Brentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma?

Older patients with Hodgkin lymphoma (HL) often don’t tolerate standard chemotherapy regimens and have worse outcomes compared with younger patients. While previous studies have indicated that single-agent brentuximab vedotin is safe and effective for these patients, other trials have suggested that its efficacy may be improved by the addition of dacarbazine or bendamustine.

In a recent phase II, frontline, open-label study, Christopher A. Yasenchak, MD, from the Willamette Valley Cancer Institute and Research Center/US Oncology Research in Springfield, Oregon, and colleagues examined the efficacy and durability of brentuximab vedotin as a single-agent and in combination with dacarbazine or bendamustine in patients with HL ≥60 years old. Dr. Yasenchak presented the results of the study at the 2015 ASH Annual Meeting.

The researchers plan to enroll 70 treatment-naïve patients who will be randomized to receive:

  • Brentuximab vedotin 1.8 mg/kg administered every 3 weeks for up to 12 cycles (n=30)
  • Brentuximab vedotin 1.8 mg/kg administered every 3 weeks for up to 12 cycles plus dacarbazine 375 mg/m2 (n=20)
  • Brentuximab vedotin 1.8 mg/kg administered every 3 weeks for up to 12 cycles plus bendamustine 70 mg/m2 or 90 mg/m2 for up to 6 cycles (n=20)

Patients were included in the study if they had an Eastern Cooperative Oncology Group performance status <3 and were ineligible for or had declined conventional treatment.

The median age was 76 years (range = 62-92 years), 55 percent were male, and 65 percent had stage 3-4 disease. The majority (70%) were ineligible for conventional chemotherapy, while 30 percent had declined conventional treatment.

At the time of data presentation, 60 patients had been treated: 27 with brentuximab vedotin monotherapy, 22 with brentuximab vedotin plus dacarbazine, and 11 with brentuximab vedotin plus bendamustine. Of these, 24, 21, and 9 patients, respectively, were evaluable for efficacy.

A total of 45 patients have discontinued therapy due to adverse events (AEs), progressive disease after complete or partial remission, or other reasons. Fifteen patients are still receiving treatment, Dr. Yasenchak noted.

Treatment-related grade ≥3 AEs were reported in 43 percent of all patients receiving treatment in the study; 22 percent of these AEs were serious and no patient had died within 30 days of last dose. Grade ≥3 AEs occurred with the following frequencies:

  • Brentuximab vedotin: 13 (48%)
  • Brentuximab vedotin + dacarbazine: 8 (36%)
  • Brentuximab vedotin + bendamustine: 5 (45%)

Patients in the dacarbazine group received a median of 11.5 treatment cycles, those in the monotherapy group had received a median of eight cycles, and the median duration of treatment had not yet been defined for the brentuximab vedotin plus bendamustine cohort.

As seen in TABLE, for patients treated with brentuximab vedotin plus dacarbazine, the overall response rate (ORR; the study’s primary endpoint) was 100 percent, with 62 percent of patients achieving complete remission (CR). The median PFS in this cohort had not been reached.

Similarly, among patients treated with brentuximab vedotin plus bendamustine, the ORR was 100 percent, but with a higher CR rate of 78 percent. Notably, for patients treated with the bendamustine combination the starting dose was reduced from 90 to 70 mg/m2 to improve tolerability after the first 10 patients were enrolled.

With an ORR of 100 percent in both combination regimens, it appears that these regimens have “promise as front-line therapies in this vulnerable patient population,” the authors concluded. “Ongoing follow-up will define durability, and ultimately the potential role of these combinations as standard options for elderly patients with HL.”


Reference

Yasenchak CA, Forero-Torres A, Cline-Burkhardt VJM, et al. Brentuximab vedotin in combination with dacarbazine or bendamustine for frontline treatment of Hodgkin lymphoma in patients aged 60 years and above: interim results of a multi-cohort phase 2 study. Abstract #587. Presented at the 2015 ASH Annual Meeting, December 7, 2015; Orlando, Florida.

TABLE. Efficacy Results Among Evaluable Patient
Brentuximab vedotin monotherapy (n=26) Brentuximab vedotin + dacarbazine (n=21) Brentuximab vedotin + bendamustine (n=9)*
ORR, n (%) 24 (92) 21 (100) 9 (100)
CR rate, n (%) 19 (73) 13 (62) 7 (78)
Median PFS, months (range) 10.5 (2.6-22.3) Not reached (4.2-14.3) Not reached (1.2-6.2)
Median observation time, months (range) 20.4 (4.6-30.4) 9.8 (4.9-14.3) 3.6 (2.3-7.0)
Patients with progression or death, n (%) 16 (62) 3 (14) 1 (11)
*Enrollment ongoing

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