DR FRIEDBERG: So this is a 65-year-old physician who was recently referred to me for a consultation regarding management of CLL. He was diagnosed way back in 2000 when he presented with a lymph node that was enlarged in his neck, and biopsy showed small lymphocytic lymphoma. He was followed for 6 years, and then the lymphadenopathy became bulky and he got fludarabine and rituximab as an up-front treatment. He did well but after the treatment he had autoimmune hemolytic anemia develop.

In 2008 he had, again, evidence of disease progression, and he got FCR treatment. And then in 2010, there was a recurrence of autoimmune hemolytic anemia, and he got cyclophosphamide/rituximab and prednisone.

One year later, he had worsening pancytopenia. And a bone marrow biopsy was done that did show on FISH evaluation a small percent of his cells that had acquired the deletion of chromosome 17p. He had hemolysis as well at that time, and he got bendamustine and rituximab, which resulted in profound neutropenia and a prolonged hospital stay.

And since then, he’d been followed. He had a hospitalization for disseminated varicella zoster. He was maintained on immunoglobulin. And over the last year or so, he really developed progressive significant bulky lymphadenopathy, splenomegaly, very large retroperitoneal mass and he was sent to me for treatment options.

DR LOVE: So Julie, again, just maybe we can start out talking about outside a protocol setting.

DR VOSE: Off of a clinical trial, I probably would have discussed lenalidomide, low dose, with this patient. We had a clinical trial where we added ofatumumab to lenalidomide and had some quite good responses even in very heavily pretreated patients. And you have to start very low on the lenalidomide dose.

DR LOVE: Mike?

DR WILLIAMS: So yes, these are common scenarios. And I guess the question is, just taking a step back, are the mechanism of his cytopenias, is it marrow involvement? Is it hypoplasia from his prior therapy, which is probably most likely? Is there a degree of hypersplenism? And is there bulky adenopathy, especially in the setting of his 17p deletion? Is there any evidence of Richter’s transformation accounting for any of this that would shift our therapy more toward a lymphoma-like regimen?

If that occurred, our approach is usually to use EPOCH, especially if we think that he’ll be able to get enough marrow response that he’ll recover from that. Outside of that, if it’s really just progressive refractory CLL/SLL, then I agree. I mean, I think given his cytopenias and his prior therapy, a noncytotoxic approach is where we’re going to have to go. So I would think short courses of corticosteroids plus ofatumumab. I think low-dose lenalidomide is also a good option. And I think in this case, getting him toward a clinical trial with one of the newer agents, perhaps one of the B-cell receptor pathway inhibitors, that show good activity in the 17p setting, would be a good approach.

DR LOVE: So do you want to say what happened with him?

DR FRIEDBERG: Right. So basically, our discussion outside of clinical trial, I brought up both the ofatumumab and the lenalidomide as options. I think with the deletion of chromosome 17, I probably would have favored lenalidomide, but I think both of those were reasonable choices.

However, we were fortunate to have a clinical trial of a BTK inhibitor. This is AVL-292. It’s a very similar molecule to ibrutinib. It’s designed to be a little bit more potent and in our experience in early Phase II development, it really has a very similar response profile to ibrutinib.

He was enrolled on that and had a very rapid response with a brief period of lymphocytosis. Then his other blood counts have improved and, after about 4 cycles of treatment, he’s in a near CR, feeling very well.

DR LOVE: Andy?

DR EVENS: So Jonathan, not knowing how long this is going to last, is this something to circle back on in terms of allogeneic transplant?

DR FRIEDBERG: Right. I think absolutely. I think in his case, we sent HLA typing, and we plan to have him meet with the team to discuss whether or not transplantation is an option, because you’re exactly right. We don’t know how long this is going to last. If we extrapolate from some of the ibrutinib data that was presented at Lugano, even in deletion of chromosome 17, there does appear to be a subset of patients who have very prolonged responses.

Now, he’s only 65 years old. The question is, is prolonged 1 or 2 years or is it a lifetime? I don’t think we have any idea yet.