Bendamustine Demonstrates Promising Activity in Post-Brentuximab Failure Hodgkin Lymphoma Patients Who Had Also Failed a Prior Autologous HCT and Facilitates Successful Bridging to Allogeneic HCT

BACKGROUND:

Hodgkin's lymphoma (HL), although considered a curable neoplasm in adults, could be associated with a very poor prognosis when refractory to primary induction therapy or when it relapses within 12 months from an autologous stem cells transplant (auto-HCT).The optimal treatment of patients with heavily pretreated/refractory HL is controversial. Brentuximabvedotin(Bv) is an active single agent in this context; unfortunately, there are nowell establishedtherapies when patients fail to respond or progress afterBv. Encouraging results were recently described with checkpoint inhibitors. Similarly, data pertaining to efficacy ofbendamustine(Benda) shows encouraging activity in various refractory lymphomas.

PATIENTS AND METHODS:

We included in this study adult patients with HL who relapsed post auto-HCT and were refractory to or progressed after salvageBvand were treated withBenda as salvage therapy with an intention to proceed with anallo-HCT. This study was conducted in two major centersin Lebanon,the American university of Beirut Medical Center (AUBMC) andMakasseduniversity hospital. We identified 12 eligible cases.The primary study endpoint was objective response rate (ORR). The secondary endpoint evaluated successful rate of bridging into anallo-HCT.

RESULTS:

The median follow-up times from Auto-HCT and from Benda salvage were 35 (14-59) and 10 (4-35) months, respectively. The median age of patients was 27 years (17-54).All patients hadBvas salvage therapy post Auto-HCT, and all of them progressed after a median of 4 (3-6) cycles.Clinical characteristics are outlined in Table 1. Patients received a median of 6 cycles (2-8) of Benda.The treatment was well tolerated, with rather infrequent adverse events and transient and manageable toxicities.

The ORR was 75%, in 9 of 12 patients, with 43% obtaining a complete response. Eventually, 6 of 9 proceeded toallo-HCT using a matched related donor, and the remaining 3 patients are planned forallo-HCT. Only one patient died from disease progression after 24 months postallo-HCT. Two of 3 patients who progressed followingbendareceived salvage therapy withnivolumaband are being planned forhaplo-identical transplant while the third one is being planned for therapy withnivolumab. From the initiation ofbenda, the median duration of response for the 9 patients was 10 months (4-29); all these patients had maintained a continuous response at the last follow-up examination.

CONCLUSION:

Notwithstanding the limitations associated with our analysis, namely a small sample size and its retrospective nature, these results suggest a role forbendamustinein postBvfailures.These findings also provide the basis to evaluate the concept of Benda as a bridge toallo-HCT in a large prospective study.

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