BV+AVD had statistically higher rates of neutropenia (58% vs 45%), constipation (42% vs 37%), vomiting (33% vs 28%), peripheral neuropathy (26% vs 13%), abdominal pain (21% vs 10%), and stomatitis (21% vs 16%) compared with ABVD. The BV+AVD group also had more overall hospitalizations (37%) compared with ABVD (28%). Most deaths during the clinical trial were related to neutropenia in the BV+AVD group and to pulmonary-related toxicity in the ABVD group.

These data suggest that BV+AVD may be considered a preferable first-line therapy over the traditional regimen of ABVD. Yet several additional points that should be considered. It is important to note, for example, that although replacing bleomycin with BV led to less pulmonary toxicity and improved mPFS, the rate of other toxicities increased.

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One of the key toxicities reported in this group was neutropenia, which was limited by prophylactic use of granulocyte colony–stimulating factor in the clinical trial. Peripheral neuropathy was also more common in the BV group, though was reported as reversible in 67% of patients. Treatment cost should also be taken into account, as BV is significantly more expensive than bleomycin.

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Close to 30 clinical trials are currently or are planning to evaluate BV in multiple malignancies.6 Similarly to ECHELON-1, ECHELON-2 (ClinicalTrials.gov Identifier: NCT01777152) is evaluating how BV performs in another CD30-positive lymphoma. Researchers are comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with BV plus CHP as a first-line treatment in patients with CD30-positive mature T-cell lymphomas. It will be important to see whether ECHELON-2 yields similarly positive results to ECHELON-1.

References

  1. Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Hellman S. Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. Cancer. 1993;71(6):2062-71.
  2. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7(11):1630-6.
  3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059-67. doi: 10.1200/JCO.2013.54.8800
  4. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or stage IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331-44. doi: 10.1056/NEJMoa1708984
  5. Adcetris prescribing information. Seattle Genetics website. http://www.seattlegenetics.com/application/files/1915/2157/0234/adcetris_USPI.pdf. Updated March 2018. Accessed April 2018.
  6. ClinicalTrials.gov. ECHELON-2: a comparison of brentuximab vedotin and CHP with standard-of-care CHOP in the treatment of patients with CD30-positive mature t-cell lymphomas (ECHELON-2). NCT01777152. https://clinicaltrials.gov/ct2/show/NCT01777152. Accessed April 2018.

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Hematologic Cancers Lymphoma