ONCAlert | Upfront Therapy for mRCC

Second-Line Therapy for GVHD

Targeted Oncology
Published Online:12:00 PM, Mon August 26, 2019

Claudio Anasetti, MD: There is a possibility that patients do not improve within the first 3 weeks. They may actually worsen after3 days, or not improve after 7 days, or worsen at any time after that. We define those patients as glucocorticoid-refractory. In that case, at the first clinical observation of refractoriness, we determine that the patient needs a second agent. My impression is that the early treatment versus waiting longer is beneficial for patients with steroid-refractory graft-versus-host disease [GVHD]. There may be other patients who have an initial response, for whom we are continuing the taper of the prednisone and they actually have a flare. These patients are defined as steroid-dependent. Although the flare may occur at a low dose of prednisone, invariably the outcome of such patients is so poor that I routinely start a salvage second-line agent immediately—at the time that I observe the first flare on the prednisone taper. Those patients are said to be affected by steroid-dependent GVHD.

Involvement with GVHD of visceral organ is associated with a worse prognosis. Overall, grade 3 graft-versus-host disease is associated with about half the rate of response of overall grade 2 graft-versus-host disease, which is milder and usually does not involve the visceral organ as much.

For primary therapy, we use glucocorticoids, methylprednisolone, prednisone, or analogues. But once these agents fail, a variety of agents have been used. Until recently, there was no FDA-approved agent. The most commonly used agent in the community is mycophenolate mofetil. Personally, I prefer sirolimus. But recently, I started to use sirolimus for GVHD prevention, and this precludes my use of the same drug for treatment. Fortunately, the recent trial and approval of ruxolitinib for the treatment of acute GVHD that is resistant or dependent on glucocorticoids has changed our approach. That has become our standard of care as second-line therapy.

Transcript edited for clarity.

Claudio Anasetti, MD: There is a possibility that patients do not improve within the first 3 weeks. They may actually worsen after3 days, or not improve after 7 days, or worsen at any time after that. We define those patients as glucocorticoid-refractory. In that case, at the first clinical observation of refractoriness, we determine that the patient needs a second agent. My impression is that the early treatment versus waiting longer is beneficial for patients with steroid-refractory graft-versus-host disease [GVHD]. There may be other patients who have an initial response, for whom we are continuing the taper of the prednisone and they actually have a flare. These patients are defined as steroid-dependent. Although the flare may occur at a low dose of prednisone, invariably the outcome of such patients is so poor that I routinely start a salvage second-line agent immediately—at the time that I observe the first flare on the prednisone taper. Those patients are said to be affected by steroid-dependent GVHD.

Involvement with GVHD of visceral organ is associated with a worse prognosis. Overall, grade 3 graft-versus-host disease is associated with about half the rate of response of overall grade 2 graft-versus-host disease, which is milder and usually does not involve the visceral organ as much.

For primary therapy, we use glucocorticoids, methylprednisolone, prednisone, or analogues. But once these agents fail, a variety of agents have been used. Until recently, there was no FDA-approved agent. The most commonly used agent in the community is mycophenolate mofetil. Personally, I prefer sirolimus. But recently, I started to use sirolimus for GVHD prevention, and this precludes my use of the same drug for treatment. Fortunately, the recent trial and approval of ruxolitinib for the treatment of acute GVHD that is resistant or dependent on glucocorticoids has changed our approach. That has become our standard of care as second-line therapy.

Transcript edited for clarity.
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