Panobinostat Plus Velcade and Dexamethasone Shows Promise in Heavily Pretreated Myeloma

The experimental drug panobinostat (LBH-589) in combination with Velcade® (bortezomib) and dexamethasone is effective for heavily pretreated multiple myeloma, according to the final results from a phase 2 clinical trial published in Blood.

Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. Patients with multiple myeloma who have become refractory—or resistant—to the drugs Revlimid® (lenalidomide) and Velcade® (bortezomib) have limited treatment options. There is no standard treatment for these patients and they typically have a poor prognosis, with a median overall survival of 9 months.

Panobinostat is a drug that belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division and cause cell death. It is being studied in myeloma as well as other blood cancers and solid tumors. Early studies have shown that panobinostat in combination with Velcade more effectively kills myeloma cells than either drug alone.

PANORAMA 2 is a phase 2 trial of panobinostat in combination with Velcade and dexamethasone to treat patients with relapsed and Velcade-refractory multiple myeloma. The study included 55 heavily pretreated patients with relapsed/refractory multiple myeloma. The patients had received a median of four prior lines of therapy, including a median of two Velcade-based regimens. All patients were refractory to their last Velcade regimen and 82 percent were refractory to the combination of Velcade and dexamethasone.

Treatment with panobinostat occurred in two phases. The first phase consisted of eight 3-week treatment cycles with panobinostat/Velcade/dexamethasone. Patients who responded or demonstrated stable disease proceeded to the second phase, which consisted of six-week cycles of treatment with the combination. Patients were treated until disease progression or until they could no longer tolerate the therapy.

Overall, 34.5 percent of patients responded to the treatment: 1 patient achieved a near-complete response and 18 patients achieved a partial response. Another 36 percent of patients (10 patients) had stable disease. The clinical benefit rate was 52.7 percent. The median time to response was 1.4 months and median duration of response was 6 months.

The most common severe side effects were thrombocytopenia (low platelet counts), fatigue, and diarrhea. Only one patient had grade 3 peripheral neuropathy.

The researchers concluded that “panobinostat, when combined with Velcade and dexamethasone, can recapture responses in heavily pretreated, Velcade-refractory multiple myeloma patients.”

Reference:

Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013; 122(14):2331-2337.

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