Patients with Relapsed/Refractory Hodgkin's Lymphoma Benefit from VTEPA Salvage Regimen
SAN DIEGO, CA—A retrospective review reported on during the 53rd American Society of Hematology Annual Meeting and Exposition found vinorelbine, paclitaxel, etoposide, cisplatin and cytarabine (VTEPA) to be a promising salvage regimen in patients with relapsed/refractory Hodgkin's lymphoma. However, patients with refractory diffuse large B-cell lymphoma (DLBCL) had “exceedingly poor” outcomes in comparison, according to investigators from Winship Cancer Institute, Emory University School of Medicine, who said there remains a “great need for novel agents” for this population.
Historically, patients with relapsed DLBCL and Hodgkin's lymphoma have a high cure rate when treated with a salvage regimen followed by high-dose chemotherapy and autologous stem cell transplant (ASCT). In contrast, those who relapse early following upfront chemotherapy or fail to respond to salvage treatment have a poor overall response rate (ORR) with additional salvage regimens and a poor prognosis, even when consolidated with ASCT, Rajni Sinha, MD, and colleagues noted.
The investigators designed a regimen to address the lack of a standard third-line therapy for Hodgkin's lymphoma or DLBCL. In a previously reported Phase 1 study, the VTEPA regimen—vinorelbine 30mg/m2 + paclitaxel 175mg/m2 Day 1, etoposide 100mg/m2 + cisplatin 20mg/m2 Days 2–5, and cytarabine 2,000mg/m2 Days 4–5—was safe, with an ORR of 33% after one cycle.
To examine the effectiveness of VTEPA, Dr. Sinha and colleagues conducted an Institutional Review Board-approved retrospective review of consecutive cases of patients with relapsed/refractory DLBCL and Hodgkin's lymphoma in the institution's database from 1999–2011. All patients had evidence of primary refractory disease or stable or progressive disease following first-line salvage therapy. International Working Group Criteria were used to assess response following salvage VTEPA therapy. Patients who responded had proceeded to ASCT. Using the Kaplan-Meier method, survival curves were constructed for those with DLBCL and Hodgkin's lymphoma and compared with the log-rank test.
A total of 74 patients were included in the retrospective review, 44 with DLBCL and 30 with Hodgkin's lymphoma. Median age at diagnosis was 49 years (range 20–68) for those with DLBCL and 30 years (range 18–63) for Hodgkin's lymphoma. In the DLBCL group, 75% of patients had primary refractory disease and 25%, relapsed disease; 73% were stage III/IV at diagnosis. Among those with Hodgkin's lymphoma, 66% had primary refractory disease and 33%, relapsed disease; 60% were diagnosed with stage III/IV disease.
Patients had received a median of two prior therapies (range 1–4). Of patients with DLBCL, 70% had received prior salvage therapy with rituximab + ifosfamide, carboplatin, and etoposide (ICE) and 16% received other salvage regimens; 32 patients had received one cycle of rituximab + VTEPA and 12 patients, two cycles. Among those with Hodgkin lymphoma, 63% had received prior salvage therapy with ICE and 13% with other regimens; 16 patients received one cycle of VTEPA, 13 received two cycles, and one patient, three cycles.
There were 70 patients (43 with DLBCL and 27 with Hodgkin's lymphoma) evaluable for response. The ORR for patients with DLBCL was 44% (9% CR and 35% PR); for those with Hodgkin's lymphoma, ORR was 70% (26% CR and 44% PR, P=0.04). Four patients with DLBCL had treatment-related mortality.
Of the 74 patients, 34 had ≥2x106 CD34+ cells/kg collected; three patients had inadequate stem cell collection. In another 23 patients, collection was not attempted, and 14 had stem cells collected prior to treatment with rituximab with or without VTEPA. Planned ASCT was conducted in 37 patients (47%) and four underwent allogeneic transplantation.
At two years, progression-free survival (PFS) was 68% for patients with Hodgkin lymphoma and 49% for patients with DLBCL ( P<0.001, See Figure 1). Overall survival (OS) was significantly higher at two years for those with Hodgkin lymphoma, 79% vs 41% for patients with DLBCL (P<0.001, See Figure 2).
The most commonly reported grade 3/4 adverse events were pancytopenia (97%), nausea/vomiting (58%), fatigue (30%), infectious complications (26%), diarrhea (24%), electrolyte imbalance (19%), and mucositis (16%).
Dr. Sinha concluded that treatment with VTEPA for patients with heavily pretreated relapsed/refractory Hodgkin's lymphoma and DLBCL is feasible, with manageable adverse events and high ORR, and permits ASCT in nearly half of patients. “There is a great need for novel agents to aid DLBCL patients who are chemotherapy and rituximab refractory,” according to the researchers in a statement at their poster presentation.