Brentuximab and PET-Adapted Salvage May Eliminate Toxic Chemotherapy for Refractory Hodgkin Lymphoma


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Alison J. Moskowitz, MD

Relapsed and refractory transplant-eligible Hodgkin lymphoma patients who achieve complete responses after treatment with brentuximab vedotin (Adcetris) can often avoid more toxic salvage chemotherapy, according to investigators from Memorial Sloan-Kettering Cancer Center, New York.

Positron-emission tomography (PET)-adapted sequential salvage therapy after treatment with brentuximab allowed 30% of patients to avoid chemotherapy with ICE (ifosfamide, carboplatin, etoposide) and proceed straight to transplant, said Alison J. Moskowitz, MD, a hematologist/oncologist at Memorial Sloan-Kettering, who presented the study at the 9th International Symposium on Hodgkin Lymphoma in Cologne, Germany.1

Study Rationale

The phase II study was based on the following rationale: Current salvage regimens such as ICE are quite toxic, but brentuximab is well tolerated and highly active in Hodgkin lymphoma in patients for whom autologous stem cell transplantation fails, and pretransplant PET normalization is a strong predictor of outcome following stem cell transplant.

“We have previously shown that the outcome for patients with normal pretransplant PET is excellent, regardless of whether PET normalization is achieved following ICE therapy alone or ICE followed by additional non–cross-resistant chemotherapy. Due to its high efficacy and excellent tolerability in [autologous stem cell transplant] failures, we aimed to determine whether brentuximab could replace ICE salvage therapy or increase the rate of PET normalization through PET-adapted sequential administration with augmented ICE,” Dr. Moskowitz said.

“In other words, our idea was to incorporate brentuximab in salvage therapy with the goal of normalizing the PET. We hoped that by doing so we might be able to eliminate the more toxic chemotherapy, when patients normalize on brentuximab alone,” Dr. Moskowitz explained in an interview with The ASCO Post.

Weekly Dosing With Brentuximab

The phase II study enrolled 46 patients with relapsed/refractory Hodgkin lymphoma. Patients received two cycles of weekly brentuximab given at 1.2 mg/kg 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 (ie, double doses of ifosphamide and etoposide). The primary endpoint was complete response rate after brentuximab with or without augmented ICE.

Dr. Moskowitz noted that the weekly schedule is not commonly given, but phase I data have suggested responses might occur earlier with more intensive treatment.

High Response Rates Achieved

The complete response rate was 80% after brentuximab (with or without ICE), and 30% of patients were able to avoid ICE salvage therapy, Dr. Moskowitz reported.

“Of 40 evaluable patients, 36 have completed [autologous stem cell transplant], 3 will undergo [stem cell transplant] shortly, and one remains on treatment for persistent disease,” she said.

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

Expansion Study

The investigators have initiated an expansion study in which an additional 20 patients will receive weekly brentuximab for three cycles (not two, as in the initial protocol).

“So far, we have seen that 30% of patients become PET-negative with brentuximab alone, but many patients do achieve a very good response after two cycles, and we believe that if they received a third cycle, they may become PET-negative,” Dr. Moskowitz explained.  

PET-negative patients will proceed to stem cell transplant, while PET-positive patients will receive augmented ICE for two cycles. In a second PET assessment, those who are still PET-positive will receive further treatment while the PET-negative patients will undergo stem cell transplant. ■

Disclosure: Research support was provided by Seattle Genetics

Reference

1. 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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