Novel Therapies in Hodgkin Lymphoma Coming to Clinics

Sandra Kear
Published: Saturday, Feb 21, 2015

Anas Younes, MD

Anas Younes, MD

Although treatments and cure rates have increased significantly over the past 60 years for patients with Hodgkin lymphoma (HL), it is crucial that practitioners stay up-to-date on research that can affect outcomes for their patients with this uncommon form of cancer. Anas Younes, MD, professor of medicine, chief, lymphoma service, Memorial Sloan Kettering Cancer Center, presented recent data at the 19th Annual International Congress on Hematologic Malignancies (February 20-21, 2015) regarding therapies in clinical trials and others that are now available for use.

Recent Treatments

According to Younes, recent treatment for favorable early-stage HL has involved 2 cycles of ABVD plus 20 Gy of radiation therapy (XRT) and for unfavorable early-stage HL, 4 cycles of ABVD plus 30 Gy of XRT has been the standard. Bulky mediastinal disease has traditionally been treated with 6 cycles of ABVD plus 30 Gy of XRT. Another option included 2 cycles of BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone) and 2 cycles of ABVD plus 30 Gy of XRT.

In the past, a radiation-free approach has included 6 cycles of ABVD with no XRT. Younes maintained that an increasingly PET-guided approach is being used in treatment decisions and that overall survival (OS) and progression-free survival (PFS) have shown some similarities with XRT compared with non-XRT approaches.

The RAPID trial,1 which looked at patients with stage IA or IIA prognosis, included 3 cycles of ABVD followed by PET. Patients who were PET negative were randomized to no treatment and observation or given involved field radiation therapy (IFRT). Patients who were PET positive were given 1 cycle of ABVD plus IFRT. Overall survival and PFS were similar between the XRT and non-XRT groups (PFS: 94.5% vs 90.8% respectively; hazard ratio [HR] 1.51; P = .23. OS: 97.1% vs 99.5% respectively; HR 0.15; P = .07).

For patients with advanced-stage disease, 6 cycles of ABVD has been the standard of care. If the patient experiences a complete remission or a PET-negative partial response, observation is recommended, according to Younes, but if the patient is PET positive with a residual mass, a biopsy may be performed, and if the biopsy is positive then therapy may be changed to an ifosfamide, carboplatin, vinblastine (ICE) along with ASCT or an equivalent salvage regimen. Some studies have shown positive results when treating patients who are PET positive, who have smaller lesions, without the use of radiation, Younes said; however, traditionally this approach is not used with patients with advanced-stage disease.

Patients who relapse after ABVD, may be given a platinum-based regimen. If no response occurs, a gemcitabine-based regimen could then be administered, and if response does not follow this regimen (transplant ineligible), then a third-line treatment could include brentuximab vedotin or an investigational agent, according to Younes.

Brentuximab vedotin

Brentuximab is an antibody drug conjugate (ADC) that combines the anti-CD30 antibody with a cytotoxic tubulin-disrupting agent. The drug is approved by the FDA for the treatment of patients with HL after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not candidates for ASCT. Brentuximab has demonstrated substantial activity and low toxicity in patients with refractory or chemoinsensitive HL.2,3 “The goal is to achieve a response regardless of the regimen,” Younes said. “And if you achieve a good response, the standard of care is still to take the patient to autologous transplant, and if you do that, you can cure approximately 50% to 60% of patients, regardless of the salvage regimen.”

When a patient fails after autologous transplant, the expected OS is usually about 2.4 months. “That is why these patients represent an urgent unmet medical need. “That is why all of us are involved in trying to develop novel agents to try to prolong the survival of these patients,” Younes said.

In the phase II pivotal trial of brentuximab, 102 patients with relapsed/refractory HL post ASCT benefited and had disease reductions. Seventy-five percent of patients achieved objective response (95% confidence interval [CI], 64.9%, 82.6%), with 34 patients experiencing a complete response (CR) (95% CI, 25.2%, 44.4%).3

Complete responses were also prolonged. At the March 2014 data cutoff, the median duration of response for the 34 patients who achieved a CR had not been reached (95% CI: 20.5 mos, —).4 Therefore the question, according to Younes, is, ‘Should these patients be given immediate transplant, or is there room for observation?’

“Some of these patients are expected to have long-term remission,” Younes said. He prefers the observation approach for these patients who achieve CR. If they progress, he said, “you can retreat again with brentuximab vedotin.”

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