Real World Efficacy of the Novel Chemo-Free Combination of Brentuximab Vedotin Plus Nivolumab (BvNivo) in Patients with Relapsed/Refractory Hodgkin Lymphoma. Single Center Experience

Introduction

Up to 30% of patients with Hodgkin lymphoma (HL) are refractory to induction chemotherapy or will relapse. Platinum or gemcitabine-based salvage chemotherapy followed by autologous stem cell transplantation (ASCT) results in a durable remission in about 50% of these patients. Brentuximab vedotin (Bv) and nivolumab (Nivo) are non-chemotherapy agents with novel mechanisms of action, are well-tolerated, and due to their significant efficacy, have been approved as single agents in relapsed/refractory (r/r) HL. Recent studies suggest that the combination of BvNivo is safe and may have significant synergistic tumor activity in r/rHL. We therefore evaluated this combination in a similar patient population.

Methods

In this retrospective study, we evaluated the efficacy of BvNivo in patients diagnosed at our Institution with r/r HL and who had either failed conventional salvage chemotherapy prior to ASCT, had relapsed post-ASCT, or had refused or were ineligible to receive chemotherapy as salvage therapy. Bv at 1.8 mg/kg IV and nivolumab at a 240 mg IV flat dose were received every 3 weeks. There were no prespecified cycles of treatment, the number was determined according to response and the subsequent consolidative strategy that was regarded most appropriate for the patient, based on clinical judgment and patient's preference. Descriptive statistics were used to present patient characteristics and immune-related adverse events (imAEs). The primary endpoints were objective response rate (ORR) and complete metabolic response (CRm) according to Lugano 2014 classification. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results

Thirteen patients (11 male) were identified from our database with HL and treated with BvNivo. Median age at diagnosis was 25 years (range, 17-31). The majority (11 patients) had advanced stage disease, 6 with bulky mediastinal disease. All patients had received induction therapy with ABVD. Nine patients (69%) had primary induction failure (PIF), 4 of whom subsequently failed ASCT. At the time of BvNivo treatment: 5 patients (4 with PIF) had failed a median of 2 (range, 1-4) prior salvage therapies; 4 patients had relapsed at 5, 6 14, and 34 months, respectively, post-ASCT; 4 patients were ineligible (1 patient) or refused (3 patients) ASCT.

The 5 patients who had failed prior salvage therapies received a median of 3 (range, 2-4) cycles of BvNivo. The ORR and CRm rate were both 100%. All patients proceeded to ASCT and were all progression-free +5 - +20 months post-ASCT. Of the 4 patients that relapsed post-ASCT the ORR/CRm rate were both 50%. The 2 patients that achieved mCR completed 6 cycles of BvNivo and were progression-free at +8 and +10 months, respectively. One patient continues on maintenance nivolumab. Both patients were eligible for allogeneic SCT but declined. The 2 non-responding patients had stable disease but discontinued after 5 and 14 cycles, due to progression, and remain alive at 8 and 15 months, respectively.

Three patients refused chemotherapy; one had relapse 11 months after ABVD, received 3 cycles of BvNivo, achieved CRm for 9 months and remains alive at 24 months; one patient was PIF, achieved PRm (Deauville 4) with 4 cycles of BvNivo, was consolidated with radiotherapy to the mediastinum, achieved CRm and remains progression-free at +4 months; one patient had relapse at 6 months after ABVD, received 6 cycles of BvNivo, achieved CRm, and was consolidated with involved node radiotherapy and maintenance nivolumab, and remains progression-free at +20 months. One patient ineligible for ASCT was a PIF, failed 2 lines of salvage therapy and demonstrated stable disease to BvNivo which was maintained for 18 cycles, subsequently progressed and remains alive at 36 months. Three patients presented with imAEs, one with grade 2 hepatotoxicity, one with grade 2 adrenalitis, and one with grade 3 dermatitis, all managed and resolved with corticosteroids, allowing continuation of treatment.

Conclusions

Overall, despite the small patient sample and the heterogenous disease status, BvNivo demonstrated promising ORR and CRm rates of 77% and 69%, respectively, in a mostly heavily pre-treated patient population. Furthermore, the observed durable responses suggest that the combination of BvNivo should be further explored in r/r HL as a salvage regimen for patients eligible or ineligible for ASCT or after failure of ASCT.

No relevant conflicts of interest to declare.