The targeted therapy brentuximab vedotin may have cured some Hodgkin lymphoma patients whose disease has persisted despite receiving previous therapies, according to a new study.
“This is the first study in relapsed or refractory Hodgkin lymphoma that shows 5-year survival results from a single drug. This study can also change the paradigm of practice and that some patients with relapsed or refractory Hodgkin lymphoma can be cured with brentuximab vedotin,” noted, lead author Robert Chen, MD, of the City of Hope National Medical Center, Duarte, Calif. The authors published the final data from brentuximab vedotin monotherapy pivotal phase II clinical trial in relapsed or refractory classical Hodgkin lymphoma (doi:10.1182/blood-2016-02-699850).
Brentuximab Vedotin Results
The single-arm trial, which supported the FDA approval in 2011 of brentuximab vedotin for this indication, was conducted in 102 relapsed or refractory classical Hodgkin lymphoma patients who had previously received an autologous stem cell transplant to assess the efficacy and safety of single-agent brentuximab vedotin. Enrolled patients had received a median of more than three prior chemotherapy regimens.
At 5 years, the 102 patients had an estimated overall survival (OS) rate of 41 percent and progression-free survival (PFS) rate of 22 percent. The 34 patients who achieved a complete response (CR) to brentuximab vedotin had estimated OS and PFS rates of 64 percent and 52 percent, respectively. The median OS and PFS were not reached in CR patients.
Of the 34 (38%) patients who achieved CR, 13 patients have remained disease-free for more than 5 years and may be cured. Of these 13 patients, four patients received consolidative hematopoietic allogeneic-SCT and nine patients (9% of all enrolled patients) remain in sustained CR without receiving any further anti-cancer therapy after treatment with brentuximab vedotin.
The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea. Treatment emergent peripheral neuropathy was experienced by 56 patients (55%). Eighty-eight percent of these patients experienced improvement of their peripheral neuropathy symptoms, including 73 percent with complete resolution.
“After 5 years of follow-up, 41 percent of the patients are alive. Also, 15 patients are currently alive without any evidence of lymphoma from the initial 102 patients, and for the 33 percent of patients that achieved CR, 52 percent of them are alive 5 years out without any evidence of lymphoma,” said Chen.
He noted that “prior to this drug, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant. The median survival of the patients on brentuximab vedotin monotherapy in this pivotal phase II trial exceeds these historic figures.”
Chen added that “brentuximab vedotin is now the standard of care for patients who relapse after stem cell transplantation or two lines of therapy. For the patients who are able to achieve CR on brentuximab vedotin, this drug can cure some Hodgkin lymphoma patients.”
Hodgkin Lymphoma Studies
Brentuximab vedotin is an antibody-drug conjugate directed to CD30, a key driver of classical Hodgkin lymphoma tumor pathogenesis. The drug is being evaluated broadly in more than 70 ongoing clinical trials, including the phase III ALCANZA trial and two additional phase III studies, ECHELON-1 in frontline classical Hodgkin lymphoma, and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.
The drug via IV injection has received approval from the FDA for three indications:
- Regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
- Regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation.
- Accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Chen said the message for practicing oncologists is that “this study shows that there are durable responses to brentuximab vedotin even 5 years out from treatment, and that the drug is very tolerable with largely reversible peripheral neuropathy side effects. The fact that we can report such durable results after 5 years is incredible. Each day that these individuals continue to spend with their loved ones is a testament to the strides our community is making in understanding and beating treatment-resistant lymphomas.”
Mark L. Fuerst is a contributing writer.