Brentuximab vedotun was recently approved by the FDA for transplant-ineligible and transplant-failing Hodgkin lymphoma (HL) patients. Three abstracts at the ASH meeting regarding this agent are noteworthy.
Younes et al (Abstract 955) combined brentuximab vedotin with ABVD or AVD in patients with advanced stage, untreated HL. Interim data on the first 31 patients were presented, and there are mixed messages. This was a planned ABVD study, but seven of the first 19 patients had significant pulmonary toxicity that included interstitial lung disease leading to a protocol amendment eliminating bleomycin.
Thus far all evaluable patients are in complete remission, which is encouraging. However, there needs to be extreme caution when combining brentuximab vedotin with any agent that has the propensity to cause pulmonary toxicity, including gemcitabine. The role of brentuximab vedotin as part of combined modality (chemotherapy and radiation) approaches for HL clearly needs to be studied
There were two complementary presentations—one by Chen et al (Abstract 664) and a second by Illidge et al (Abstract 3091) that evaluated brentuximab vedotin as a bridge to a reduced-intensity allogeneic stem cell transplant.
Combining the data from both abstracts, a total of 23 patients received a transplant after achieving a partial or complete response to brentuximab vedotin. The median number of doses of brentuximab vedotin administered was nine. The one-year progression-free survival rate was greater than 90% in both cohorts. This is a very reasonable approach for any patient with a matched related or unrelated donor who has a least a six-month median duration of response from their autotransplant and when brentuximab vedotin is administered as the first treatment after the failed autotransplant.
The number of doses of brentuximab vedotin necessary prior to the reduced-intensity allogeneic stem cell transplant is debatable, but in our practice we administer four, and if the disease is FDG-PET negative, we administer another two and then admit the patient for the transplant.
Early-State HL Update
Radiation therapy is standard in the management of early stage HL, since PFS is improved in nearly every study that incorporated it, but overall survival is the same when comparing chemotherapy alone vs. combined-modality therapy (CMT) programs. There is, therefore, much controversy about whether it is needed all of the time, sometimes, or never. In an update of the ECOG NCIC randomized study (Abstract 590), Meyer reported the final analysis of this study with 11.3 years of follow-up.
The results demonstrated an inferior survival for patients receiving CMT. It must be remembered that the type of radiation therapy used in the study is antiquated; extended-field radiation therapy at this dose and schedule is no longer used. The German HL Study Group (GHSG) has reported that in early-stage HL treated with CMT, PFS ranges from 91% to 96%, depending on prognostic factors.
At this point either full-course ABVD or modern CMT are equivalent alternatives for early stage HL, and phase III studies are nearly completed to determine which treatment strategy will ultimately become standard of care.
Advance-Stage HL (ASHL)
Lastly, Hodgkin Lymphoma Study” (Abstract 589). In this study more than 1,000 patients were randomly assigned to receive either eight or six doses of escalated BEACOPP or eight doses of BEACOPP-14. The five-year freedom from treatment failure rate was 84, 89, and 85 percent, respectively; in the opinion of the GHSG, six doses of escalated BEACOPP should be considered standard of care for ASHL.
A word of caution here, that with modern PET-adapted approaches using as little as two cycles of escalated BEACOPP combined with ABVD, the results are quite similar, with less short-term and potentially less long-term toxicity. Studies are underway comparing these approaches.
BMTCTN DLBCL Phase III Trial
Vose et al (Abstract 661) reported the results of the BMTCTN (Blood and Marrow Transplant Clinical Trials Network) high-priority randomized phase III trial of Bexxar-BEAM vs. Rituximab-BEAM followed by autologous stem cell transplantation (ASCT) for patients with relapsed diffuse large B cell lymphoma (DLBCL).
At a median follow-up of two years, there was no difference in PFS or overall survival, with approximately 50% of patients cured on both arms. This was an unexpected finding since phase II data were very promising for the Bexxar-BEAM approach. It appears that the use of radioimmunotherapy as part of transplant-conditioning regimens in lymphoma is not a reasonable treatment approach.