Abstract
Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common form of Non-Hodgkin's Lymphoma (NHL). Aggressive DLBCL is challenging to treat because many patients do not respond to first-line treatment. Rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine (RHYPERCVAD) is commonly used to treat acute lymphoid leukemia and some aggressive lymphomas. At our institution, we occasionally use this regimen in patients with refractory and aggressive DLBCL, and we sought to perform a retrospective cohort study to analyze these treatment outcomes.
Methods: This IRB-approved study involved first identifying a larger list of patients who had received treatment plans incorporating the chemotherapies of RHYPERCVAD. We then identified those patients with newly diagnosed DLBCL or B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt's Lymphoma, based on WHO classification 2008 or 2016, depending on when these patients were diagnosed. Advanced stage disease (either stage 3 or 4) and no prior treatment with a different regimen (</= 1 cycle) was part of the inclusion criteria. Response was assessed by imaging with CT scan or PET/CT. Data was then collected by chart review from electronic medical records and old paper charts including notes, imaging and pathology results. Primary outcomes including complete response rate, progression free survival (PFS) and overall survival (OS) were studied.
Results: After the above inclusion criteria were met, a total of 10 patient charts were reviewed. Demographics of the patients selected included the following: a mean age of 47.4 years, a median age was 47.5 years, with a range of 30 to 64. Out of the 10 patients, 6 patients had a diagnosis of DLBCL and 4 patients had a diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt's Lymphoma. Of note, 9 out of 10 patients had stage 4 disease and 1 had stage IIIB disease. The revised International prognostic index (r-IPI) ranged between 2 to 5. 40% of patients had a score of 2, 30 % of patients had a score of 3 and 20% of patients had a score of 4. In patients who had the diagnosis of DLBCL, 3 had germinal center B (GCB) like disease and 3 had non-GCB (nGCB) disease based on Hans classification. Complete response (CR) was achieved in 7 out of 10 patients (CR rate 70%). 3 out of 10 patients (30%) progressed on treatment. None of the patients who had a complete response relapsed. 2 of the patients who had a complete response passed away from causes which were not related to disease or treatment. 2 patients who had poor performance status passed away from septic shock within 4 months of starting treatment. The median follow up for patients who are still alive was 54 months. 3-year PFS was 60%. 3-year OS was 60%. None of the patients who had complete remission relapsed. Mean and median PFS were 38.4 months and 41 months, respectively.
Conclusion: RHYPERCVAD is a high-intensity regimen and the benefits of using this therapy need to be weighed against the risks of life-threatening infections, bleeding, and other complications. This regimen should be avoided in those who are older (>60 years old), have a poor performance status, or have significant comorbidities given the toxicities associated with the regimen. 2 of our patients with poor performance status passed away as a result of the toxicity associated with this therapy. CR rate observed in our sample was higher than what is reported with standard therapy for similar patients having advanced disease. OS, however, was similar to standard treatment. None of our patients had relapsed with a median follow up of 54 months for those who are still alive. We believe that this regimen could be used in the right patient population; younger individuals with good performance status who have advanced and aggressive DLBCL. This is because of the superior rates of CR and lower relapse rates that have been noted in other studies as well. In this population, a large randomized trial should compare the standard treatment with this regimen and look at the long-term outcomes. Our study has the limitations of being a single center retrospective study with a small patient population.
Disclosures
Seiter:Incyte: Honoraria, Research Funding; Novartis: Honoraria; Alexion Pharmaceuticals: Honoraria; Bristol Myers Squibb: Research Funding; Takeda: Research Funding; GlycoMimetics: Research Funding; Rafael Pharmaceuticals: Research Funding; Theradex: Research Funding; Jazz Pharmaceuticals: Research Funding; Sellas Life Sciences: Research Funding.
