Brentuximab Vedotin Leads to Long-Term Remissions in Patients with Relapsed/Refractory Hodgkin Lymphoma

In 2011, the U.S. Food and Drug Administration approved the CD30 antibody-drug conjugate brentuximab vedotin for the treatment of patients with Hodgkin lymphoma (HL) whose disease has progressed after autologous hematopoietic cell transplantation (AHCT) or two prior therapies. Approval was based on the results of an international, open-label, phase II study of 102 patients with HL, in which the complete response (CR) rate was 34 percent (95% CI 25.2-44.4) and the objective response rate (ORR) was 75 percent (95% CI 64.9-82.6).1

In a study published in Blood, Robert Chen, MD, from the City of Hope National Medical Center in Duarte, California, and colleagues report the five-year, end-of-study results of this pivotal trial, finding that brentuximab vedotin led to an estimated five-year overall survival (OS) rate of 41 percent and a progression-free survival (PFS) rate of 22 percent.2

“In the pre-brentuximab vedotin era, options were limited and outcomes were poor for HL patients who relapsed or progressed after AHCT, with median OS ranging from 10.5 to 27.6 months,” Dr. Chen and colleague wrote. “Given that the historical outcomes are poor for HL patients who relapse after AHCT, these results provide a new perspective on prognosis for this patient population in the brentuximab vedotin era.”

The trial included 102 patients with relapsed/refractory HL (median age = 31 years; range = 15-77 years) who were enrolled at 25 centers in the United States, Canada, and Europe between February and August 2009. Patients were heavily pretreated, with a median number of prior regiments (other than AHCT) of 3.5 (range = 1-13 regimens). Sixty-six percent of patients received prior radiation therapy, and all patients underwent AHCT. The median time to relapse after AHCT was 6.7 months (range = 0-131 months), and the majority of patients (71%) experienced relapse within a year of undergoing AHCT.

Patients received 1.8 mg/kg of brentuximab vedotin administered intravenously over 30 minutes once every three weeks for up to 16 treatment cycles.

One-third of all patients (n=34/102) achieved a CR, with a median response duration that was not reached (95% CI 20.5-not reached). Within this group, the estimated five-year OS and PFS rates were 64 percent (95% CI 48-80) and 52 percent (95% CI 34-69), respectively.

Of the 34 patients who achieved a CR, six underwent consolidative allogeneic HCT (alloHCT) as the next therapy after brentuximab vedotin. These six patients had estimated five-year OS and PFS rates of 83 percent (95% CI 54-100) and 67 percent (95% CI 29-100), compared with 60 percent (95% CI 41-78) and 48 percent (95% CI 28-68), respectively, among the 28 patients who did not undergo HCT.

At the time of study closure, approximately five years from the last patient’s end-of-treatment visit, 15 patients remained on the study and in remission without salvage therapy other than alloHCT. Thirteen of these patients achieved CR (having received a median of 14 cycles of treatment), and two achieved a partial response (PR; having received a median of 6.5 cycles).

For these 13 patients:

  • median OS was 40.5 months (95% CI 28.7-61.9)
  • median PFS was 9.3 months (95% CI 7.1-12.2)
  • estimated 5-year OS was 41% (95% CI 31-51)
  • estimated 5-year PFS rates was 22% (95% CI 13-31)

A majority of the study patients (75%; n=77) received at least one anti-cancer therapy following brentuximab vedotin: 45 received multi-agent therapy, 42 received single-agent therapy, and 22 underwent HCT (8 of whom received consolidative allogeneic HCT).

Thirteen of these 77 patients received retreatment with brentuximab vedotin (10 as single-agent, 3 as multi-agent), and six were treated with a PD-1 pathway inhibitor (5 as single-agent, 1 as combination therapy).

Of the 13 complete responders who remained in remission at five-year follow-up, four underwent consolidative alloHCT, while nine (26% of all CR patients) received no further treatment. “The notion that alloHCT with reduced-intensity conditioning is the only option for long-term disease control is challenged,” the authors noted. “Nine percent (n=9/102) of the enrolled study population has achieved long-term remission exceeding five years in response to single-agent brentuximab vedotin without any additional therapy.”

The most commonly reported adverse event associated with cumulative exposure to brentuximab vedotin was peripheral neuropathy (PN; 55%; n=56). Most of the patients experiencing PN (88%; n=49) had resolution or improvement, with 73 percent (n=41) reporting complete resolution and 14 percent (n=8) reporting some improvement at last follow-up. Overall, Dr. Chen and colleagues found “the reported toxicities [to be] manageable.”

“These results provide a new perspective on prognosis for this patient population,” the authors concluded. “Among patients with relapsed/refractory HL, a substantial fraction of patients who obtained CR with single-agent brentuximab vedotin have achieved long-term disease control and may be potentially cured.”

Though the authors noted that treatment with brentuximab vedotin improved upon the historically poor outcomes for patients with relapsed/refractory HL, there was no comparator arm in this trial. Also, though the five-year OS and PFS rates were high for patients who underwent consolidative alloHCT, further studies are needed to identify which patients could benefit from this therapy after receiving brentuximab vedotin.


References

  1. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183-89.
  2. Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016. [Epub ahead of print]

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