Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

Anita Kumar, Carla Casulo, Joachim Yahalom, Heiko Schöder, Paul M Barr, Philip Caron, April Chiu, Louis S Constine, Pamela Drullinsky, Jonathan W Friedberg, John F Gerecitano, Audrey Hamilton, Paul A Hamlin, Steven M Horwitz, Alexandra G Jacob, Matthew J Matasar, Gianna N McArthur, Susan J McCall, Alison J Moskowitz, Ariela Noy, Maria L Palomba, Carol S Portlock, David J Straus, Nicholas VanderEls, Stephanie L Verwys, Joanna Yang, Anas Younes, Andrew D Zelenetz, Zhigang Zhang, Craig H Moskowitz, Anita Kumar, Carla Casulo, Joachim Yahalom, Heiko Schöder, Paul M Barr, Philip Caron, April Chiu, Louis S Constine, Pamela Drullinsky, Jonathan W Friedberg, John F Gerecitano, Audrey Hamilton, Paul A Hamlin, Steven M Horwitz, Alexandra G Jacob, Matthew J Matasar, Gianna N McArthur, Susan J McCall, Alison J Moskowitz, Ariela Noy, Maria L Palomba, Carol S Portlock, David J Straus, Nicholas VanderEls, Stephanie L Verwys, Joanna Yang, Anas Younes, Andrew D Zelenetz, Zhigang Zhang, Craig H Moskowitz

Abstract

This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451.

© 2016 by The American Society of Hematology.

Figures

Figure 1
Figure 1
Treatment schema.
Figure 2
Figure 2
Clinical trial flowchart.
Figure 3
Figure 3
Trend in DLCO(Hb) and FVC during the treatment program. (A) Mean DLCO(Hb) at baseline, pre-ISRT, post-ISRT, and 12 months posttreatment are 91% (n = 30), 82% (n = 29), 92% (n = 23), and 98% (n = 15), respectively. (B) Trend in FVC during treatment program. Mean FVC at baseline, pre-ISRT, post-ISRT, and 12 months posttreatment are 91% (n = 30), 97% (n = 28), 99% (n = 22), and 106% (n = 15), respectively.
Figure 4
Figure 4
PFS by intent to treat (N = 30) with median follow up of 18.8 months.

Source: PubMed

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