Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma.

PURPOSE: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550). METHODS: Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m2 IV, days 1 and 8), vinorelbine (20 mg/m2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m2, days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS: Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION: Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.

Rapid and sustained response of an intra- and extracranial large cell lymphoma mass to liposomal intrathecal Ara-C and R-MegaCEOP systemic chemotherapy.

Prognosis of patients suffering from secondary central nervous system (CNS) lymphoma is dismal. Intracranial spread of a lymphoma arising in adjacent extranodal tissues is a rare event. A 32-year-old patient was diagnosed with progressive diffuse large B-cell lymphoma (DLBCL) with extra- and intracranial localization. He complained of headache, left diplopia, marked rigidity of the neck muscles, and difficulty in swallowing and articulating words, caused by bilateral palsy of the XII cranial nerve. Computed tomography (CT) and positron emission tomography (PET) scans showed disease localizations in the occipital-cervical soft tissue, and cerebellar parenchyma. Due to the severity of the clinical picture, high-dose dexamethasone was immediately administered. Mild improvement was observed during the first 2 days of treatment, but dramatic reduction of symptoms and nerve palsy was documented only in the 48 h after the first intrathecal administration of liposomal Ara-C. Systemic R-MegaCEOP chemotherapy was started 7 days later. Concomitant intrathecal liposomal Ara-C injections were continued for a total of nine administrations during the eight cycles of immunochemotherapy without any toxicity observed. Interim and post-therapy PET showed complete resolution of radionuclide accumulation in the involved sites. Consolidation radiotherapy (36 Gy) was administered in involved areas after the completion of the immunochemotherapy program. At the time of writing, no cumulative neurotoxicity is evident at follow-up of 17 months from diagnosis and 9 months after the overall therapeutic program has been accomplished.