Adcetris and PET-Adapted Salvage Therapy Effective in Relapsed/Refractory Hodgkin’s Lymphoma

Posted on January 16th, 2014 by

Patients with relapsed/refractory Hodgkin’s lymphoma who achieve complete responses after treatment with Adcetris® (brentuximab vedotin) can skip more toxic salvage therapy and proceed straight to transplant, according to the results of a study presented at the 2013 International Symposium on Hodgkin Lymphoma in Cologne, Germany.

Hodgkin’s lymphoma is a cancer of the lymph system. It typically begins in the lymph nodes in one region of the body and then spreads throughout the lymph system. Hodgkin’s lymphoma that returns after prior therapy is considered relapsed, or recurrent, disease. Hodgkin’s lymphoma that does not respond to standard therapies is considered refractory disease. Patients with relapsed or refractory Hodgkin’s lymphoma may be treated with high doses of chemotherapy and stem cell transplant. If the cancer returns after a stem cell transplant, treatment options are limited.

Pre-transplant positron-emission tomography (PET) normalization is one of the strongest predictors of outcome following autologous stem cell transplant (ASCT) in patients with this stage of disease. This is often achieved with a regimen called ICE (ifosfamide, carboplatin, etoposide), which is highly toxic.

Adcetris is a targeted agent that targets a protein known as CD30, which is present on Hodgkin lymphoma cells as well as cells from other cancers. Once Adcetris enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E. Adcetris has shown significant clinical activity and a manageable safety profile in patients with relapsed or refractory Hodgkin’s lymphoma.

In this phase II study, researchers sought to incorporate Adcetris in salvage therapy with the goal of normalizing the PET and eliminating the more toxic chemotherapy. The study included 46 patients with relapsed/refractory Hodgkin’s lymphoma. Patients received two cycles of weekly Adcetris followed by PET imaging. Patients who achieved normalization of PET (≤ Deauville 2) proceeded to stem cell transplant while those with PET scores ≥ Deauville 3 received two cycles of augmented ICE (double doses of ifosphamide and etoposide). The primary endpoint was complete response rate after Adcetris with or without augmented ICE. Although the weekly schedule is uncommon, phase I data have shown promise with more intensive treatment.

Adcetris was associated with high response rates. The complete response rate was 80 percent after Adcetris (with or without ICE). Thirty percent of patients were able to avoid ICE salvage therapy and proceed straight to transplant.

Only eight patients did not achieve a complete response, and of these, two proceeded directly to autologous stem cell transplant (based on very good, though not complete, responses), five had PET-negative disease and received radiotherapy followed by stem cell transplant, and one received additional chemotherapy.

Adverse events related to Adcetris included neuropathy and rash, which were primarily mild and manageable. Grade 2 neuropathy occurred in only 15 percent of patients, and grade 2/3 rash, which responded well to steroids, was observed in 18 percent.

Because of the promising results, the researchers have initiated an expansion study, which will include an additional 20 patients who will receive weekly Adcetris for three cycles (as opposed to the two cycles in the initial protocol). PET-negative patients will then proceed to stem cell transplant, while PET-positive patients will receive augmented ICE for two cycles.

Reference:

Moskowitz AJ, Schoder H, Gerecitano J, et al: PET adapted sequential salvage therapy with brentuximab vedotin and augmented ICE for transplant eligible patients with relapsed and refractory Hodgkin lymphoma. 9th International Symposium on Hodgkin Lymphoma. Abstract T128. Presented October 15, 2013.

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Tags: Advanced Stage Hodgkin's Lymphoma, Hodgkin's Lymphoma, News, Progressive Relapsed Hodgkin's Lymphoma

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