Selecting Therapy for Relapsed-Refractory DLBCL

Nathan H. Fowler, MD:When patients relapse either after frontline therapy or after autologous stem cell transplant, I generally think of patients in 2 main buckets. The first bucket is patients who have a great performance status, whose blood counts are pretty good and who have good organ function. These are patients who are great candidates for an aggressive approach when they relapse after transplant or after frontline therapy. For those patients, I still use combination approaches, and that would mean some combination chemotherapy that hopefully uses different drugs from the ones they were exposed to either with the transplant or in the frontline setting.

I’ll provide an example. If a patient received CHOP [cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone] chemotherapy in the frontline and then received ICE [ifosfamide, carboplatin, etoposide] chemotherapy, and ICE [ifosfamide, carboplatin, etoposide] didn’t work, I would switch to DHAP [dexamethasone, high-dose cytarabine, cisplatin], or I would switch to gemcitabine-oxaliplatin, or I might switch to a methotrexate-based regimen. I’m thinking that this patient has a good performance status. They’re still very healthy. And so what is a combination chemotherapy regimen that could potentially work, that will kill these cells that didn’t respond to traditional chemotherapy? Ideally, if they’re pretransplant, I’m trying to get them to a place of good remission, so I can get them to autologous transplant. If they’re relapsing after an autologous transplant, I’m trying to control that disease to get them to a place where they might tolerate allogeneic transplant or potentially go on to some maintenance therapy or something else to try to control their disease long-term.

The other bucket of patients are patients who either are too old—I hate to use the wordold, because I thinkoldis just age. I should say patients who have a poor performance status, are bed-bound, and kidney function that isn’t very good, and maybe they have difficulties with heart function. These are patients who, even if I can get them into a remission, probably are not going to tolerate a stem cell transplant. For those patients, I’m looking for something that is not too toxic and is going to give me a long a progression-free survival.

Then I’m thinking about novel targeted drugs, potentially immune-based drugs or biological drugs, that patients can tolerate, will not affect organ function, and can give me a long progression-free survival. I’m really trying to maximize their quality of life. What we don’t ever want to do is have a treatment that’s worse than the disease. For a patient I can’t give aggressive chemotherapy to, I’m really looking at something that is mild and is going to control that disease for as long as possible.

Transcript edited for clarity.