Brentuximab vedotin may have curative effect in relapsed, refractory Hodgkin lymphoma
A subgroup of patients with relapsed and refractory Hodgkin lymphoma who experienced a complete response with brentuximab vedotin have achieved disease control for more than 5 years and may be cured of disease, according to phase 2 study results.
“Hodgkin lymphoma is a very treatable malignancy that tends to show up more frequently in younger patients, and is often cured with chemotherapy and radiation programs,” Joseph M. Connors, MD, FRCPC, clinical professor of medicine at University of British Columbia and clinical director of the Centre for Lymphoma Cancer at BC Cancer Agency, told HemOnc Today. “In about 20% of patients, it is not cured, and the disease will threaten their lives. Before brentuximab vedotin [Adcetris, Seattle Genetics] was developed, we hadn’t found a new agent that had much potency or effectiveness for these patients in several decades.”
Joseph M. Connors
Patients with Hodgkin lymphoma who relapse or progress following an autologous hematopoietic stem cell transplantation typically experience poor outcomes, with median OS estimates between 1 year and 2 years.
Connors and colleagues enrolled 102 patients with relapsed or refractory Hodgkin lymphoma following a failed autologous hematopoietic stem cell transplantation. The researchers assigned patients to 1.8 mg/kg IV brentuximab vedotin every 3 weeks for up to 16 cycles.
Median follow-up for all enrolled patients was 35.1 months (range, 1.8-72.9).
The cohort had a median OS of 40.5 months (95% CI, 28.7-61.9) and a median PFS of 9.3 months (95% CI, 7.1-12.2). The 5-year OS estimate was 41% (95% CI, 31-51) and 5-year PFS estimate was 22% (95% CI, 13-31).
At the time of the analysis, 15 patients remained on study and in remission, and had not proceeded to any new therapy other than allogeneic HSCT after a median observation time of 69.5 months (range, 66.5-72.9).
Seventy-five percent of patients (n = 77) received at least one anticancer therapy after discontinuing brentuximab vedotin (median, n = 3; range, 1-10), including multiagent therapy (n = 44), single-agent therapy (n = 42) and HSCT (n = 22).
Thirteen patients were retreated with brentuximab vedotin as a single agent (n = 10) or multiagent (n = 3).
Median duration of response has not been reached in a subgroup of 34 patients who achieved a complete response (95% CI, 20.5-not reached). This subgroup had an estimated 5-year OS rate of 64% (95% CI, 48-80) and PFS rate of 52% (95% CI, 34-69).
Thirteen of the 15 patients in remission at study closure achieved a complete response as best response (median treatment cycles, 14); the remaining two patients had a partial response (median treatment cycles, 6.5).
Nine of these patients received no further cancer treatment, with the remaining four proceeding to consolidative HSCT.
Peripheral neuropathy served as the most common adverse event among the entire study cohort (55%; n = 56). Eighty-eight percent (n = 49) of these patients experienced resolution (n = 41) or improvement (n = 8) of peripheral neuropathy symptoms; all patients with unresolved peripheral neuropathy had grade 1 or grade 2 symptoms.
“It’s striking to see that a fraction of patients sustained their complete responses,” Connors said. “It is not unreasonable to hope that some of those patients were cured by brentuximab vedotin. Before this agent came along, we didn’t have a way of doing that.” – by Cameron Kelsall
For more information:
Joseph M. Connors, MD, FRCPC, can be reached at firstname.lastname@example.org.
Disclosure: Seattle Genetics and Millennium funded this research. Connors reports institutional research funding from Seattle Genetics and Takeda. Please see the full study for a list of all other researchers’ relevant financial disclosures.