Julie was suggesting.
DR LOVE: Mike?
DR WILLIAMS: So she’s relatively young. I agree with the comments about a little surprising she did as well as she did with rituximab. So she responded to second-line rituximab, did well with maintenance and has been off it now for 3 years?
DR FLOWERS: Correct.
DR WILLIAMS: And so she wants to do something, but she doesn’t want to do a big thing. So the question is, what might you do to bridge her over to such time as I think she may well need a transplant or something more aggressive? So given that rituximab response and the time off therapy, I would have the long discussion about the options, but I would consider just treating her with rituximab again and putting her back on maintenance again, given she had a good response. She’s had a good time off therapy. She may well respond again. So that might be a start, and at least you’d give her a chance to show you whether she’s going to be able to get a good response to probably the simplest and safest therapy she could get right now and probably avoid a cytotoxic.
If she doesn’t respond well to that, then I think she’s kind of declared that she’s going to have to do something more. And I think that rather than just add in any subsequent therapy I give, if it’s going to be bendamustine or whatever, I would be thinking we’re moving toward a transplant with her, that we’re going to induce her and get her off to that kind of hopefully more durable remetive therapy.
DR LOVE: Chris?
DR FLOWERS: She did undergo typing for an allogeneic stem cell transplant that could have been reserved for a later date. We also talked related to Mike’s points about the role of returning to single-agent rituximab. I, like Jonathan and others, I was quite surprised that she went that long without additional therapy, relapsing that soon after R-CHOP. And that’s what brought autologous stem cell transplant into the picture.
Having been on years of maintenance therapy with rituximab, she really was not interested in the maintenance approach as part of that and viewed single-agent rituximab as single-agent rituximab plus maintenance. And so after more discussion, what she elected to do was to go on to receive radioimmunotherapy. So she got a single test dose at that time and then a treatment dose of radioimmunotherapy, had a good response and has remained in remission from that time until now.
DR LOVE: And how long has that been?
DR FLOWERS: And that’s been about a year and a half now. Close to 2 years now.
DR LOVE: Mike?
DR WILLIAMS: Yes. I’d just be interested in Julie’s comments on that. So it certainly — again, it proves to be a very active agent, but for somebody you’re thinking about taking to a transplant…I know there’s data that you can collect stem cells without any problem, but I just wonder, was that a concern, if you think you’re ultimately going to get her there?
DR VOSE: So the data is, if a patient’s more than 6 months beyond getting radioimmunotherapy, it’s probably okay as far as collecting the cells. Of course, you never know what’s really going to happen, if they’re going to respond or not. But — so if she’s a year and a half out, she’d probably be okay. The issue is, do you want to — and you’ve already decided this, because you said — do you want to do an autotransplant in somebody who’s had multiple, multiple therapies? There’s lots of information now in multiple cytotoxic therapies that autotransplant doesn’t work. But in a patient who’s had lots of rituximab and radioimmunotherapy, there’s not that much data. So…don’t know.
DR EVENS: But Chris, you wouldn’t say auto is off the table, would you, down the road?
DR FLOWERS: In our discussion, really, part of the decision to move to radioimmunotherapy was that autotransplant would unlikely be part of her regimen in the future, given that this would occur some point down the line when she would need more cytotoxic therapy for autotransplant. And now we’re talking about something really in the closer to the fourth line, although Julie brings up good points, that this is now considering radioimmunotherapy and rituximab as her second- and third-line therapies. It’s hard to know what that means. But I would very rarely consider autologous transplant for a follicular lymphoma patient in the fourth-line setting.